Blood Safety Transcripts

U.S. PUBLIC HEALTH SERVICE
ADVISORY COMMITTEE ON BLOOD

SAFETY & AVAILABILITY

EIGHTH MEETING

THE RESERVE CAPACITY OF THE NATION'S

BLOOD SUPPLY

Day One

Thursday, April 29, 1999

8:00 a.m.

Holiday Inn Bethesda

8120 Wisconsin Avenue

Bethesda, Maryland 20814

C O N T E N T S

AGENDA ITEM: Page

Call to Order

Conflict of Interest Declaration 3

Comments by Surgeon General David

Satcher 7

Dr. Harvey Klein

National Institutes of Health 28

Current Trends in Blood Donation

and Utilization:

Marian Sullivan, National Blood

Data Resource Center 128

Frequency of Blood Donation and

Reserve Capacity of the Blood Supply:

Dr. George Schreiber

Westat, Inc. 153

Use of Incentives to Increase

Blood Donation:

Dr. Alan Williams

American Red Cross 203

Demographic Correlates of the

Incidence of Viral Infection

among Blood Donors:

Dr. Michael Busch

Blood Centers of the Pacific 233

Techniques for Increasing Yield

of Blood per Donation:

Dr. Ronald Gilcher

Oklahoma Blood Institute 264

P R O C E E D I N G S

DR. NIGHTINGALE: I'm Stephen Nightingale and this is the Eighth Meeting of the Advisory Committee on Blood Safety and Availability. While you are taking your seats, I will begin this meeting by reading what Dr. Caplan has previously described as the "ritualistic reading of the ethics statement." I would remind Dr. Caplan that ritual and ethics have a long and productive history of working together.

"The following announcement is made as part of the public record to preclude even the appearance of a conflict of interest at this meeting. General applicability has been approved for all committee members.

This means that unless a particular matter is brought before this committee that deals with a specific product or firm, it has been determined that all interests reported by the committee members represent no potential conflict of interest when evaluated against the agenda. In particular, as specified in Title 18, U.S. Code 208(b)(2), a special Government employee, which all committee members are, may participate in a matter of general applicability, for example, advising the Government about its policies relating to the Hepatitis C epidemic, even if they are presently employed or have the prospect of being employed by an entity, including themselves, if they are self-employed, that might be affected by a decision of the committee, provided that the matter will not have a special or distinct effect on the employee or employer other than as part of the class."

"The example given in five, Code of Federal Regulations, 2640.203, which implements Title 18, U.S. Code 208(b)(2) is as follows: A chemist employed by a major pharmaceutical company has been appointed to serve on an advisory committee established to develop recommendations for new standards for AIDS vaccine trials involving human subjects. Even though the chemist's employer is in the process of developing an experimental AIDS vaccine and therefore will be affected by the new standards, the chemist may participate in formulating the advisory committee's recommendations. The chemist's employer will be affected by the new standards only as part of the class of all pharmaceutical companies or other research entities that are attempting to develop an AIDS vaccine."

"In the event the discussions involve a specific product or a specific firm for which a member has a financial interest, that member should exclude him or herself from the discussion and that exclusion will be noted in the public record. With respect to other meeting participants, we ask, in the interest of fairness, that they disclose any current or previous financial arrangements with any specific product or specific firm upon which they plan to comment."

I would then call the role to determine that we have a quorum to begin the meeting with. I see that we do. Mr. Allen is present. Dr. Gilcher is present. Dr. Gomperts is present. Dr. Caplan is present. Dr. Haas is present. Dr. Hoots is present. Dr. Kuhn is present. Dr. Goosby is present. Dr. McCurdy is present. Dr. Epstein and Dr. Chamberland are both present. I am not sure, as the parliamentarian, if they qualify for the quorum, but they are nevertheless present, as is Dr. Goosby and Dr. McCurdy.

Ms. O'Connor is present. Dr. Penner is present. Captain Rutherford is present, Dr. Secundy is present, and Mr. Walsh is present.

Dr. Caplan.

DR. CAPLAN: The committee will recall, at our last session, we decided to start down the road of a very important issue for the country and that is the supply side of the nation's blood supply, and we've set up a meeting for the next two days, which is going to get us into the nuances, and twists and turns of this important question.

Dr. David Satcher, the assistant secretary for Health, and Surgeon General of the United States has kindly agreed to take time away from his busy schedule to offer some lead-off comments on this issue, and I am just going to turn the floor over to him.

DR. SATCHER: Thank you very much, Dr. Caplan, and members of the committee, good morning. I'm delighted to be able to join you, and, again, want to express our appreciation for all of your very outstanding efforts to help insure the safety and availability of our blood supply.

I have to say this. As most of you know, I spend most of my time traveling, and one of the things I do as Surgeon General is I speak a lot, and I guess I have become well known for the Surgeon General's prescriptions, and I can tell you that that breakfast over there doesn't comply.

[Laughter.]

DR. SATCHER: So I am a little embarrassed. I have on here, physical activity, five days a week, 30 minutes a day, and then the second thing is eat at least five servings of fruits and vegetables per day. So we have to do something about what we serve.

There are two topics that I want to discuss, briefly, looking back and looking forward, and I'm delighted that you're going to be spending most of your time looking forward.

I do want to comment that our Hepatitis C look-back effort, as you know, is now well underway. The recommendations that you made in January of this year have been unanimously endorsed by the Department's Blood Safety Committee and accepted by the Secretary and myself. Food and Drug Administration has announced that a revised guidance to industry on Hepatitis C look-back will be forthcoming in early May.

This guidance will incorporate your recommendations without changing nay of the previous look-back efforts or the timetable in which they will occur.

We haven't talked much, I don't think here, about what's happening with the targeted look-back and I wanted to make a couple comments about that.

In February of this year, America's blood centers reported that 51 out of 58 of their members had initiated look-back programs, and that 34 percent had completed their components of the look-back. On March 19th, the American Red Cross informed us that they were on schedule to complete their look-back efforts within the time allotted.

Then last week, we received a report from the American Association of Blood Banks on the status of their look-back efforts and they reported that 29 percent of the 147 blood collection facilities that they surveyed had completed their component of the look-back. Overall, they report that the task of the blood collection facilities, which is to identify potentially infectious units of blood, and communicate this information to the transfusion services, appears to be at least half completed.

They also report that the 393 transfusion services they surveyed have identified more than half of the recipients of the units so far reported to them, and they've completed the notification process for more than half of those which they have identified.

So I think the targeted look-back is going well, and as I said earlier, the changes that you recommended would be implemented.

Next week, the Centers For Disease Control and Prevention will hold a press briefing, here, in Washington, at the National Press Club, to publicize its public outreach campaign of general notification about Hepatitis C.

This campaign, which Dr. Margoles described to you in January, will initially target prior transfusion recipients, many of whom cannot be reached through the direct notification program.

It will be followed by a major effort directed toward all people at risk for Hepatitis C virus infection, and as you know from Dr. Margoles' presentation, CDC has already embarked upon a vigorous campaign that would help professionals, and help providers who will be interacting with this process.

So I would now like to turn from looking back to looking forward. We can hope that there will never be another threat to blood safety that would compare with the threats of the HIV and hepatitis threat, but we cannot deny that there might be, and we have to be ready for it.

As you know, we need to anticipate, for example, that it may be necessary to defer, at least temporarily, some portion of our current donor pool, and we need to plan how to do this in a way that minimizes its impact on those who depend upon blood for their health and safety, and even their lives.

I think it's fair to say that we should never permit ourselves to be in a position, as some have suggested, we may have been in the past, where we would feel obligated, by medical necessity, to release a unit of blood if we had serious doubts about its safety.

Our contingency plans need to be made, and not after a threat appears on the horizon. Over the next two days, you will be asked to review the state of our reserve capacity of blood and to make recommendations for how we might strengthen it before, and not after circumstances require that we make use of this capacity, and we look forward with great interest to reviewing the results of your deliberation.

At future meetings we would encourage you to explore the potential impact of the dramatic economic changes in health care financing on the safety and availability of blood, and these changes are, indeed, dramatic, just looking at the way they are impacting our academic health centers, for example, and hospitals, in general.

We, as a society, have determined that our blood supply must be unequivocally safe. The technology to insure unequivocal safety, at least for the pathogens that we know, is developing rapidly.

At the same time, the cost of this technology is substantial, and there is concern whether the current system of reimbursement will allow funds to become available to pay for these advancements in a timely manner.

However, we should never permit ourselves, I think, to be in a position, as some have suggested that we may have been in the past, where we might permit a delay in the introduction of a needed safeguard to the blood supply simply because funding had not been arranged to support it, and I think we can avoid being in that position again.

So today appears to be a point of transition for the committee, in a way, because much of your efforts have been devoted to advising us about how best to look back, and even though we continue to look back, we hope that you can summon an even greater effort in advising us how best to look forward, and, in particular, how to prevent threats to blood safety and availability, rather than how to deal with them once they have occurred.

Certainly in this country, prevention is a less glamorous activity than repair, but is no less difficult and is no less important, and I hope that that will be the legacy of our work together.

Let me just close by sharing with you what has evolved as our three priorities for the Office of the Surgeon General and in the Office of the Assistant Secretary for Health. We have tried, because I am only the second person, Julie Richman, being the other one, to serve as both assistant secretary for Health and Surgeon General.

We have tried very hard to integrate these two functions in a way, perhaps, that they have never been integrated before, and one of the aspects of that is agreeing upon priorities for both, that are common, and we have sort of settled on three areas, the first one being working to move the nation toward a balanced community health system, balanced in the sense that it balances health promotion, disease prevention, early detection, and universal access to care.

You may say, well, where are we now? We are a long ways from that. We spend $1.5 trillion a year for health care in this country, about 1 percent of that amount for population-based prevention, and a lot of unnecessary pain and suffering takes place because of that.

So we are trying very hard to, in so many ways, work within the system, and in the grassroots community, to move in that direction.

We have pointed out that a balanced community health system will help to do several things, among them, help to assure that every child has the optimal chance for a healthy start in life. It will promote healthy life styles, and often, when we talk about healthy life styles we think about the personal responsibility, such as physical activity and nutrition, avoiding toxins like tobacco and illicit drugs, responsible sexual behavior, and those are all personal responsibilities.

But we have tried to make the point that there are also community responsibilities. I mean, if in the schools we do not require physical education, K through 12, then it is unlikely that our children will be physically active and develop lifetime habits of physical activity.

If the school lunches include more fats and sweets than fruits and vegetables, then the eating habits of children are likely to reflect that, and as you know, we are suffering an epidemic of obesity in this country, both childhood and adult.

So we have tried to point to the community responsibilities as well as the personal responsibilities. And finally, that system will change the way we approach mental health, from one of blame and stigmatization to one of caring and support.

The second priority of our office is the elimination of disparities in health among different racial and ethnic groups, and we have targeted six areas and I won't dwell on those at this meeting, but would be happy to discuss them in more detail at a later time.

But we are pursuing elimination of disparities in health in areas like infant mortality and diabetes and several types of cancers.

The last priority is, I think, quite relevant to your work here, as all of them are, but certainly the last one, and that is to take a more global approach to public health, acknowledging that we actually live in a global community, that our food supply is a global supply. 40 percent of our fruits come from out of the country, 10 percent of our vegetables, 60 percent of our seafood. It is a global food supply when you go to the market.

But as we deal with infectious diseases, whether we are dealing with antimicrobial resistance, or agents in our blood supply, we are dealing with a global market, and therefore, the need to have a global system of surveillance and response to emerging infectious diseases.

I think that's the only way we're going to be able to assure that we better protect our blood supply in the future. We've got to have global partnerships and we've got to have early detection and response to new infectious diseases.

I just wanted to share that with you because your work here, in a lot of ways, is important to all of our priorities, but, certainly, the issue of a global approach to public health is directly related to the safety of our blood supply and the availability of blood.

So, again, thank you for your efforts and we look forward to a very exciting meeting here, today and tomorrow, and look forward to being able to review the results of your deliberations. Thank you.

DR. CAPLAN: Thank you, Dr. Satcher.

I wanted to just say that it really is exciting to see some of the work of the committee moving into practice with the look-back and the physical education and public education, and I think the committee is very grateful for the efforts of the Department and the agencies to move these recommendations along, and I'm very appreciative, too, of the importance and the emphasis, direction you're giving us to attend to prevention and I really do hope over the next two days that we can be thinking hard about what we could do, not only to have a safe blood supply but an adequate blood supply and that's really the challenge that faces us and all of the health care system and the nation as well.

So I thank you for those remarks.

What I would like to do now, since I'm sure Dr. Satcher has other places to distribute his prescriptions, is to move us very quickly into our first session and an overview of the safety of the blood system at this point.

We have two speakers who are going to talk to us about that, Harvey Klein of the NIH, and then I guess Jim Reilly and Dennis Jackman will split from the Blood Resources Association and the IPPIA.

So if I could get Harvey to come forward. Is he out there?

DR. NIGHTINGALE: Harvey is there. Harvey's slide projector is--

DR. CAPLAN: Oh, he's not here. He's coming.

DR. NIGHTINGALE: The carousel is on its way and we apologize for that delay.

[Laughter.]

DR. CAPLAN: While we're waiting for technology to catch up with intent, I see that I've lassoed Dr. Satcher for one more minute, and if he's here and doesn't mind, if anybody had any questions they wanted to direct to him, that would be fine, if that's all right with you.

DR. SATCHER: Questions or comments? They're very important to me, so--about any issues that we're working with.

DR. PILIAVIN: Dr. Satcher, in the beginning of your remarks, you emphasized the importance of essentially doing everything we possibly can to insure the safety of the blood supply, and including all of the most recent developments, which I assume you mean the B-24, and things like that.

When you were talking about your priorities for public health, one of the things you were emphasizing was the importance of equal access to care and public health issues, and after reading AuBuchon's article on the plane yesterday, I worried even more than I've worried in the past, about the amount of money that it costs to add one year of high quality life through putting money into making the blood supply safer, and I was thinking of all those kids in the poor parts of the United States who don't have their basic shots, and thinking in terms of the best use of the money that we've got. I wonder if you have anything to say about that.

DR. SATCHER: It is amazing, that you would ask that question. [Laughter.]

I appreciate it. I appreciate the fact that you're thinking that way, because I think those are the kinds of tough decisions that we are facing.

I think what we believe is that our health care system is actually big enough, in terms of finance, but that we have some major problems in the way that we are distributing those funds, and you don't solve those problems--even if we made a commitment today, the problem is we haven't a commitment for a balanced community health system.

But if we made it today, it would probably take 10 years to get to the point where it would really be paying off in terms of the funding aspect. It would pay off almost immediately in terms of preventing pain and suffering, but the adjustments would take years in terms of how it would impact the funding.

So the strategy of a balanced community health system is, in great part, one that considers what will it take to reach a point of cost containment in the system, so that we can redistribute the funds and allow universal access.

We spend enough money to provide access for every person in this country, to quality health care; but we spend enough, and so that we believe that the real issue is how do we change the amount that we focus on prevention.

Think about all of the money that we're spending on treating end-stage renal disease in people with diabetes, who could have had their diabetes controlled to the extent of preventing the end-stage renal disease, or one-third of them could have had it prevented, if it's Type 2 diabetes, by programs of physical activity and nutrition.

So that is the way we're thinking. I must confess that, therefore, I haven't gotten to the point of saying, now what implications do we have for the blood supply? and how much we invest in safety. But I understand your point completely.

I believe we can afford that, if we move toward a balanced community health system.

DR. CAPLAN: Keith.

DR. HOOTS: Dr. Satcher, as your second large goal you were talking about elimination of disparities, and particularly certain racial and ethnic disparities that exist in the United States, and even though our purview here is primarily blood, blood and tissue are closely related, and one of the problems that comes up is, as you well know, is the problem of unavailability of donor organs for minorities because of the genotype variations.

Is there a concerted strategy to address this issue, nationwide, to try to extend the number of people who are typed, particularly among minority groups?

DR. SATCHER: Yes. In our Department, again, that's an area of major focus. Ken Moritsugu, who's the Deputy Surgeon General, is leading that effort. I met with him and the national organization of blood donors two weeks ago because they're going to be playing a major role also in that strategy. As you probably know, 35 percent of--and I'm just talking now about organs--but organs and tissue, 35 percent of those are needed by minorities, and African Americans especially, because of hypertension and diabetes, and therefore, renal disease.

So we need a major effort and we are going to see a major effort in the country in that regard. But in our department, Ken Moritsugu, whom some of you know, is himself a donor, father, and husband, and is leading us in that direction. People like Clive Callendar, at Howard, who's also been out front, is going to be working very closely with us. It's a very important point. A lot of education, a lot of attitudes that people have about who needs to donate organs and tissue, a lot of cultural differences that we realize we have to deal with in the process, and we're talking about all of them.

MR. WALSH: Dr. Satcher, we appreciate your interest in the critical shortages of plasma derivatives over the past year, and we wish to certainly emphasize that that shortage still exists, and it prevents access to appropriate treatment to slow the progression of various disorders down with a lack of IGIV, and Alpha 1 protease inhibitor products.

We're also facing a circumstance, now, where HCFA is looking at restricting the reimbursement in their proposed regs to infusion therapies for chronic illnesses, and we would like to ask, that we need help with this issue in moving forward over the next, probably our next meeting.

DR. SATCHER: Okay. We will follow up on that.

DR. HERBERT: May I ask Dr. Satcher a question. I'm one of the speakers tomorrow, Dr. Victor Herbert.

Dr. Satcher, we've been trying to get the FDA to adopt our petition, that all fortified food which is fortified with folic acid, under federal law, be also fortified with B12, and when we were on the original panel--I say "we"--I mean myself and Ken Johnson of California--were on the original panel, it made the recommendation, and our recommendation was a fortification of B with both folate and B12. It came out with just folate. We filed a petition to include B12, for two reasons.

One, if you don't include B12 you harm thousands of fertile black females. Black females do not have the gene defect that nonblack females have, which gives neural tube defect babies to 2,000 nonblack females in the United States. Black females do not have that gene defect. Black females have a different gene defect, one which gives them pernicious anemia in their fertile years, whereas all the rest of us get pernicious anemia sometime between 50 and 90.

Secondly, it's harming not only those black females who are going on to irreversible nerve damage, and Ken Johnson has published a number of cases out of his clinic at USC.

But also millions of elderly are getting progressive, irreversible nerve damage because the folic acid in their grains is preventing the blood damage which tells all doctors the patients have B12 deficiency. So I plead with you to get them to act.

DR. CAPLAN: I guess we have a plasma question and a vitamins question.

DR. HERBERT: Well, since he asked for nutrition questions, I thought I'd give him one. Food and Drug Administration understand the issue and I don't know where the FDA is on it, but I think you make a very important point. Of course we've had this very powerful advocate down at CDC for folate fortification, Godfrey Oakley, and he's done such a great job, and I think you're right--we do need to move toward--

DR. HERBERT: But Oakley and I had a debate in the American Journal of Clinical Nutrition, which ended when he wrote, "Herbert is right. We should add B12 also." [Laughter.]

Those are his words in the American Journal of Clinical Nutrition, last year.

DR. SATCHER: Thank you very much.

DR. CAPLAN: Thank you for giving us the time.

Harvey?

DR. KLEIN: I put on this lavaliere. I hope that you can hear me and this is being recorded.

I want to thank you for inviting me to speak today. I am from the National Institutes of Health but I'm going to be speaking today as a clinical hematologist who is still responsible for transfusing patients with chronic illnesses, as well as an individual who's been responsible for collecting and processing blood for transfusion as a steward of the blood supply for the last 25 years.

I don't have any startling new information about blood safety but I thought what I'd try to do in the next 30 minutes or so is to frame blood safety in a slightly different way as it relates to availability.

I probably have no need to tell most of you that we have a national blood policy. We've had a national blood policy since 1974. It's long, it has many details, but the four principles which we have today are just as relevant as they were when this was promulgated in 1974, and that is the adequacy of the blood supply, the highest safety standards, as the first two principles. Universal accessibility, which of course can only be if we have adequate blood, and cost-effectiveness.

Now that's a fourth, and I think, frankly, that's very appropriate.

There's always a balance between safety and availability, and we've known that for many years.

During the AIDS epidemic, in the early years, we certainly knew how to provide safer blood based on the demographics of high-risk individuals, and in fact we knew that if we drew blood from the celibate, older, Midwestern farmer's daughter of northern European extraction, we'd have a very safe blood supply, but she was very unlikely to provide the 11- or 12 million units of red cells we need in the United States each year.

So, again, knowing that we could in fact make blood somewhat safer based on demographics and balanced by the need to supply adequate blood for the nation's needy. Certainly, the unavailability of blood is a safety issue as well.

We also knew in those days, that there were some 30 surrogate screening tests that had been proposed to screen blood, and we knew that some of them would probably be effective.

Many of you remember Alpha Thimasin [?], staff agglutination, quantitative IGG. If we had applied all of these to the blood supply back then, we may have had safer units but certainly not enough to supply the country.

Now most of us are concerned I guess about transmission of infection in blood but in fact there are many other areas of blood safety.

I'm going to concentrate on two today and I will spend most of my time on the transmissibility of infectious diseases.

I do want to start, however, by saying that the blood supply is remarkably safe today, and one of the ways in which it's been made safer is in a way that hasn't affected availability, and that's by applying the systems, and very careful and meticulous labeling to our collection, processing, and distribution of blood to prevent fatal, acute hemolytic transfusion reactions.

Most of you don't remember that this was the major cause of death from blood transfusion at the turn of the last century, and in fact if we go back to the 1940's, the paper by Michael DeBakey showed that the rate of fatal hemolytic transfusion reactions per red cell unit transfused was about one in a thousand, and just to demonstrate that this was not a fluke, a second paper, a year later had approximately the same rate of fatality.

Today, we can say that the fatality rate from acute hemolytic transfusion reactions is less than one in a half a million units transfused, and, again, that's a great advance based on efficiencies and labeling, and systems analysis.

Still, however, if we look at data from Jean Linden, published in 1992, a report of 104 transfusion errors, between the years 1990 and 1991, I hope you won't be astonished to find, as I was, that one in 19,000 units transfused was transfused erroneously, and that in fact if one corrected for under-reporting, one in 12,000 units transfused is given to the wrong patient.

So there are a number of things that we can do to improve blood safety, that don't impact on availability.

But let's move on to infectious disease because I think that's where the nation is primarily concerned.

What are the conditions for transfusion-transmitted infection? First of all, there should be an asymptomatic viremic phase in the blood donor. We screen blood donors by history and physical examination, and so they should be asymptomatic to pass our screening, and yet they must be circulating the agent in their blood to be dangerous.

The virus viability must be maintained during the storage of blood, and, again, we're fortunate. In some instances, for example, the spirochete in syphilis doesn't survive well at 4 degrees, and so that's an added layer of safety. But most viruses, unfortunately, survive entirely well, both at 4 degrees Centigrade and in the frozen state.

The recipient I have here must be seronegative and that's really not correct. The recipient must be susceptible to the agent, and, finally, we transmit lots of infectious agents by transfusion, but most of them don't cause disease, so the agent must be capable of causing disease.

Why do I give you these simple facts? Because all of them are important in, on the one hand, balancing safety of blood; on the other hand, providing availability of sufficient blood. I will try to demonstrate why that should be.

Hepatitis A is really not a problem for cellular blood components. It's a small non-envelope virus, but transfusion association is so rare that it's reportable. Now I'm not talking about units of fractionated, pooled components, but single units of blood. The reason is that there is no carrier state, and so you must be very unfortunate to catch a donor who's recently been infected with Hepatitis A, who's circulating virus but isn't, in fact, symptomatic.

So this really isn't much of an issue, and we don't screen blood for Hepatitis A, and I don't believe we should.

Hepatitis B of course is a different story. Testing has been available since 1968 and this is a real success story. We have sensitive and specific assays, but they're not perfect, and so Hepatitis B is a dramatic success story but it's still a problem, and the problem is here.

As most of you know, if we took an individual and infected them at .0, it would be several weeks before our screening tests for Hepatitis B surface antigen became positive.

This period of time is called the window. It's a window during which a donor is infectious but asymptomatic, could come, be screened, be tested, donate a unit of blood that's infectious, and not be detected.

These are estimates. They are calculated estimates of the infectious windows for a variety of agents that are transmitted by blood. You can see for HIV, the estimate is 16 days with a range of 6 to 38 days, and for the other agents the infectious window is substantially longer, suggesting that if we had better, more sensitive tests for these agents, that we could either close this window or eliminate it altogether, blood could be safer. The question of course is at what cost?

And by cost, I'm not talking dollars today, but availability.

Hepatitis C, as you've heard, is a major problem. 200,000 new infections, annually; but not from blood. Blood is a very small part of that. About 5 percent, or less, is related to blood transfusion.

Once again, there is a window. Signs and symptoms of infection with Hepatitis C are usually minimal, so you certainly can get infected donors, and as I showed on the previous slide, there is in fact a window period of time.

Now, it's not nearly as bad, perhaps, as the press would lead us to believe. 85 percent of those who are infected will develop persistent infection, but only 20 percent really develop severe disease.

Well, 20 percent of a large number still is a national problem, but it's not 85 percent of a large number.

Now this is an important slide, and many of you have seen this in various iterations over the years, but I thought I'd spend a few moments on it anyway.

These are data from the National Institutes of Health, which you can see, go back to the year 1964. They are prospective post-transfusion hepatitis studies where specimens from the donor were tested or saved for future testing, and the recipients of blood were followed, over time.

If you came into the Clinical Center Hospital at the National Institutes of Health in the 1960's for a valve replacement, your chances of getting transfusion-associated hepatitis were about one in three. About 33 percent. In 1972, three actions were taken, and all of these are important.

Hepatitis B surface antigen testing was introduced, an all-volunteer blood supply was begun at the National Institutes of Health and the number of units per open-heart surgery case was reduced.

Those three, together, resulted in a dramatic drop in hepatitis transmission in prospective studies.

Now many people have said, well, that's because you introduced Hepatitis B screening, but as you can see, although Hepatitis B dropped, the dramatic drop really was in non-B hepatitis, what turned out to be non-A, non-B hepatitis, so it was the all-volunteer blood supply and the reduced number of exposures that were just as important, if not more important, than a specific test for hepatitis.

As we go through the 1970's and 1980's, a variety of other measures were introduced, including more sensitive screening tests for Hepatitis B, surrogate tests, removal of high-risk populations, and all of these dropped the risk of hepatitis at the National Institutes of Health.

With the advent of Hepatitis C testing in 1990, you can see, hepatitis was virtually eliminated in prospective studies, and in fact the risk of transmission of hepatitis today is so low, that one can no longer really do prospective transfusion studies. One must do calculations, and that, again, is a real success story, although the rate is not zero.

Now the public is thinking a little bit today about Hepatitis C, but, by and large, the public is still mostly concerned with AIDS and with HIV.

As you know, HIV is carried about by one in 300 Americans, far fewer blood donors. If you receive a unit that's infected with HIV, there's a 90 percent chance that you will be infected as well.

As I'll show you, we have introduced screening questions for high risk, and all blood is tested by sensitive and specific assays, and now I think this figure may be a little out of date, but fewer than 50 infections have been reported since 1985.

We can calculate the potential number of infections, but, really, once again, we can't do prospective studies because the rate is so low. A real success story.

Now, these are data that were published by Dr. Busch. They're model data. They're based on the transfusion safety study, and specimens in San Francisco, and what they show are a few very important points.

Again, these are years on the X axis, and this is the risk of HIV per unit on the Y axis, and as you can see, in 1981, when the first AIDS cases were reported, before they were known as AIDS, before we knew there was an epidemic, before we had any idea what it was, the risk in San Francisco was very high.

By June of 1982, when the first hemophilia-associated cases were reported, the risk was even higher. When the first pediatric case of transfusion-associated AIDS was reported in the end of 1982, the risk was around 1 percent. Phenomenal. No one had any idea about this, and it was at about this point in time that the blood collecting agencies instituted screening questions to eliminate high-risk donors from the donating population, and there was a massive national campaign of education about AIDS, and, again, one can see the dramatic drop--and this is very important. This is long before HIV was discovered, and it was certainly long before an HIV screening test was implemented in 1985.

So by appropriate public health measures, the risk dropped from almost 1 percent to a very low number, and of course with the advent of sensitive-specific screening tests, HIV has almost been eliminated from the blood supply.

Once again there is a serologic window. Using HIV antibody, you can see that there's a substantial window. When HIV antigen was introduced, it narrowed the window a bit, and when we go to RNA testing, the window will be down to about 11 days, and in fact data from chimpanzees suggest that individuals who are donating in this period of time may not really be infectious at all.

So we have the opportunity to totally eliminate HIV infection from blood transfusion.

So if this is such a remarkable success story, then what's the problem? The problem of course is emerging infections. We talked about HIV 1 and 2, but there are a whole host of retroviruses that may come from abroad, or may evolve through other means. There are a variety of parasites that are transmitted by blood.

On a worldwide basis, malaria is by far and away the most important transfusion-transmitted disease. In the United States we see Babesia and in the Southwestern United States and in Central and South America, and Mexico, Chagas disease.

We'll talk a bit about prions. There are new viruses. There are tick-borne illnesses, and of course there are bacteria. So we're certainly not out of the woods.

My apologies to Gary Larson, if you can't read this. This is how viruses get around, and this is a man at a bar saying, "You're from France? Wow. You have lovely eyes." And his viruses say, "Hey, everyone, we're going to Paris."

As Dr. Satcher said, and as Marshall McLuhan said, we live in a global village, and anything that's in Africa, Southeast Asia, or anywhere else in the world, today, can certainly be in the United States tomorrow.

This was the report of a Group O strain of AIDS virus that was reported for which our screening tests were not effective.

That simply indicates that there are other strains, there are other mutants that we can expect will appear, that our screening tests will not detect. Will they cause epidemics? Probably not, but we need to be worried about that. We can't have a zero-risk blood supply.

Most people don't know that there's malaria transmitted by blood in the United States. There have been 103 cases reported between 1958 and 1998, so the rate is about one case in every 4 million units transfused, and in fact the parasites can persist in an individual who's had malaria, asymptomatic, for up to 40 years.

We don't have any licensed screening tests and there aren't any good ones anyway. So screening by history remains the mainstay for malaria and in fact if we screen adequately, we can predict that we would eliminate 97 to 99 percent of all malaria that would threaten to come into the U.S. blood supply.

That assumes that history is given accurately, and I know Dr. Williams will be talking a little bit more about that later.

We have bacteria in the U.S. blood supply. These data from the American Red Cross, .2 percent in our culture-positive red cells, zero to 10 percent in platelets which are stored at room temperature, and these are the data from the Bavarian Red Cross. Why is that important?

Well, again, it's been reported that certain bacteria are particularly dangerous when they're transmitted from blood to a sensitive patient. Yersinia is one of those. Prior to 1987, there had only been six cases reported in the United States, but nine cases have been associated with red cell transfusions reported since then.

All of the recipients became quite symptomatic. All of the donors, all of the donors were well at the time of donation.

Five of the nine donors had a history of gastroenteritis within four weeks of donation, and all of the transmission from infected red cell units were from units that had been stored more than 25 days.

Why is that important? Well, we don't have any reasonable screening tests for Yersinia or for other bacteria at this point in time.

Some suggested that maybe we ought to screen by history. We could have eliminated half of those donors if we'd screened for gastroenteritis by history. But think back, in the last month, and how many of you may have had a gastrointestinal upset. So the denominator here would be enormous, and if you're thinking about availability of blood, you can't ask blood donors whether they've had an upset stomach in the past four weeks, and then eliminate them if they had.

Others suggested shortening blood storage since the older units of blood were the units that transmitted, but for the nine or so cases that had been reported in five or six years, you'd eliminate 10 percent of all red cell units, and, clearly, that's really not an acceptable tradeoff.

Other screening tests have been suggested. This is Hepatitis G, and these are data from Harvey Alter at the National Institutes of Health. Hepatitis G was reported as a new hepatitis agent. In this particular patient, both the patient was negative at the time he went to surgery. He received a unit of blood and developed hepatitis.

The unit was subsequently found to contain this so-called Hepatitis G virus, and as you can see, the patient turned positive for Hepatitis G virus by PCR, remained positive for four years, until he died of other causes.

When these kinds of data began to appear, people said, "Screen all blood for Hepatitis G." We can do that. As it turns out, Hepatitis G virus is readily transmitted by blood.

It is frequent in the donor population, but it doesn't cause hepatitis. It doesn't even exacerbate preexisting hepatitis. To the best of my knowledge, it's not pathogenic. So there's no reason to screen blood for Hepatitis G, and as we get better molecular techniques, we are going to find more of these agents. This is a second one. TT virus, a virus discovered in Japan, a non-envelope virus.

It's not really a parvovirus; belongs to another class. In our NIH specimens, it was present in 7.5 percent of 400 consecutive blood donors. So it's frequent in the donor population. It was present in 9 percent of the patients that we screened at NIH, and it is readily transmitted from donor to recipient.

However, it's not associated with hepatitis and it does not seem to exacerbate other kinds of hepatitis, and as we find more and more of these viruses that are readily transmitted by blood, we have to be cautious not to try to introduce tests to screen them out. Many of them will not cause any harm.

This is a report of tick-borne pathogens. National Guard troops at Fort Chafee, in Arkansas, after a bivouac, many of them were found to have been bitten by ticks. Several of them became ill, and so all of their units of blood were recalled.

I think we have to be aware that those kinds of things are going to occur, and we will again have to balance availability versus safety, or potential infectious risk.

I was told today that we weren't really going to concentrate on issues of spongiform encephalopathies, but this is clearly a very important issue, extremely important regarding availability, and I'd be remiss if I didn't touch upon it somehow.

Creutzfeldt-Jakob disease. Who knew about that before three or four years ago? Only the neurologists. It's a dementing illness. It has a familial and a sporadic pattern of occurrence.

It's clearly been transmitted by brain tissue, by dura mater, and by a single corneal transplant. In the 1980s and early 1990s, about 3,000 patients were infected with the agent that causes Creutzfeldt-Jakob disease when they were given injections of human growth hormone which was made from pituitaries from patients who had been infected. These were autopsy pituitaries.

But neither animal studies nor epidemiologic patterns suggest, in any way, that the agent associated with this disease is transmitted by blood. So animal studies are, at best, inconclusive. Now, because we can't prove it doesn't mean it doesn't exist. You can't really prove a negative.

Looking at transfusions in 202 CJD patients show that they don't differ from controls in terms of transfusion. There hasn't been any Creutzfeldt-Jakob disease in patients with hereditary coagulopathies, or with hemoglobinopathies in chronic transfusion.

And look-back studies, including a recent one by the Veterans Administration, has not been able, in any way, to associate Creutzfeldt-Jakob disease with blood transfusion.

Nevertheless, we have instituted screening questions on the chance that an agent associated with CJD may be transmitted by blood. We ask all donors about a history of Creutzfeldt-Jakob disease and if they have one blood relative, we defer them, and we discard their unit.

If they have two or more relatives, we define these individuals as at-risk family, and we quarantine their intake products and we offer them testing. And if they test positive, or if they refuse testing, we notify and counsel patients who receive their units of blood.

I don't quite know what we counsel them about, but we do counsel them.

Now this isn't a big issue for CJD. It's a rare disease, and I suspect with our screening questions we don't eliminate very many people, and don't impact much on availability of blood in the United States. But of course that's sort of just the start.

There's another entity, bovine spongiform encephalopathy, "mad cow disease." It's a fatal disease in cattle. It was identified in England in 1986.

It has an infectious agent, we think, similar to the scrapie agent, and it appeared associated with feeding cattle with sheep offal.

And a former, new variant of Creutzfeldt-Jakob disease appeared in humans, in Britain, and was associated with eating British beef.

This variant Creutzfeldt-Jakob disease was first described in Britain in 1996. It was associated, linked to "mad cow disease." There were 39 deaths through March of this year.

It is an interesting disease, in that while CDJ is in older patients, this disease is primarily in younger individuals, for reasons we don't quite understand, and somewhat disturbingly, in the last quarter of 1998, there have been nine deaths.

Now there is no association with blood, and I suppose this is the curve of the cumulative mortality in the United Kingdom from this new variant Creutzfeldt-Jakob disease. If we didn't see this jump in the last quarter of 1998, we might not be quite as concerned.

So we are concerned that perhaps the United Kingdom may be in the early stages of an epidemic, but, once again, there's no evidence that this is transmitted by blood.

So there are a variety of unanswered questions.

Did transfusions submit either CJD agent? Or a new variant CJD? We don't know. If so, is it a prion? What is the agent? If it is transmitted, what are the circumstances under which it's transmitted? Do all components transmit? Does the dose matter? Does the duration of number of transfusions, over time, matter?

And, finally, is there a rational public health intervention? And I think that's the important one.

People have suggested that Americans who have visited Britain be deferred for some period of time, perhaps if they've eaten beef in Britain, maybe at Wimpie's at Heathrow Airport.

But again I stress: rational public health intervention for an illness that has never been demonstrated to be transmitted by blood, and for which there is no evidence that it should be.

Well, how do we reduce the risk of infection further, without impacting on the availability of blood.

Judicious use of blood, using it when it's indicated. That's like "mother and apple pie." Improved screening. You'll hear much more about screening questions later on, and that's an important one.

We are already moving on improved testing, as you know, with genome amplification testing, PCR, and things like that, that close the windows. Getting more repeat donations. Microbial inactivation is very important for plasma fractions. Perhaps it'll be important in the future for cellular blood components, and alternatives and substitutes, which you'll hear more about tomorrow.

I do want to point out, in closing, a few important things for cellular blood components. We have an all-volunteer cellular blood component blood supply.

Back in 1972, it appeared to be very important in improving safety. We think it's still important today. These are data from California, by quarter, of donors who confirmed HIV positive by screening and by Western blot.

These are the rates in volunteer donors. These are the rates in paid donors at plasma centers. Virtually every agent that has been discovered and for which a new screening test has been found has a higher prevalence in paid donors than in volunteers.

So I say to you that we have a safe blood supply based on volunteer donors. Before we change how volunteerism is defined, or what we allow to be done to recruit donors into the supply, we should demonstrate that any action taken is no less safe than what we have now.

The burden of proof is not on the collectors to demonstrate that donors are as safe. The burden of proof is in the other direction.

Validity of screening history is very important, and, again, we know that screening histories have inaccurate data. Dr. Williams is going to talk more about that.

We have screening tests to narrow the window, to detect viral variants for seronegative individuals to eliminate current testing errors, and of course the big problem is to try to screen for emerging agents.

Finally, I thought I would close with a few figures on what the risk is today and it's very low.

As you can see, fatal hemolytic transfusion reactions is somewhere in the range of one in 600,000, one per 600,000 units transfused.

HIV infection, somewhere between one infection in 500,000 to a million units transfused.

Hepatitis B. This figure is probably high. It's probably lower than this, but certainly no greater than one infection in 66,000 units.

Hepatitis C. One infection in a 100,000 units.

This is a very, very safe blood supply.

So I would like to summarize by saying we collect and transfuse a lot of blood, and blood components in the United States, about 16 million cellular components, 11- to 12 million units of red cells, 4 million units of platelets, as well as a few million units of fresh frozen plasma.

The advances in screening and in testing, in processing, have improved our safety, dramatically.

Zero risk, as with anything in medicine, is certainly and admirable goal, but it's somewhat unrealistic. Our task I think is to make sure that well-meaning interventions don't compromise either blood safety or blood availability.

Thank you very much.

DR. CAPLAN: Why don't you stay there just for a couple of minutes to take a couple of questions of the panel wants to direct some questions, Dr. Klein?

DR. GUERRA: Dr. Klein, thank you very much for a very informative presentation. I have a couple of questions.

You didn't mention nor have we in this group discussed perhaps other sources of contamination, for example, with heavy metals and/or in the instance of some of the biochemical toxic substances, say because of long-term exposure to insecticides, or cholinesterase perhaps might accumulate. Are those potential risks?

Then the other question I had for you, you shared with us sort of the overall cumulative data, but if you were to disaggregate by region, would there be any significant differences?

DR. KLEIN: Taking the last question first, yes, there are. There are clearly differences in different regions of the country, and, again, I believe some of this is going to be covered later on when some of the demographics are discussed, large cities versus rural areas, the Midwest in general is safer for those of you who are transfused, but maybe not in Chicago. So, yes, the risks certainly are different as you look in different areas of the country and different demographic groups and in different cities.

The first question is an interesting one. Those of you who follow your medicine in the Washington Post saw recently that plasticizers were back in the news and plasticizers potentially being very toxic, and certainly there are lots of things in blood besides infectious agents that are potentially toxic.

We have had some 40 years of experience with heavy transfusion, perhaps more than that, chronic transfusion, not the patient that gets a unit or two to save his or her life but chronically transfused individuals. And, by and large, most of these have not come out as being major problems, and certainly in the risk/benefit ratio have not raised the risk over what the benefit might be, including plasticizers.

So, to answer your question as best I can, I don't really know what the cumulative risk of pesticides in transfused blood is, or of plasticizers, for that matter. But I do know that you get plasticizers from your TV dinner, and probably the risk of these are not sufficiently greater than the risk that we have from exposures in our general environment.

DR. CAPLAN: Dr. Gilcher?

DR. GILCHER: A comment, Harvey, that I've thought about for a long time, and that is the rate of hepatitis B should theoretically go down as the recommendation--in fact, requirement for vaccination is occurring almost universally in this country. Can you comment?

DR. KLEIN: Yes, I had that actually as a last line on that slide, and I should have used this, as Dr. Satcher did, to say that yes, everyone should be vaccinated against hepatitis B. All children are now. Health care workers have had that advice for a long period of time. The vaccine is clearly safe and effective in 90 to 95 percent of people who receive it, and, yes, that should eliminate much of the hepatitis B that's transmitted by transfusion and by other means as well.

DR. GILCHER: I'm going to come back with another comment. I was waiting for that one. I've done two studies in my tour in transfusion medicine on hepatitis A in donors, one in Pittsburgh and one in Oklahoma. And what I have found is, looking for anti-HIV before the advent of the vaccine, that between 25 and 30 percent of the donors in both of those areas where I've been, in fact, have had hepatitis A and didn't know it. These were individuals who said "I did not have hepatitis" on their screening.

Again, you pointed out very clearly that hepatitis A has no carrier state. I want to point out that it's a very common disease, no carrier state, and, in fact, we are currently excluding individuals who have had a clinical history of hepatitis A when there are literally hundreds of thousands, if not more, people who have had subclinical and, in fact, say "I have not had hepatitis" and, therefore, are acceptable as donors. We could, in fact, I believe, include these people back into the donor base once they are cleared of having acute disease.

How do you feel about that?

DR. KLEIN: Well, again, I think it's a risk/benefit issue, Ron, and the hepatitis screening question has never really been validated, as you know. We don't know how effective it is. We think it's an effective screening question, and I guess the issue is whether you want to modify that in some way, knowing that there are still agents that cause hepatitis that may be carried for long periods of time that could be a risk and that patients may have had a case of hepatitis, as well as hepatitis A, as well as hepatitis B. And you might be able to clear them by your current screening tests, and they might still possibly be infectious.

DR. CAPLAN: Jay?

DR. EPSTEIN: Ron, if I could just comment, you know, FDA has an initiative to update the regulations. The history of hepatitis regulation goes way back, I think like to 1958. And we will be having a scientific workshop on the question of history of hepatitis later this year.

DR. ALLEN: Doctor, just one quick question. On your slides, you said the average age of the people that die from new variant was 29 years old. Is that correct?

DR. KLEIN: Almost all of them have been 29 or under, yes.

DR. ALLEN: And isn't that also the age of the Utah donor?

DR. KLEIN: It could be. I don't know what the age of the Utah donor was.

There is one patient who was 43 or 44, but I think it's very peculiar and as yet not understood why younger individuals happen to have this disease.

DR. CHAMBERLAND: I just wanted to comment that there has been a thorough investigation of the Utah donor, including epidemiologic and laboratory information, which indicates that that donor did have classical CJD and not new variant.

The information that--the diagnosis of classical CJD was made by examination of material from a brain biopsy, and the application of various immunohistochemical and Western blot-type testing. So I think we feel very confident that we did not in Utah see a case of new variant.

DR. BUSCH: Harvey, you presented a little bit of data on hepatitis G and TTV, and you sort of said that, you know, we could have tested. In truth, I think those viruses are prevalent--the viremic state is prevalent at 2 and 6 or 7 percent respectively. But there is no antibody assay that could have been implemented, and at that point in time, several years ago, we didn't have a nucleic acid technology in place.

So, in a sense, I view us as fortunate. I think if we had faced the hepatitis G data as it was evolving over the first several years, showing clear high prevalence in donors, very high rates of transmission, debate over association with hepatitis, if we had had a nucleic acid platform in place, many of us--and I remember the votes over time as Harvey Alter would present it and ask who would you test, and in the early days most people said yes, that if they had a test, they would. But in a sense, fortunately, with hindsight, we didn't.

And I think if we're going to face these decisions down the road, I think one of the suggestions I think Jay Epstein had at a prior meeting was this committee really needs to tackle the paradigm of decisonmaking in infectious disease screening. And I think a lot of the repositories that Harvey and others have built have allowed us to now fairly quickly address the transmission rates, the prevalence rates. But the long-term disease outcome questions are much more difficult to tackle. And expecting new agents down the road, I think we are going to just face this decision where we will have the potential to test. We're kind of seeing these reactions to history questions related to CJD British donors. In the absence of clear evidence of non-risk, decisions are being made to do things that down the road I think will be proven to not have been necessary.

Just any comments on that.

DR. KLEIN: Yes, I think that's one of the most important things this committee can do.

Now, I was on the side where I would not have screened for hepatitis G based on the data that we had at the National Institutes of Health, which suggested very early that it was not a hepatitis virus. And I think the lesson to be learned there is that as our molecular techniques become more sensitive, we're going to be pulling all kinds of viruses, and other agents as well, out of blood, and we have to balance the availability against the safety without any question.

And the paradigm that's used to make those decisions is absolutely going to be critical, and I would simply emphasize that moving too quickly with the thought that you must be making blood safer can be disastrous, if, in fact, it's going to limit the availability of blood that is so important to so many people in the United States.

I just returned from Vietnam, where I know you were last year, Mike, where they collect 6 percent of the needed blood in the country. They have about a 20 percent rate of hepatitis B, about a 12 percent rate of C, and about a 1 to 2 percent rate of HIV.

If you want to see problems related to lack of availability of blood for very common things and people die, just look at the emerging countries, and I think we need to be very careful that we don't get part of that problem in areas where we don't need to. We're dotting i's and crossing t's in terms of safety. We're on the edge in terms of availability.

DR. PENNER: Harvey, just a quick question. You didn't mention much about the non-infective agents and the possibility that the immunosuppressed individuals who receive those products might well be able to become infected. Could you add anything on that?

DR. KLEIN: The immunosuppressive effect of blood?

DR. PENNER: No, the immunosuppressed patients who receive blood products that supposedly have agents that are non-infective, in quotes.

DR. KLEIN: For example, cytomegalovirus in the bone marrow transplant population. Yes, I didn't go into that in any detail. There are some agents that we know are specifically toxic for certain categories of patients--immunosuppressed patients, neonates--and we do have screening criteria for those particular kinds of patients.

It's not a perfect paradigm, but it's a pretty good one.

DR. GOMPERTS: Dr. Klein, I'm trying to follow your train of thought. Are you suggesting that the introduction of the sensitive PCR technologies has the potential to impact the actual supply of blood products? In other words, as the technologies advance, the potentially infectious agents are identified, these technologies are used, that in actual fact under the current system that we have in the United States, that there could potentially be a substantial availability issue?

DR. KLEIN: I don't want to be misunderstood because I feel very strongly that introducing PCR-type technology for the agents that we know are infectious is going to be a boon to the safety of the U.S. blood supply for things like hepatitis C, possibly even for B as new data come out, less so for HIV, as everybody knows.

But I think what I'd like to emphasize is that with this kind of technology we will discover all kinds of viruses that have been passed from donor to recipient since blood has been transfused and for which there is no evidence of disease transmission. The final line on my third slide was that there has to be a disease associated with the agent.

That's not to say that there isn't some disease that has a 40-year incubation period that we don't know about now. But my caveat is every agent, every new agent that we find in blood, we shouldn't necessarily think that we have to screen out of the donor supply. Yes, if we do that, we're going to have a serious availability problem as we find agents like TT and hepatitis G that are in 6 or 7 percent of the donor population.

DR. GOMPERTS: Thank you.

DR. CAPLAN: Maybe I'll take the last question here. Do you think we have the infrastructure set up to do the kind of monitoring, epidemiological and toxicological, to make an assessment of what we discover in terms of molecular viral variability?

DR. KLEIN: That may be better answered by someone from the CDC than from me, but, no, I don't think we have the ideal infrastructure available for looking at emerging issues in the safety of blood.

DR. CAPLAN: Okay. Thank you. On that happy note, we can--did you want to say something, Mary?

DR. CHAMBERLAND: I guess I just did want to respond that under the rubric of emerging infectious diseases, CDC in collaboration with state and local health departments and many other professional organizations has actually embarked on a whole cadre of various surveillance approaches to try and detect emerging pathogens, not restricted to the blood supply but as they enter the population. And I would be happy to discuss that with anybody who would like more information.

DR. KLEIN: And if I could give a little plug for that, I hope that will be heavily supported. It's a very, very important initiative. DR. CHAMBERLAND: We hope so, too.

DR. CAPLAN: All right. I'd like to have Mr. James Reilly and Dennis Jackman come forward. I guess Jim Reilly is up first from the ABRA.

MR. REILLY: Thank you. We're going to a little team effort here for the--everybody can hear me? I'll see what my leash allows me to do here.

Steve asked us if we would talk a little bit about plasma products. As I think most of you know, the system for the collection and manufacture and distribution of plasma products is a little bit different for whole blood than for transfusion, mostly in the area, first, as Harvey pointed out, that there are differences between paid and volunteer. The plasma supply is largely based on paid. And then we have trading war opportunities for interdiction of any kind of at-risk type of event.

So as a group, we are divided, though, into two parts of the manufacturing process, collection and then the further manufacturing process, which really is the reason that, if you will, it's a tag team effort between Dennis and I.

What I wanted to do, though, was to start out by showing you this chart, which is just hypothetical in nature, to give you an idea of what our goal and objective is in the manufacturing process.

On the left, the axis there is just intended to demonstrate relative risk, and on the right--or on the bottom is the manufacturing process. If you start over at the left, it's the donor all the way through ultimately to a patient at the other end. And what our goal here is to show you that you start with the population that would be what we would consider the most at-risk group that we have in that whole process, and our objective is to pull that safety curve down to the bottom line, to that low relative risk line, as early in the process as possible.

This shows a gentle curve. I think in reality it's a relatively steep curve from the population through to donor screening. And then it's pretty flat across the line at that point.

As I said, we have kind of divided the process up into two of us here, ABRA on the left there representing the collection interest, which is sort of a different specialty, if you will, or different competency, and then Dennis, who will deal with the IPPI and the fractionation, which is sort of the post-pooling, if you will. So we'll deal with it up to the point that we have taken all the plasma and put it into one single pool, and then Dennis will carry it forth from there.

What I was going to talk to you about is a program that the industry has developed called the Quality Plasma Program. These are a couple of basic facts and figures. One thing that is not on there that I think you probably should, if you don't already, appreciate is this program is industry standards which are above and beyond those of FDA or any of the other government agencies around the world that we have to deal with.

The products that we manufacture on the plasma side are distributed on a global basis, so we are subject to all of the FDA regulations, and we assume that's a baseline to this program, so I won't talk about them in any major detail. We also are subject, most of our collection centers, to regulations out of Germany, the UK, and many other governments around the world. So we're not dealing with a single agency. We're often dealing with multiple agencies.

This particular program that I'm going to talk to you about was established in 1991. It's a series of standards above and beyond those other regulations, as I described. About 380 of the 410 commercial FDA-licensed facilities here in the States participate. That's about 11 million liters of source plasma for further manufacture. The program has been endorsed by the National Hemophilia Foundation, not once but twice. When it was originally conceived, they passed a resolution supporting it, sent a letter to all the fractionaters, said what are you doing about complying with this, insisting that they did. And then more recently in October of 1998, they renewed that resolution--in fact, went into much more detail, saying that they are very happy with the progress, in fact, that the program has made.

Beyond that, it enjoys worldwide recognition. Most governments, when they put out tender offers for a product, they ask the question about it, Is it QPP certified for the source material? Virtually every fractionater around the world requires it as a part of their specification before they will entertain the purchase of that plasma.

The basic standards in the original program, I'm not going to go into any of these in great detail because we have somewhat limited time this morning. But basically they cover employee education and training issues, establishment of a community-based donor population--this is by asking questions, for instance, demanding that they have permanent fixed addresses so that when we find a positive, we can contact them and counsel them as appropriate--if they live within a fairly narrow geographic range of the facility, and a variety of other screening questions.

Facility criteria are fairly straightforward, both interior and exterior facility criteria to try to make sure that it operates in a medical capacity, that it's clean, neat, well organized, adequate space, et cetera. Donor screening, we insist that not only are FDA rules adhered to, but that they try to go a little bit farther in the educational process, particularly in the high-risk area, and assess competency of the understanding of the questions that they are asked and whether they made an informed decision about self-deferral.

We operate a National Donor Deferral Registry. We have a computerized national registry which allows all of the facilities across the United States to share the deferral list for HIV, hepatitis B and C, and that any facility can call an 800 number, using appropriate security codes and passwords to maintain confidentiality, can check a donor against that registry to see if they've been deferred at another facility somewhere.

We established in 1991 what would now be considered a somewhat crude viral marker rate standard. At the time it was a somewhat novel idea. In light of today's knowledge, it would be viewed as crude, and I'll explain how we've updated that. And then we ensure that all of these standards are adhered to through biannual inspections by a third-party auditor, who then makes a recommendation to us about continuing certification, requirements for changes if they're not in complete compliance, or denial of certification.

We have upgraded the program a number of times. I'm going to break it into two categories, '91 through '97, and then '97 to the present. In this time period, '91 to '97, we upgraded the educational requirements. We upgraded the minimum training requirements for employees within collection facilities. We have upgraded the National Donor Deferral Registry several times with fundamental operating system improvements. It's been FDA 510(k) cleared as a device, and we're proud or concerned about now not only being a trade association, but also a registered device manufacturer.

We have added tests to it, P24 when it was introduced, and PCR as it's been introduced has been added to the list of things that can go on for permanent deferral. And I'll talk a little bit more about some more current updates to that.

The viral marker rate standard was updated several times. HCV was added in 1993 when we had sufficient data to establish a standard for it. Hepatitis B and HIV were lowered--not the standard was lowered but the numeric value they had to comply with was lowered, so the standard was, in fact, raised.

More recently, '97 to '99, more current, we have added a whole host of new things which we think have had a very dramatic improvement on the quality of the source material used for the manufacturer.

We added a qualified donor standard, a new viral marker rate standard, a quality assurance standard. We are in the process of upgrading the deferral registry. We're upgrading the inspection program, and I drew a line here to divide something here. We added an inventory hold standard and a PCR testing standard. Those two standards are not, in fact, a part of the Quality Plasma Program. They're managed by the fractionaters. I'll talk a little bit about them, but they're really covered within Dennis' group or managed by Dennis' group, the IPPIA membership.

The first one, the qualified donor standard, was introduced in July of 1997 officially. This is a very, very simple summary of it with three lines. The actual standard is about seven or eight pages long. But, fundamentally, what it requires is that no unit of plasma is acceptable for further manufacture unless the donor has gone through two donor screenings. So the donor comes in, they present themselves. We would quarantine that unit until the donor re-presented himself at some future point in time and passed the screening again. If he's been absent for six months or greater, we would treat him as a new donor again. So he would have to go through a requalify.

This chart is a little bit complicated, and I know that you can't read it. But let me just see if I can walk you through it.

Coming in on the left there is a new donor. Every donor that comes in, he's asked all the health history screening questions, both those that FDA requires, we require, or any other government agency would require of us. If that person is a new donor, the agency will go down on the left and start working their way across the chart in that bottom group.

So the new donor would come in. He would be subject to checks against the National Donor Deferral Registry. If he's on there, he's deferred. If he's not, he goes through to the next level. We would perform drug testing on him. If he passes that, he would go on to the next level without deferral, and he would receive a physical exam, a brief physical exam by a physician or an appropriately trained and authorized physician substitute, according to an FDA program.

If they get through that, then they would continue to move through the process, and they would give a unit of plasma. It would be tested for all the appropriate tests: hepatitis B, C, HIV, et cetera. The unit would be placed into quarantine, and it would be left there until the donor returned. If the donor returned, he starts this process over again. He gets to skip the initial ones. He doesn't have to go through the drug testing or the deferral registry check or the full physical examination. He goes through the standard donor screening health history questionnaire and the standard testing regime.

Only if he passes that would the units--that original unit and the second unit--then be releasable. They would be released, though, not for production. They would be released into an inventory hold system where we hold those units and any other subsequent units for a minimum of 60 days from date of collection. That allows us the ability to look back and retrieve those units if by chance subsequently they become positive or seroconvert.

This standard by itself, without the inventory held, has a marked improvement. What we have found when we looked at some of the data was that roughly 95 percent of all the positive donations that we found were in those first-time donors. So the mere act of requiring a second donation brought down our rate of positives, which is an indicator of the unknown, to some extent, that we put into the pool.

The next standard was the viral marker rate standard. This is a very new standard. As I said, the original standard we put in place was based on all donations not confirmed positive. We looked at hepatitis B, HIV, and hepatitis C, and said: What is your marker rate? What is the total number of positives over the total donations? We established an industry mean plus two standard deviations. We monitored it once every two years, and it was very effective at the time.

In light of the newer information and newer understanding of how the whole system worked, and with the qualified donor standard in place which now restricted our use of plasma for manufacture to second and third donation individuals, we established a new standard. It will take effect officially July of this year, although we've been looking at it and we'll have sort of a phase-in that started back in January.

Some of the added complications to it or complexities that we added to it were the new standard is based on center volume. What we found is that small centers were disadvantaged in the standard process because of just arbitrary findings of positive donors. If you had a small center that only had a few thousand or maybe 10,000 collections, one person could just blow them away. So we established a distribution if you will.

It's also based now on an ongoing assessment of performance, not simply biannual recertification. We collect the data ever month, and we analyze it in six-month increments all the time.

It is based on a reference rate. We established a rate for hepatitis B, C, and HIV, which then is plugged into a Basand (?) distribution table, which gave us a probability that they would be under or above a particular number.

The actual standard requires that they participate in the data center, so we have to get the data every month; that they maintain the viral marker rates for confirmed positive, qualified donors under the alert limits. And it's actually not just HIV, HCV, and HBSAG. There's actually a fourth one. We look at them in the aggregate as well. So they have to stay under each individual as well as an aggregate, which is slightly tighter than the three.

We suggest a sample to show you what a chart would look like. The reference rate on HIV is 1 per 100,000. The numbers for the reference rate are rounded. For hepatitis C it's 2 per 100,000. For hepatitis B, which amongst the qualified donors was our greatest risk, was 5 per 100,000, and the aggregate is obviously then 8.

This is an example of one of the Basand distribution tables that we developed from the reference rate center, and this could cover any specific time period. It is based on volume uniquely, up to roughly 11,000 donations. They're only allowed to have one positive, or they're over the alert limit. At the outer extreme, if they have 163,000, they're allowed five. That's to set an alert limit. That's not necessarily what we would expect them to be. In fact, most of the centers are well below that.

The way it's implemented is--this is really more of a time period slide here. Starting in January of this year through June, we'll have an introductory period where we will look at everyone's data, and when we get to the end of June, anyone who is above the alert limit for any one or more markers, we would send them a letter that says you are above the alert limits. If the standard was actually in place, here's what you would have to do to comply. Then starting in July through December, that letter will be a little bit less soft, if you will, and it will say: You are above the alert limit. You have exactly six months to get back in the alert limit, and we want to see your plan of action about how you're going to change your recruitment strategy, relocate the center, whatever you think is necessary to bring that number back down to something that we find acceptable.

Quality assurance standard will be introduced again in July of this year. Initially, it will be introduced as a self-audit. This second bullet point covers all of these areas in fairly substantial detail. It goes through a checklist. It says: What's in your SOPs? It looks at training of your employees, competency of implementation of that training, your participation in proficiency testing programs, validation, equipment maintenance, error accident and adverse reactions, records management, lot release, and quality assurance audits.

It also has as part of it definitions. One of the things that we found very important was the ability to use exactly the same language. So when we say quality assurance, everybody that participates in this knows what quality assurance means. When we say validation, we have a very clear understanding of what validation means.

Ultimately, it will be done as an independent audit by our third-party auditors, and I didn't put up the implementation date for that transition because what we would really, frankly, like to do is to expedite it. The current implementation date for moving it from self-audit to independent audit is, I believe, January of 2001. What we did when we passed the standard, the board agreed to the standard but said very specifically we would like to see that implementation date expedited, as early as January of 2000.

The last two that were on the list above the line, if you will, was the National Donor Deferral Registry upgrade. We are right in the middle of an RFP process to have the entire computer software and hardware platform that operates on redesign and updated using new technology, also making it implementable with the emerging computer systems of the plasma collection centers so that the checks can be done more frequently in real time, on a much more efficient basis.

Our inspection program, what we found is that as the program has grown, become more comprehensive, the qualifications of our inspectors and the whole way we have organized that with the training of them has to be completely re-evaluated. So they have been substantially upgraded, and we're going through a very intense process to bring the whole program up.

A couple of other non-QPP programs that I think are worthy of some note. The industry through ABRA maintains a number of training programs. We've been training collection facility managers in a variety of things, from regulatory compliance through to general management techniques for several years. We have also run and continue to run a number of programs to try and teach GMPs at the collection center. We have a program for teaching Clinical Laboratory Improvement Act procedures and techniques. We have a program for physician substitutes to try and improve their ability to interview and screen donors up front as well as counsel them subsequent to the discovery of a seroconversion, and a workshop on donor recruitment techniques.

Our laboratory directors, we are organized in a fashion that roughly 12 laboratories do all of the testing for about 13 to 14 million collection procedures a year for the plasma industry. Those 12 laboratories have developed of their own initiative a fairly comprehensive self-audit which tries to bring some uniformity to the way that they operate. They all participate in that activity very aggressively.

We have entertained a number of data question and study activities. Viral marker rates obviously set the standard. We are also looking at PCR testing and what those test results do and how they impact the safety of the material as well as our own standard. We performed a ten-year donation study several years ago now, which is also a duplication of the long-term donors, the same study.

Subsequent to that, we developed a donor dropout study. The ten-year study looked at people who had been in the program donating consistently for an entire period of ten years. What we did is we came back to that at FDA's encouragement, said: What about those donors who come in and donate very frequently for a short period of time, and then drop out and we never see them again? Was there some ill effect to them? So we have just completed that, and we expect it to be published, I believe, in the fall of this year.

We are beginning to entertain a donor demographic study which I think, again, will begin in the fall of this year and should be an ongoing event. And through all this, we can start to trend donations--frequency, demographics, viral marker rates, et cetera.

Now, a couple of pieces of data that demonstrate the value particularly of our newer initiatives. This chart is intended to show you what the viral marker rate, if you will, is that we are going to apply to the pool pre- and post-implementation of the qualified donor standard. So obviously all the positive units we removed. But if you use that as simply an indicator of risk, if you will, this is the way that we were able to demonstrate the value of the qualified donor standard.

The column on the immediate left is the unadjusted, if you will, marker rate for hepatitis B, C, and HIV there on the left. That date was EIA positive data, not confirmed positive data. So we had to adjust that to be a clear comparison, because our newer data was only on qualifieds from confirmed positives. So we tried to make an adjustment for that using published data on what the confirmatory rates did.

When we looked at HIV, that moved our confirmed positive rate--what we put in the pool, if you will, minus the positives, obviously--against what we put in the pool out of just the qualified donors. And that moved us from three-point--I can't read them from this far, so I'm hopefully working off a memory that's good. It was 3.8-something down to less than 1 percent. So a four-fold increase, or decrease, if you will. For hepatitis B, it was even greater. It was around 30, dropped down to 3. For HCV, it was 163 and dropped down to under 1. Very substantial improvement, we believe, through that standard alone.

The inventory hold period, the 60 days, which is largely implemented at the fractionater level, so this is where we overlap a little bit with IPPIA. But if you looked at that number, we went back and we pulled lookback reports for all the positive donors and said: How many of those units were we able to retrieve having the 60-day inventory hold period?

For HIV, where the window period is well under the 60 days, we were able to demonstrate that we retrieved 100 percent of all this that we identified as seroconverters. For hepatitis C, without PCR, the window period is up in the 80-plus day range, and we were able to retrieve about 54 percent. When we added in PCR, that window period dropped dramatically, and we were able to demonstrate retrieving 100 percent.

For hepatitis B, the rate we estimated at 59 days. I think Harvey said 56 in his slide. That's right on the edge of the 60-day hold, and we were able to demonstrate about 91 percent retrieval rate there.

Ultimately, we tried to make an estimate of the probability of a window unit entering the pool undetected, so this is a probability that it would not test positive, in other words, that the donor would be in the window and not return and so we were never able to demonstrate that they were in that window and that it might inadvertently end up in a pool. For HIV, with PCR it's down at 0.000049 percent; for hepatitis C, 0.000332 percent; for hepatitis B, 0.005. So we were able to demonstrate that the relative risk is very, very low.

Before I hand over the mike to Dennis, I did want to just sort of leave you with some thoughts about the program. As you saw, from '91 through to now, we have updated and changed it many times. These are some of the issues that we're dealing with. This slide has things on here that you may not be concerned about that were more internal for us. But donor screening is something that we believe in the short term we will take up and discuss whether there are improvements that we can make to the program there.

Documentation doesn't directly impact the safety issue but would substantially improve the operation of the industry by starting to uniform some of that.

Training and education is an ongoing evaluation. ISO 9000 is something we believe we will look at on a more long-term basis.

European and recovered plasma. We have made a decision that what we really want to do is have a baseline belief in what the quality of source material for fractionation is. So we are over the course of the next several years going to take the principles of this program, not necessarily the specifics of the standards but the principles involved in the program, and attempt to establish standards that would be applicable to non-U.S. collections that go into fractionation--obviously not for this country but for other countries around the world, because we operate globally--and also recovered plasma, both U.S. and European.

Applicant donor viral markers is something that we believe we need to take a look at, so that would be all those--retrospectively go back and look at all the donors that came in and never qualified for us, location guidance, improved third-party input, a little more actively talking to regulators around the world as well as patient groups and other stakeholder groups, and then constantly just looking at all the existing standards for upgrading.

A couple of things of note unrelated to QPP--well, one is related to QPP. I think we are interested in starting to look at having the program both grow this way but also get some more recognition and whether it wouldn't be useful to have it--I don't know that we would go to this level, but almost like the UL seal of approval somehow, that the logo would somehow be on the label or usable to identify this as having come from a facility that complies with standards above and beyond that of the government.

A second issue, which is not QPP, is that ABRA's Board of Directors recently decided that the weight of all of the regulations and the procedures that have been lumped on top on a fairly static, if you will, system for collecting plasma is starting to be overwhelming. And, you know, if you just take the basic--almost think of it as an assembly line, the assembly line to manufacture these products has remained pretty much the same over time, but we keep lumping on another procedure, another question, another test, and so on and so on down the line.

The weight of all those on the existing assembly line is starting to be a little overwhelming. So we are going to look at whether it's not feasible to have a complete re-engineering effort and look at how do we do this. Is there not a better way to organize the fashion in which we screen donors, collect them, distribute the product, et cetera?

I say that because I think to the extent that we are able to identify a better, more effective way, both from a point of efficiency as well as safety, that may well result in needs for adjustments in the way the regulations are written or into recognition of that differing position.

So, with that, what I would like to do is to go ahead and turn over the program to Dennis, who will talk to you a little bit about the fractionation end, where we put the finishing touches on.

MR. JACKMAN: Good morning. I'm Dennis Jackman. I'm vice president for North America for IPPIA. Our companies include Alpha Therapeutics, Baxter Health Care, Bayer, and Centeon. I just want to take a moment to acknowledge Jason Bablock (ph), our director of regulatory affairs, who had a lot of input into this presentation and to our programs as well.

I'm going to talk about safety issues that have been talked about, asked to do today. Jim, if we could just move to the next slide? And what I'm going to focus on is the current safety profile, but I'm also going to talk about another safety issue, and that's patient access, focusing on supply and reimbursement.

The next item there is, first of all, in terms of the current safety profile. In summary, I think this sums it up pretty well. In summary, there's been no transmission of HIV, HBV, or HCV since the introduction of screening tests and inactivation procedures in the United States when these procedures have been done properly. The statement of Dr. Tabor at a BPAC meeting, December of 1998. That doesn't mean we're complacent. It's a constant effort. It's ongoing, but it's a very positive statement, and I think the data support that.

How do we get here? Viral clearance is one of the key tools. Inactivation through treating, chemical treatment, removal, partitioning, filtration. The plasma fractionation process includes either one or more of these vital elimination steps. The bottom line is that each member has data that showed that viral clearance is excess of those levels that could be shown in the window period, and that's a very positive outcome as well.

We also go beyond the viral clearance and beyond some of the requirements, regulatory requirements. For instance, Jim described the source plasma issue, ABRA QPP standards. Our member companies only buy QPP certified plasma for production in the United States, so that's a very important safety check.

On the plasma derivatives, Jim talked about the 60-day inventory hold which our companies use. That's very effective. The NAT testing has been--Jim has talked about that to some extent. That's something that we are implementing across the board on those three viruses.

Donor exposure limitation, pool size, we have a self-imposed limitation of no more than 60,000 donors per end unit from our major product areas. And then we also have a patient notification system. If we ever need to do a withdrawal or a recall, we have implemented a rather unique program that can get to end users immediately to notify them of a recall or withdrawal. It's something the industry started voluntarily, funded. We have an advisory panel made up of major consumer groups that utilize these products and oversee this. So we think that's a very effective way to assure safety and assure confidence of the patients as well.

So I'd say on the status of traditional safety concerns we have an extremely favorable benefit-to-risk ratio. I think our benefit-to-risk ratio would really match up favorably with any product that's on the marketplace that's licensed as a human therapeutic.

Yet, we have plasma derivatives that are consistently in short supply. We have evolving regulatory requirements, GMPs not static, we have to--we're trying to look at licensing new products, new process approvals, process changes. All of those regulatory requirements do have a direct relationship to supply, and I want to talk about that a little bit.

Basically, a new paradigm. Security of supply is a safety issue. We think that's a very important safety issue. I want to talk about product availability and reimbursement under availability and security of supply.

First of all, product availability. Here's a little data to show that we are in short supply in some of our areas there. If you look at, for instance, the red line, the IVIG, we're about a half month's supply. That's an inventory-to-distribution ratio over time. You can see it's been bobbing along at a pretty low level, less than a month's inventory compared to ongoing distribution. And we get reports from a number of the consumer groups and from other evidence that there is a shortfall out there, and that is a risk to patients. There's no doubt about that.

So what are we doing about it? We have emergency supply programs. Every company has their own emergency supply program. We also are collaborating with the Immune Deficiency Foundation, for instance, on IVIG for their safety net program, and that's an important collaboration.

But those are temporary fixes. I think we have to look at things that grow our way out of this, and increases in capital expenditures, we're trying to expand capacity. There are a number of projects online for yield improvements as well. But, ultimately, regulatory policy has a play in this as well.

What we're looking for is regulatory policy that also considers supply as a safety issue, and specifically let's talk about what that means. Process approvals, new product approvals, INDs, et cetera, looking at those and saying: Is there a way that we can accelerate those approvals?

For instance, the FDA Modernization Act clearly does apply to biologics; it clearly applies to our products. And how can we apply that and make sure it's being applied, not minimizing or in any way damaging safety, but assuring that we're doing things that have good returns on safety and at the same time help to assure supply? It's that balance, and that's what we're trying to look at.

The other one is on GMP compliance, doing things to improve compliance, therefore further stabilize the supply environment and the production environment.

FDA is looking at a number of these things. We are working with FDA on some of those. There is going to be a GMP workshop coming up here in May to try to further train and give guidance on GMPs. All of those are important initiatives, and we look forward to trying to contribute value to that effort with FDA.

Reimbursement is something that doesn't get talked about a lot, but I think it's a critical supply issue, and basically what we could say is that therapies that can't be accessed due to inadequate reimbursement are of little value to consumers, providers, and, for that matter, companies. So some of the key issues that are out there are insurance caps. We know that a number of the patients that utilize these products run out of available insurance payments because of the cost of the treatments over time, and so they wind up either having to get shifted Medicaid or becoming indigent or just not being able to get the product.

There's a proposal out by HCFA. It's called the Outpatient Prospective Payment System, and it would say that any treatments in an outpatient setting would be reimbursed for infusion at $73.98. That's for services, the hospital, and the product. Infusion of IVIG can often be over $3,000. So compare $73.98 to $3,000, I think we have an entire disconnect here, and it's unrealistic. So you can see how the policy of one arm of HHS could come up with a proposal that could greatly impact the safety of the patients.

Provider compensation. When people talk about compensation and relative scales and things, we ought to make sure that as those are getting adjusted that the physicians and people that treat these patient groups are not disadvantaged in some way as to discourage them to go into this area or to diagnose or to treat these symptoms.

Price control legislation. There are several legislative initiatives in the Congress that we're very concerned about that would, in fact, ultimately discourage investment in R&D, discourage production, discourage investment in supply and expanded capacity.

As a matter of fact, I want to point out, too, that this isn't just our industry's concern. The consumer groups, consumer representatives, were very concerned about this as well. In fact, just this week there was a coalition formed called TAC, the Therapeutic Access Coalition, and all the major representatives are involved with that with industry and hopefully with some of the physician groups as well to address these issues directly.

So what's the path forward? We want to continue R&D, as I said, and capital investment. We want to try and grow our way out of this. We want to optimize regulation, balancing safety and supply. Increasing stakeholder input would be very helpful. Continue in our efforts on GMP to improve the GMP environment, consider supply as a safety issue, and then ultimately we're looking for an adequate reimbursement environment. I think by doing that we can help to assure the safety of supply. We already have done a lot to ensure the safety of the product.

That's it. Thank you.

DR. CAPLAN: What I think we'll do here is open the floor for questions for either presenters.

DR. CHAMBERLAND: I have a question for Mr. Reilly. As part of the qualified donor program, there's a requirement for two donations before plasma is used, and it's obviously an attempt to try and address potential window period issues. And you mentioned that there's a maximum interval of six months by which a donor would have to be requalified.

Is there on the other end of that a minimum interval during which time these two, number one and number two, donations can be collected? Is there some sort of requirement in days or weeks of--

MR. REILLY: There is, and I think it needs some explanation because it's not so much an effort to try and directly close the window period per se or create, if you will, almost like a quarantine environment, as much as it deals with the general psychology of donor participation in the program. Similar to asking the health history questions, it's not as definitive, if you will, as a test.

And what we found when we looked at the data was the mere act of a donor returning for a second donation indicated participation in the program and substantially improved our confidence in that donor's integrity as an individual.

So the minimum is basically the FDA regulations, and for source plasma that's a two-day interval. But as I said before, our experience was that 95 percent of all of our positives were in those individuals that came in once and we never saw them again. So that mere act of returning was what we were looking for.

DR. CHAMBERLAND: Have you actually been able to analyze what the observed interval is between the first two donations? If it actually can be separated by just two days, what in practice has it turned out to be?

MR. REILLY: I don't know.

Jay?

DR. EPSTEIN: Also for Jim, the data that you showed on the rate of retrieval of certain units based on the 60-day hold, were those theoretical estimates based on the window period, or were those empirical data based on actual seroconversions and then identifying the number of prior collections interdicted?

MR. REILLY: Our initial investment was theoretical, but we went back and looked at actual lookback reports and were able to demonstrate that they were accurate.

DR. EPSTEIN: So which did you show us?

MR. REILLY: I showed you the end--the actual.

DR. CAPLAN: Fernando?

DR. GUERRA: A couple of observations and questions.

From your presentation this morning and certainly from some of my own observations as a health officer in an urban center, I've seen your industry go from what was a rather disgraceful set of circumstances to what today is certainly close to the edge of technology and also just, you know, the physical facilities that I have seen undergo a tremendous transformation.

In the process--and I think that the population that participates in an ongoing basis as donors has probably also changed considerably for a variety of reasons. But what I haven't seen happen consistently is the reporting of individuals, especially in a private and confidential way, to assure the security of the information, that have conditions that are screened for and that are identified and that potentially have significant public health consequences in terms of a system and/or standards that go along with that to report to local health departments so that we can also track that population, that in many instances is really not connected to systems of care after you screen them out.

What are the policies that you have in place and/or the standards of care for dealing with the human side of all of this?

MR. REILLY: The policies we have in place are consistent with the FDA regulations and with the local authorities. One of the complexities that we have had to deal with, most of the companies operate multiple facilities across many states, and different states, particularly in the late '80s, as HIV sort of unfolded, if you will, on us, different states took very different points of view about report, don't report. Some were very adamant: we absolutely don't want to know. Others said we absolutely do want to know. So we have had some problems with just inconsistency within our systems in complying with the rules.

It is an area that I think we are increasingly concerned about. We have a medical directors committee, for instance, that is very actively looking at questions of donor screening up front as well as donor counseling downstream, if you will, when we have a seroconverter, and how to adequately counsel them and adequately refer them to the appropriate public health authorities.

I don't have a definitive answer for you that we do X everywhere consistently in and out. But it is an area that we're concerned about and is an area that I think you'll see us continue to make strides in.

DR. BUSCH: Jim, also for you, I also applaud the industry. I think the safety measures that you've introduced are phenomenal in the last few years, and the cooperation and collaboration and willingness to share data is great.

I do think that this transition to this--the distinction between applicant and registered donors, I think it's important, but I'm not convinced that it's absolutely had a fundamental impact on underlying risk, which is predominantly due to incidence rates. And I think to get at that, we need to really understand better the transition from an applicant to a registered donor. Data from that screening may be useful.

But a lot of the analyses that you show now, you're strictly focusing on the registered donor and have kind of moved away and, if you will, ignored the rates in applicant donors. And I was glad to see on one of the last slides that you do intend now to look back and monitor rates, both overall and demographics in applicant donors. I think there's going to be some very important information coming from that in terms of the kind of people coming into your system. And then further studies could determine whether that the people who do convert, studies could determine the incidence in the applicant donors underlying the prevalence and allow for comparisons of incidence in applicants versus the registered donors to see whether that transition really has reduced the risk. And I'm not sure it has.

From our own industry perspective, I think we've learned that first-time donors are not that much different in terms of underlying risk than regular repeat donors. Something that sort of surprised us.

But Fernando's comment, though, and related to this, is the issue of confirmatory testing in your first-time applicant donors. And I'm disturbed that it seems like your industry has not done confirmatory testing historically, routinely on these first-time donors who are reactive. You have had to do that adjustment factor and things like that.

And, in truth, in our industry, the whole blood sector, my industry as well, does not require confirmatory testing for all of the infectious agents, and in this cost containment era, some blood centers are not doing what would be in the interest of the donors, the appropriate confirmatory testing. Both for your industry and to FDA, I guess I'd say I'd like to see a mandatory implementation of confirmatory testing so that these donors can be appropriately notified, plus then we'll have the data to look more appropriately at demographic correlates of prevalence.

MR. REILLY: Just to address the confirmatory, I didn't sense there was an underlying question as much as a statement in the others. But on the confirmatory testing, we have actually made some strides there. I had to make the adjustment in the data because the other data was, if you will, historical, pre-confirmatory testing.

At this point in time, although it is not a QPP standard, per se, as an industry, we have made the decision to perform confirmatory testing on all donors, applicant and qualified. So, hopefully, as we look into the future, we will be able to then analyze that data as appropriate.

DR. HOOTS: Mr. Jackman, you mentioned the proposed HCFA Prospective Payment Grouping Reimbursement plans. Is it the strategy of IPPIA to approach HCFA not to implement the strategy or do you have a strategy that you are asking them to carve out reimbursement for the expensive products produced by you and for the target populations?

MR. JACKMAN: Well, the first strategy is to go to HCFA and say it is really not let's just say it's not a well-structured approach, methodology, the assumptions that are used in the methodology to come up with these cluster costs. Somehow they have come up with $74 for an average infusion. That not only impacts our products, it impacts a number of other products in the biotechnology area and are inadequate.

So there are other groups that are also opposed to this. So the first thing is going to say we think your methodology it's broke, and it's hard to fix. And I think MedPAC has also indicated that they have some concerns about this as well.

Ultimately, though, we would like to see consideration, if this were to proceed, that there be some kind of carve-out or something that would address the fact that we have chronic-use patients with high-value, but costly products, and somehow that has to be accounted for, whether it's outliers, et cetera.

By the way, even under the Balanced Budget Act, the Secretary of Health and Human Services has the power immediately to just basically say we are going to scratch out this whole group of products and not put them under Prospective Payment System. She has that authority under the Balanced Budget Act. So there is an opportunity for her to do something about this. But right now we are trying to approach HCFA, and we are working with a number of people in trying to do that.

DR. KUHN: Mr. Jackman, I was really interested about the HCFA reimbursement and how it affects the supply and access and especially these reimbursement issues like 73 cents. Is there a program or are you all in the process of educating HCFA about the progressing reimbursement issues so that it would help them to understand that there needs to be an equitable reimbursement of these products and services?

And then, do you think that this is the committee that may be able to help in that area to make recommendations or should we look into that further?

MR. JACKMAN: Yes. I think on that latter point, I think it's very important for this committee to look into it. The title of the committee, of course, is the Committee on Blood Safety and Availability. I think these reimbursement issues directly address availability. Inadequate reimbursement means that they are not available to patients, and this is both Federal policy, and it's also State policy and private insurance policy.

But what Medicare does, and what Medicaid does and what HCFA does, really has a tremendous ripple effect through the entire health reimbursement system. So I think it's critical to address this.

We are going through and trying, as I said, to meet with HCFA, to meet with MedPAC. We've had some meetings with some congressional folks as well to talk about our concerns with this.

DR. CAPLAN: I had two questions for either of you who cares to answer. One is if, for materials collected, not QPP now, without the UL label and so on, what happens to that material? One of the things that the committee has been concerned about is, in the face of shortage, there may be roads or routes for that material to re-enter, so to speak, the supply end. That's is question one.

Question two is would either of you care to speculate on--just a rough guess-what the cost has been on products for implementing this increased safety approach under QPP, having raised 10 percent/20 percent?

MR. REILLY: Let me start with the first question, and then I'll have to maybe do some quick math to figure out the second one.

On the first question, with regard to material that is not QPP-certified, it, frankly, falls into, for the most part, one of two categories, so there is not much waste that you are going to be able to recover there, if any. The first category being centers that are fairly exclusively collecting for diagnostic purposes; in other words, noninjectable products. Because most of these standards are aimed at trying to improve the safety of therapeutics or injectables, some of the diagnostic centers have simply said it's just not that relevant for us. So that material is being used already.

The small number that would fall into therapeutic products, if you will, is really mostly centers that are in the process of applying. The point at which they open their doors and the point at which they get QPP certification is not instantaneous. Although we may apply it retroactively, we don't count them in the numbers until it is done. So there, frankly, isn't very much that is not QPP certified when you look at the total value.

With regard to the cost, on the source material side, I have never tried to figure out what it is as a percentage, so I can't answer that. I can tell you that, since inception of this program, we have tried to run some fairly rough figures, but a conservative number would suggest that we've spent probably, to date, I am going to guess in the neighborhood of $150 million or more dollars on the collection system.

Now, that doesn't include what PCR would cost us, which is, I am going to guess, could be as much as not another $150 million, but a substantial amount of money. It does not include the inventory hold. So those are in addition to.

MR. JACKMAN: Just to add to that, as I mentioned, the member companies for IPPI only buy QPP-certified plasma for production of therapies in the United States.

DR. HAAS: Are there factors other than the Government-imposed testing that is impacting the supply? Are there any problems with getting donors or anything else?

MR. REILLY: On the collection side, the supply, I guess I would be happy to say that the supply maintains a relatively delicate balance between what we are collecting and what the fractionaters are capable of manufacturing. We have had a little bit of downturn in this past year by probably the same basic factors that are affecting blood collection. Society is changing on us, and people are busy, and for us within the paid donor it can't be ignored that the economy has an impact as well. But we have been able to maintain balance.

I think if we are concerned about things it is that, Dennis can show you trend lines that suggest that the amount of material necessary is going to go up, and up and up, and we are already in short supply. So as the manufacturing capacity goes up, we are really struggling with how to keep up with that increase or expect we will have to struggle. But as of today, on the source material side, it is not an issue.

MR. JACKMAN: I would just point that as we talk about process improvements, some of those are getting more efficient use of plasma and getting higher yields. So the faster we can move ahead with those I think that does improve and address that situation.

DR. GUERRA: What are the industry standards and guiding principles for recruiting or soliciting donors, prospective donors?

MR. REILLY: We don't have a document somewhere like a Code of Ethics related specifically to donor recruitment. What I can tell you, in general, if you had to try to envision one, anecdotally from the way that we operate, it's that we're interested in recruiting donors who will, one, be of the safest, if you will, from a viral transmission point-of-view quality that we can find, in an adequate supply, and that they will also demonstrate a commitment to the program.

We are much more interested in a donor who is going to come back not literally every day, but no less than a two-day schedule, but hopefully multiple times per month, where we can monitor their health, and we can get to know them, and our confidence in them goes up and up, and our supply then becomes much more stable.

DR. HOOTS: The surgeon general began talking, as one of his strategies this morning, global surveillance and the fact that we are globally integrated. And obviously the standards that you have start with the FDA basic standards and build on it.

Are there ongoing dialogues to extend particularly, say, to the EU, where the technology probably is comparable to what we have in the U.S., to begin to work in a collaborative way for these standards to mutually be implemented so that at some point, if the governments were to agree that the standards were meeting mutually satisfactory levels, that we would then extend the supply, as it were, since we've seen data in previous meetings saying that we're supplying a substantial amount of the world's requirements for plasma as it is, that we could kind of reverse that trend somewhat and draw from plasma from other sources outside the United States in a safe way to increase availability?

MR. REILLY: That question probably is better directed at FDA, but let me talk about an industry side of the question.

The ability to bring it back into the States is really FDA dependent. That part I will throw back to whoever might volunteer for it. From an industry perspective, as I said, we are already looking at how do we take these standards, not necessarily the line-by-line standard because the environment is different from geography to geography, but at least the principles of the standards, and expand the program so that all of the source material, all of the plasma that is coming in, is, we believe, of some kind of unified quality, supply, et cetera.

I think, in doing that, we have to recognize some of the different geographies. One of the frustrations, frankly, is what will get thrown back to FDA to answer is our program does assume a baseline of FDA rules and procedures related to that. And when we look at other geographies, in some places, there is a regulatory agency in place that we believe we have confidence in and establishes a baseline we are comfortable with. In other geographies, that is not as true. And we are struggling with, okay, how do we decide what's a competent regulatory agency, what's a comprehensive regulatory process that we can look at as a baseline.

So we are very concerned about that. We are not so much interested in being able to move product back to the United States, per se, although I think in times of shortages that would be very useful, we do have to recognize that we operate globally, and so we are interested in material that we can move from geography to geography, dependent on where the need is.

I think Dennis may want to add on the finished product side.

MR. JACKMAN: Yes. On the finished product side, we are clearly interested in efforts toward harmonization of regulation because mobility of therapies is an efficient way that you can adjust to varying demand and varying countries on a quick, quick basis. And examples would be where there are products available in technologically advanced countries such as Germany or Britain that then have to go through entire clinical process here, and the question is, is there a way to harmonize that somewhat to make it easier to bring those products over here. I'm not saying any lesser standard. We are not advocating that people, whether they are U.S. manufacturers based off-shore or foreign manufacturers, get in under a lesser standard, but that the standards are equivalent, and there's an equal playing field, and it actually contributes to availability of supply.

DR. EPSTEIN: Just a few comments about harmonization. There is an international effort for pharmaceuticals in general. It's mediated by a group called the International Committee on Utilization, which includes representation from the U.S., Canada, the developed countries of Western Europe, Australia, Japan. That group has not addressed blood products. There are other initiatives, but they are less-well formalized. The Council of Europe addresses blood components. That group provides a guidance document which is considered the reference standard for the EU. It was adopted as an official reference by the EU I think a year ago, and that does deal with standards for collection, in that it deals with things like donor screening and testing, as well as product quality issues. So it is an international standard in the sense that it is an EU standard, and you have multiple participating countries. The FDA participates as a liaison, as does Canada and New Zealand.

There is not as well-developed harmonization process for plasma derivatives, however. They are not primarily under the purview of the Council of Europe. They, of course, are regulated under the European pharmacopeia and the other EU authorities. Steps in the direction of international acceptance of standards have been progressive, but slow. I think that the current stage of the dialogue is negotiating mutual recognition agreements over inspections. So we are trying to work internationally toward an end point where if, say, the UK inspects a U.S. facility abroad, we might accept that inspection or conversely. We are not fully there yet, but those agreements are being negotiated bilaterally with specific countries.

Probably that is the most that can be said at this point. There is also an effort to harmonize application standards which is I think what you are alluding to. It's recognized that it's very costly to industry to have to deal with different application formats in multiple different countries, and the harmonization effort has gone a very long way towards standardizing the application. But each country still has its own discretion what constitutes acceptance. So there is not yet harmonization of the acceptance standards, which would then be the licensing standards and the commercialization standards.

So, again, it is correct that for the U.S. to import a product or even a blood raw material for manufacturing use, the foreign source would have to meet the U.S. standard. It would have to be U.S. registered, U.S. licensed, and we still do not have international standards for such things in the blood area.

DR. CAPLAN: Thank you. I think what we'll do at this point is take a ten-minute break.

Steve, did you have something you wanted to say?

DR. NIGHTINGALE: Yes. I just simply want to note for the record that all of the members of the Advisory Committee, except for Dr. Snyder and Dr. Schiff are now present.

DR. CAPLAN: We will reconvene and move into the discussion of ways we might enhance the blood supply with Marian Sullivan in about ten minutes.

[Recess.]

DR. CAPLAN: One of the problems that faces us, as we look at issues of safety and supply, is that the two obviously are interconnected, both through money and impact of steps to improve the safety of blood and plasma products who wind up having to make trade-offs. And obviously the committee is going to have a chance to talk some during the next few days about ideas it might have for advice about how to weigh those matters.

One thing we need to do is to have some understanding of what the current trends have been in blood donation and utilization. And to that purpose, we have asked Dr. Marian Sullivan, from the National Blood Data Resource Center, to talk to us a little bit about current trends in supply.

MS. SULLIVAN: Thank you. As always, I enjoy being referred to as doctor, but it's an unearned title.

Good morning, and I am pleased to have the opportunity to present here today data from the National Blood Data Resource Center's first Nationwide Blood Collection and Utilization Survey conducted in 1998.

This comprehensive survey of blood collection and utilization in the United States has replaced the American Association of Blood Banks' annual institutional questionnaire and a series of national surveys conducted by the Center for Blood Research since 1982. The NBDRC surveys will be conducted biannually, with the next one scheduled for distribution early in 2000.

Although the 1998 survey was designed to collect data to address a wide variety of issues of current relevance to the blood banking and transfusion medicine community, the primary objective of the survey was to establish national estimates for the collection, processing and transfusion of whole blood and blood components in the United States in 1997.

The method used was a 14-page mail survey distributed to 3,400 U.S. institutions. The sampling frame consisted of 149 nonhospital-based blood centers. We believe this to be 100 percent of all U.S. blood centers within the 50 States and excluding military sites, in addition, 1,841 AABB-member hospitals and 1,410 non-AABB-member hospitals. This was a stratified random sample from the AHA database of hospitals which we felt were likely to transfuse blood based on their annual surgical volume. Together, the two hospital groups comprised over two-thirds of all U.S. hospitals likely to transfuse any blood.

The mail survey was distributed in February 1998, and reminder postcards were mailed in April. A low response rate among the non-AABB-member hospitals prompted us to mail a two-page, short form to all nonresponding hospitals in September. The short form collected only the minimal quantitative data that we needed to achieve representative national estimates.

Phone calls were made to the few nonresponding blood centers in October and, finally, data entry and analysis were conducted by Westat, Incorporated, as well as many other study-related activities.

The response rates in the three groups were 99 percent for nonhospital-based blood centers, 81 percent for AABB-member hospitals and 51 percent for non-AABB-member hospitals, of which about 250 of the 715 respondents in the third group completed the short survey.

This map indicates the number of blood center and hospital respondents within each Public Health Service region of the United States. The blue number on the top representing the blood centers and the lower red number the hospitals. Alaska and Hawaii are included in the Pacific Region. When I don't say that, somebody always criticizes me because they don't seem to appear.

The data which I am going to present here today will be limited to whole blood and red-cell collection and utilization data. I apologize for this slide. The committee's handouts probably provide a clearer contrast.

I will tell you the column headings. The first column of numbers is blood centers; then hospitals; then the total, with the 95-percent confidence interval below it; percent of collections and the percent change from 1994.

And the row headings read: Allogeneic, autologous, directed, total supply, rejected on testing and available supply.

This table provides statistical estimates for whole blood collections derived from the data after imputation of missing responses and weighting of the hospital data to account for nonresponse. Confidence intervals are provided in parenthesis.

Total allogeneic units collected, not including directed, equaled 11,741,000, 93.3 percent of whole blood collections, and it changed from 1994 of negative 0.2 percent.

Autologous collections equaled 643,000, 5.1 percent of collections, a negative 36.5 percent change from 1994. Directed units equaled 205,000, 1.6 percent of collections. Directed units decreased by 38.6 percent from 1994.

The total supply was 12,602,000, a confidence interval of 222,000. This is a 5.5- percent decrease from 1994, and it translates to 700,000 fewer units, and more than half of those 700,000 fewer units can be accounted for right here in these two cells, blood center collections of autologous and directed donations.

This row indicates test loss, total lost to laboratory testing, 232,000 units rejected, a test loss percentage overall of 1.9 percent, which is a negative 45.7-percent change from 1994. I will talk about this a little bit more in the next slide.

Finally, the available supply of units that passed all laboratory screening tests was 12,370,000, a decrease of 4 percent from 1994.

The total number of units rejected as a result of laboratory screening tests was 232,000, with a confidence interval of 6,000, or 1.9 percent of all allogeneic units. In 1994, 432,000 units, plus or minus 14,500, were rejected, which was, at that time, 3.5 percent of the allogeneic supply. The decrease in units rejected of 45.7 percent from 1994 to 1997 was highly significant. Some of the recognized factors that are likely to have contributed to the change in test loss percentage were the elimination of the ALT testing requirement by the AABB standards in 1996 and the increase in the cut-off for some institutes and the ALT cut-off for those institutions that chose to retain ALT testing. To illustrate this, in 1994, 53 percent of all test loss was due to elevated ALT. Over 200,000 units, which nearly matches the total test loss for all tests in 1997. In addition, I should also add that no new screening tests were introduced in 1997.

The next two slides provide data regarding donations specifically from first-time donors. The median percentage of donations made by first-time donors reported by blood centers in this survey was 20 percent. Median percentage reported by hospital-based collection sites, of which we had just over 500 reporting in this survey, was 21 percent. The combined median was 20 percent donations from first-time donors.

Shown in this graph are the percentage of donations by first-time donors among reporting blood centers in dark blue and collecting hospitals in the lighter blue. While 56.2 percent of all blood centers collect blood from a donation base having 20 percent or less first-time donors, donations from first-time donors exceeding 40 percent are drawn by 7.3 percent of U.S. centers. The distribution of donations from first-time donors at U.S. hospitals is bimodal, with approximately one-third having few first-time donors and slightly less than a third using first-time donors for more than half of their collections.

This slide illustrates the relationship between the percent of donations drawn from first-time donors and test loss as reported by 94 blood centers. For each group of centers within a given range of donations from first-time donors, the median percent test loss was calculated. This value varies from 1.3 percent for centers with, at most, 10 percent of donations from first-time donors, which is the first bar, to 4.4-percent test loss for centers with donations from more than 40 percent of first-time donors.

Turning now to the transfusion side of things. Again, I apologize for the slide. The column headings are blood centers, hospitals, total, with confidence interval, percent of transfusions and percent change since 1994, allogeneic, autologous, directed, pediatric units, which are expressed as adult-equivalent units for comparison, total units transfused, outdates and unaccounted for.

One interesting change that we saw in the 1997 survey that was seen for the first time is that blood centers are becoming more directly involved in the transfusion of blood. Zero blood centers reported any transfusion volume at all in 1994. In 1997, 19 blood centers provided data for transfusions for which they were directly responsible, a total of 292,000 units.

The second column, transfused units reported by hospitals, totals 11,224,000, and the third column the combined totals for allogeneic transfusions, 10,929,000; autologous, 420,000; directed, 81,000 units to the intended donor. This was less than 1 percent of all transfusions from directed donations. However, it is important to note that 44 percent of directed donations were crossed over to the community supply, and that was a total of 91,000 additional units.

Going back up to the autologous. Autologous transfusions were 3.7 percent of total transfusions, and 65 percent of autologous collections were transfused to the donor. The percent change was negative 12.9 percent, which is not as dramatic as the percent change in autologous collections we saw on the previous slide. An additional 89,000 adult equivalent units were transfused as pediatric units, for a total of 11,517,000 units transfused. This is an increase of 3.7 percent from 1994, which is not statistically significant.

Six hundred and sixty thousand whole blood and red cell units were reported as outdated, a decrease of 11.7 percent in these outdates. Whole blood and red cells accounted for 31 percent of all outdates. And, finally, 1 percent of the available supply was unaccounted for by our data.

I prepared this slide to more easily summarize for you the disposition of whole blood and red cells in 1997. Ninety-five percent of collections were allogeneic, including both community and directed and 5 percent were autologous.

Extracting the allogenic portion of the supply allows us to further divide it, as shown on the right-hand side of the screen. Ninety-three percent were transfused, 2 percent were lost to screening tests, 4 percent were reported outdated and, again, 1 percent was unaccounted for.

Hospitals were asked to indicate the number of days in the past year elective surgery was postponed due to blood inventory shortages. 8.6 percent of hospitals indicated that elective surgeries were cancelled on one or more days due to blood shortages. There was no significant difference between blood collecting and noncollecting hospitals in this regard. The median number of days of cancelled surgeries for those hospitals that reported any was 2.0, and the range was 1 to 21 days. The mean number of days of cancelled surgeries for all hospital respondents was 0.44.

These data are difficult to interpret without additional information, and there are no nationwide historical data for trend analysis. The data do not appear to indicate any substantial national or regional inventory shortages for the year as a whole. However, we recognize that limited blood shortages do occur, but these are typically short-lived and geographically focused, and our survey was not designed to measure those types of shortages. In a few minutes, I will provide some additional data from another source to illustrate this point.

Hospitals reported a higher frequency of days in which nonsurgical blood requests were not met. 24.7 percent of hospitals were unable to meet nonsurgical blood requests on one or more days. The median number of days of unmet requests for those hospitals that reported any was 5.0, and the range was 1 to 365, and that was a huge outlier.

DR. CAPLAN: Marian, what kind of uses are those, nonsurgical?

MS. SULLIVAN: Nonsurgical uses, uses other than surgery.

The mean number of days of unmet requests for all respondents was 2.1.

In order to illustrate the fluctuation in red cell supply and demand, which our NBDRC survey doesn't address, I borrowed some data from the National Blood Exchange, which operates within the AABB. This graph displays the monthly listings of available red cells for the months of 1997. These are available red cells listed with the National Blood Exchange, and the upper line or blue line indicates requests made by NBE customers for red cells.

These data are limited to what's called the spot market or immediate requests made by telephone as opposed to those units that are shipped in response to standing orders. The pattern shown here for 1997 is typical of the seasonal fluctuations in supply that occur with red cells being in relatively short supply in mid-winter and throughout the summer and, correspondingly, the greatest proportion of unmet requests occurring in the winter and mid-summer months, January and June.

Returning now to the data from the Nationwide Blood Collection and Utilization Survey. The supply of screened whole blood and red cells that passed all tests, 12,370,000 units, exceeded transfusions of whole blood and red cells by a margin of 853,000. These data indicate that, nationwide, the available supply of blood in 1997 was sufficient to meet overall transfusion demands.

The remainder of my presentation will provide somewhat of a historical perspective for the adequacy of the blood supply, drawing from data reported from 1982 through 1994 by the Center for Blood Research and some previous data from NLBI and, finally, extrapolating recent trends in blood collection and transfusion to the year 2000 in an attempt to predict whether the supply will continue to meet the demand for blood.

Whole blood collections are placed in historical perspective on this slide. Total whole blood collections dropped to a decade low in 1997, declining 11.3 percent from 1987. During the same period, allogeneic units, including both community and directed donations, decreased by 12.4 percent.

Autologous donations, however, increased. That is the blue line, which you can barely see on this slide. Autologous donations increased 175 percent between 1987 and 1992, followed by a 41.8 percent decrease from 1992 to 1997.

The steepest increase in autologous donations paralleled the most significant drop in allogeneic collections which was observed between 1989 and 1992.

As I said previously, the decrease in autologous donations between 1994 and 1997 specifically accounted for more than 50 percent of the overall drop in whole blood collections for this period.

This slide illustrates the trends in the estimated rate of whole blood and red cell collection in the U.S. from 1971 through the present survey. The rate of collection was calculated from the total whole blood collected per U.S. resident population aged 18 to 65 for each survey year. Each point includes the 95 percent confidence interval for the estimate. The 1997 rate, right here, which is 72.2, was the lowest recorded since 1971, which was 75 per thousand.

The 1997 blood collection rate was 2.4 per thousand population lower than that reported for 1994, which is not statistically significant. However, the declining trend in the rate of whole blood donations in the U.S. over the past decade is of concern.

The 1997 red cell transfusion rate, 43.0 per thousand population of all ages, seems to indicate a stabilization of the transfusion rate after peaking in 1984 at 51.8. In 1994, the transfusion rate was 42.8. So essentially it hasn't changed since 1992, actually.

In order to provide a projection based on recent national estimates of collections and transfusions of what the supply and demand for blood might be in the year 2000, we have made the following assumptions:

One, the decline in total whole blood collections will continue through 2000 at the same rate as that observed between 1994 and 1997, a negative 5.5 percent over 3 years.

Secondly, the percentage of allogeneic units discarded as a result of laboratory tests will remain at or near 1.9 percent.

Third, no additional donor deferrals will be applied.

Fourth, the increase in total number of whole blood and red cell units transfused will continue through 2000 at the same rate as that observed between 1994 and 1997, 3.7 percent over 3 years increase.

Based on these assumptions, we have made the following straight-line projections of the available supply in 2000, which will be 11,694,000--you see available supply is the blue line--11,694,000 units. Similarly, the transfusion demand is projected to be 11,943,000 units or 2.1 percent less than the projected supply in the year 2000.

The 1998 Nationwide Blood Collection and Utilization Survey data which I have presented support the following conclusions:

Whole blood collections continued to decline in 1997, however, the number of allogeneic units collected did not differ significantly from that reported for 1994.

Secondly, whole blood and red cell units transfused increased slightly in comparison to 1994.

Significantly fewer units were rejected due to abnormal screening test results.

Five percent of allogeneic whole blood and red cell units were outdated or otherwise unaccounted for.

Less than 7 percent of the total available supply of whole blood and red cells was unutilized. Six, although fewer than 10 percent of hospitals reported any cancellation of elective surgeries, 25 percent experienced one or more days in which nonsurgical blood needs were not met.

Seven, neither the rate of collections, 72.2 per thousand, nor the rate of transfusions, 43.0 per thousand, changed significantly from 1994 to 1997.

Eight, the available supply. Both whole blood, and red cells and non-red cell components data which were not presented today was sufficient to meet 1997 transfusion demands.

And, finally, if the trends in whole blood collection and transfusion measured in 1994 through 1997 continue, the demand will exceed the available supply by the year 2000.

Due to the minimal size of the NBDRC staff and the magnitude of the study, we depended heavily on the assistance of many experienced volunteers in Westat, Incorporated. Shown on this slide, are some of the individuals to whom we are indebted for their contribution to this project.

Before closing, I would like to say one more thing about the NBDRC. We are an independent not-for-profit subsidiary of the AABB. The collection and analyses of the data presented here today were funded entirely by NBDRC membership dues and the support of the AABB. Most of the data from the 1998 Nationwide Blood Collection and Utilization Survey are available only to NBDRC members and customers.

In the absence of external funding for this nationwide survey, controlling the distribution of the data is the only way that we can ensure the future of the NBDRC. However, we do feel that it's our responsibility to make some data, particularly those that address issues of safety and adequacy, generally available to policymakers and other stakeholders. We do request that the data which we have share with the committee today not be redistributed without the permission of the NBDRC. Additional data may be obtained by contacting the NBDRC directly.

Thank you.

DR. CAPLAN: Thanks, Marian. In the interest of time, why don't we do like three or four questions. We are going to have some more presentations on the supply issues, but let's open the floor up for at least three or four.

DR. EPSTEIN: Marian, that was extremely helpful and very refreshing to see that these data are being gathered and analyzed.

Just on the question of autologous, there was a significant decrease in collections. How did that affect the rate of utilization of autologous?

MS. SULLIVAN: I believe the decrease in--

DR. EPSTEIN: Or the percent that was used versus discarded.

MS. SULLIVAN: I think approximately 300,000 fewer autologous units were discarded in 1997 compared to 1994. There was a decrease in usage of 12.7 percent, but 300,000 fewer units were collected. So approximately 300,000 fewer autologous units were wasted. A crossover of autologous units, which I should have mentioned, was less than 1 percent, about 5,000 units.

DR. CAPLAN: Jim?

DR. AuBUCHON: Marian, is it a fair projection that your analysis of the adequacy of the blood supply in the year 2000 is on the more optimistic side than the more pessimistic side, in that you showed, at the moment, or 1997, an apparent "excess," of 700,000 units. However, a large proportion of the units that would have outdated and would have been listed in your excess were group AB and would not have been generally transfusable to someone else. They just will not be available for use. Also, a fair number of that total related to autologous units, which, again, would not be used by an allogeneic recipient. Therefore, there may be less excess in the system than the first pass through your numbers may indicate.

MS. SULLIVAN: That's a good point, and that's why I chose to call it "apparent" surplus. Also, I would like to add that we don't have any statistical modelers at the data center. So in doing our projections for 2000, we did it very simply, didn't include a lot of population factors and factors of blood types and other factors that would need to be considered in a true model.

MR. ALLEN: Yes, ma'am, I was just wondering, since you have this data, has your organization worked with other groups to determine a way of increasing donations or has any of that come out of these results here?

MS. SULLIVAN: Well, actually, these results have just become available in the last 4 weeks or so. So very recent data. We are beginning to release the data, as I said. Obviously, we work very closely with the American Association of Blood Banks who makes a tremendous effort in the area in which you are indicating.

DR. KLEIN: I just wanted to follow up, in part, on Jim AuBuchon's issue, and that is that to say that the supply was adequate I think is an oversimplification because blood does come in groups, and in many areas it was not adequate simply because you can't give one group to a patient in another group.

In addition, the issue of inventory is a very important one because when you have a busload of patients injured, unless blood is immediately available from all over the country, the fact that you have an excess of a couple of hundred thousand units over a year's period of time does not equal adequacy.

I think the real question is did the nation collect about what it needed and could it easily collect more or did it collect as much as it could? It had a surplus of a couple of hundred thousand units, but not necessarily with the appropriate blood groups or in the right place at the right time at the right time of year.

MS. SULLIVAN: Exactly. Thank you.

DR. CAPLAN: We'll do one more. Keith?

DR. HOOTS: I know this was a trend analysis, but is there any data about the relationship between age of the recipient and predicted need for PAC cells or for any component unit? And has anyone tried to do any modeling of that? As the U.S. population ages, what will the impact of that also do on requirements and on supply?

MS. SULLIVAN: I am obviously not the best person to tackle that question. Jim?

DR. AuBUCHON: The only numbers that I remember, Keith, are now about a decade old. It was the United States Office of Health Technology Assessment, I believe, about a decade ago looked at that, and they noted that, at that time, about half of all blood was being transfused to individuals above age 65. So as the population grayed, there would be more potential recipients and fewer potential donors. At that time, which I believe was late '70s/early '80s, they estimated that there were approximately eight qualified donors, qualified on the basis of health, in the United States for every recipient and that that ratio was going to drop to three to one by the turn of the century. I may be slightly off on the numbers. But in other words, we can see the brick wall ahead of us.

DR. GOMPERTS: I have a trend question. Looking over the years '94 through '97 and the percentage of whole blood collections from the blood centers versus the blood banks at hospitals, is there a change?

MS. SULLIVAN: There was a very apparent change, a decrease for the most part, in blood center collections as opposed to hospital collections. Hospital collections decreased very slightly and almost entirely in autologous units, about 100,000 fewer autologous units, and that was the only decrease on the hospital side. The rest of it is all in the blood center side.

DR. GOMPERTS: Thank you.

DR. CAPLAN: Thank you, Marian.

Next, we have Dr. George Schreiber from Westat, who is going to talk to us about the frequency of blood donation.

DR. SCHREIBER: When Paul McCurdy asked me to present some data on the frequency of donation, I am always awed to come to a group like this because I am relatively new to the neighborhood of blood safety. And it's been through REDS that I have been involved the last nine years. So I am just a simple epidemiologist who just loves numbers. So you will see these slides have a lot of numbers, and there is a lot to digest.

I have been helped on this presentation by Simone Glen--Dr. Glen--and Anna Sanchez on the REDS staff. What we have tried to do is look at the frequency of donations and donation patterns in the country.

One of the interesting things that we did look at first was the 1993 NHIS, the National Health Interview Survey. And this shows basically that about 53 percent of the population never donated blood, and this is a number that we all know and are familiar with. We also looked at last year, at this age supplement, about 20,000 was available is 1994, and the numbers are almost exactly the same. It just happened that we did have this slide available.

And only about 5 percent of the population donates in the current year. And when you ask them if they are planning to donate again, as you expect, it's those who did donate recently who say that they are going to come back again. Now, there's many a slip between intention and reality, but at least the intention is here, and you see that those who never donated don't have any intention to really ever donate. So that if you are going to try to reach the "never donors," it's probably a lot harder to try to get them to donate than it is to increase the ability of people who have donated before.

The longer you wait between the time when you donate and you come back again, the less likely it is that you will come back again. So it is not really surprising, but I just put that up there to reinforce what we all know; that we have a limited pool, and for some reason, a lot of the population has, at one time, almost 46 percent, donated blood, but we lose them. We lose them probably because of health reasons, but we also lose a lot of people who have come back and donated once and that's it; first-time donors who come back, and they try once and never are seen again. So, for some reason, we are not very successful in getting all of the people who have tried to continue to donate blood.

The aim of this talk is to try to characterize the donation patterns among subpopulations of donors based on the REDS' collections in 1995 and then to use these numbers to try to predict what we could do to increase the donation frequency.

The REDS centers are the five centers: three Red Cross Centers in Oklahoma, Westat serves as the coordinating center, and this is a long-term commitment of funding through NHLBI, who has really made resources available to do a lot of interesting things concerning blood safety and availability.

We used the 1991 to 1996 REDS donation database for this analysis, which is about 8 million donations. And this analysis we have restricted to those who gave community donations during the study period. So we have taken out the aphoresis people, which is about 5 percent of the population. We haven't looked at those, which could be done for another analysis, but the numbers are small.

This is the characterization of the 1995. What we did is we looked at the types of donors. The first group that we have, and you will see, are the people who donated, and we call first-time donors, and this is their donation in 1995; they donated as a first-time donor, and that was their first donation.

Then we have repeat donors, and these are people whose first donation in '95 was a repeat donor, and they break down into two different groups; the inactive people and those who did not donate in the prior 12 months before their donation in '95. So what we wanted to see is how many people were repeat donors who, in fact, took some time off. In fact, they took out at least a year.

And then we have the active repeat, who donated in '95 and did donate at least once in the prior 12-month period. And those then we break down into repeat repeats, who are the first donation and then had a prior donation in '93--in '94--and then we have also the first-times who were first time in the 12-month period prior to their '95 donation.

Visually, this is what it looks like. These are the first-time donors who their first time was in '95. That is pretty simple. Then the repeat repeat, these are people who donated in the 12 months prior to their first donation in '95 and had donated prior in the 12-month period. Prior to '95 they had been a repeat donor.

The first-time repeat are people who, again, in the 12-month period had been a first-time donor and then come back as a repeat donor in '95. And then these are the inactives who sometime out here were classified as a repeat donor, but skipped donating in the 12-month period and then came back.

And the reason that we broke it down into these groups was the thought that if you are a blood center, perhaps if you are going to try to do an intervention program or a recruit program, you might tailor it differently to these different populations.

We had, roughly, 32 percent of the population that were first-time donors, and what we did is we are restricting the analysis from this point on to those who were seronegative on the first donation. So you can see we lose about 6 percent of the first-time donors who were seropositive for some market. So we have dropped these from the analysis.

Some of these people in fact do come back. These could be people that had an elevated ALT or something else that did not preclude them from ever coming back.

68 percent of the population are repeat donors, and you can see that 30 percent of them are repeat-repeat. 31 percent of them are people who are repeat donors who took off at least a year, and then we have the first-timers who had given a donation and are coming back as repeat donors. So we have about 550,000 donors in this 1995 period.

The first-time donors--this is the 164,000 who were seronegative--they gave their total of about 30 percent of the total donors. The small loss that you see of the 2 percent is because of those who tested positive on their first donation, and these donors gave about 24 percent of the total donations. Again, I am sure that these are figures that you all have in your blood centers and have seen. So these are not atypical of what exists out there in the community, and 74 percent are from repeat donors. And we have a total of about 824,000 donations from the 550,000 donors.

Now what we have done is we have looked at first-time donors to see what their donation histories are, and the "zero" means that there was no time between their first and subsequent donations. So these are people who did not come back, and you can see in 1991, which we have 5 years of history to go on, 50 percent of the people donate once and never come back as first-time donors, and 33 percent of them come back within the first year. Then the rest of them tail out.

In 1993, we only have 3 years of additional history to go by through '96, but if you drop these numbers down, that would reduce this 53 to roughly 50 because these people have not had enough time to come back over 5 years.

So what you see is, again, a consistent patent that first-time donors, only about 50 percent of them ever show up again, and of those who do show up again, if you do not catch them within the first year, you get very little return. So that, those who donated in one year and then came back 5 years later or 4 years later or 3 years later is an inconsequential number. So that, if you have first-time donors, then you have to have your intervention program or your recruitment program geared at them, and I think Dr. Piliavin mentioned this in her book. You have got to go out after them right away, and our numbers, you will see later, support this.

If you are going to intervene or try to design programs, here is a point where you can emphasize the importance for them to come back and also try to look at why they do not come back.

One of the future REDS surveys is trying to look at donor motivation to try to see what motivated people to come back and then why they will become consistent donors.

Now what I have done is looked at the impact and the frequency of donation on those four groups, and again, these are the first-time donors, and you can see, again, that within the first year--this is within a 12-month period of coming back--66 percent of the first-time donors did not return within the first year. Again, 50 percent never return. So that the extra 16 percent are people who returned within the first year.

You can see that the number of repeat donors within first-time donors is small. About people who came back two or three times, there is about 46 percent of them, and very few people come back a lot of times in terms of first-time donors. You will see that the pattern will shift a little for the repeat donors.

These are the repeat donors, and again, as you can see, about 31 percent of these people came back and only made one donation in the subsequent 12-month period, but there is 79 percent donated multiple times, and you can see that about 61 percent of the people made two or three donations within the 12-month period.

So, again, you can see that there is a tail here. And that people who donated four times, there is about 19 percent, and 10 percent donated five times.

This is really the wall here for these six- and seven-time people because you will never get them to come back again within another 12-month period because they can only give every 56 days. So they will not be eligible to come back. So that what you are really talking about is if you are going to have any kind of program, you are gearing it to those people who gave five or less times.

These are our first-time repeat donors, and again, you can see that about 50 percent of them never come back. The rest of them do come back a number of times, but the bulk of them are clustered in those who give one or two more times in the next 12 months.

We do have 13 percent of the total donations that are given by people who have donated four times. So that, you can see that these first-time repeat donors are more like the repeat-repeat donors. So they have gotten it into their soul that they are going to be repeat donors, and their pattern is starting to look like the repeat-repeats. So, at some point in time, they will be indistinguishable from those who were repeat donors.

The next group is the people who are the inactive donors, and again, you can see that those inactive donors, some of them came back, but basically they came back for one donation and do not show up again.

You have a number of them who then come back. About, whatever it is, 44 percent will make multiple donations within the next year, but, again, the number of multiple donations is really limited to the two and three times.

Now the next question is: Is there any gain in trying to go back after heavy repeat donors? Are they any safer? This is a frequency analysis where we looked at their donation patterns within 2 years, and we looked at how many times they donated within 2 years. We did an incidence analysis, and what I will show you in this next part of the analysis is that there is no additional safety for multiple donors; that they are no safer than those who donated one or two times. So what we are going against is the conventional wisdom that multiple donations make you a safer donor, and that is contrary to what we had presented a couple of years ago in terms of showing that people who donated a lot of times were safer.

If you look at, for example, the HIV, you will see that those who came back did not come back, had an incidence rate of about 2.95 versus those who came back five times, 1.38, but the trend is insignificant. It is nonsignificant.

So what this shows you is that there is no additional safety attributed to those people who donated more times. So that, if you are going to go back and try to re-recruit, you would re-recruit people who came back just as frequently in one or two times as you tried to emphasize those who donated five-plus times. So there is no additional margin of safety for HIV.

You will see this is the same for the other markers. For HCV, we have restricted it to the period of EIA-2, which is 392 to 696, and again, there is not trend in the increased safety with increased number of donations.

For the hepatitis B, in fact, if you look at just the surface antigen, which you know is a transitory marker, you would come up with a conclusion that those who are donating more frequently are less safe, and this is became the marker in fact is transitory. The more you come back, the more likely you are to pick them up.

So what we did is we did an adjustment looking at what period of detection and the inter-donational interval, and when you adjust for that, you see that there is on difference between people who come back infrequently and those who come back more frequently. The incidence rates are about the same.

The discussion of how you make this adjustment is probably another hour, and you have to take my part on faith that it is probably good. We did adjust by a factor in our incidence papers, and what we show here is that the adjustment is a function of the inter-donational interval and the period of detection of the marker, but in fact when you do take that into account, it wipes out this donation frequency, and at some point, people who come back very often.

So if you took, for example, some of the plasma donors, there you do not have to do any kind of adjustment because they are coming back very frequently, and their rates are what you would expect for the seroconversion rates.

HTLV, again, nothing exciting. It is a flat-out distribution. So that, we see that those who come back frequently are no safer than those who came back one or two times.

Now what we did is we built in some assumptions, and we took 25, 15, and 5 percent reductions in the proportion of donors who did not return within 12 months, following their first donation. Then we also assume that the frequency of the donations are Poisson-distributed. So that, if you looked at those previous donations I showed you, it was obvious that they were Poisson distributions, obvious to a statistician, but probably no one else in the world, and probably at this point, a lot of people are asleep and did not even think about it, but we are assuming that they are Poisson-distributed, and we are looking at what the impact would be in making small changes and then probably unheard-of changes of 25 percent in terms of bringing those people back.

I have two more slides here. This is a summary of all of the numbers that I showed you before of the distribution of donors by the group, and you can see that a lot of the first-time donors do not come back. You can also see a lot of the inactive repeats do not come back, and then you can see where these distributions tail off.

You can also see that the overall number of donors are about the same for the inactive, for the first-time, and for the repeat donors. If you sum these up, there is about 170,000 in these groups. So what you would expect is that any program would act about the same in those groups, and the next slide shows that.

Here are the first-time donors. Their average-donations-per-donor rate is roughly 1-1/2 per year. For those who are the repeat-repeat, as you know and expect, you get a much higher return rate, and the inactive donors who were repeat donors are really somewhat similar to the first-time donors.

Then what we have, using the Poisson distribution, if you have a 5-percent rate, a 15-percent rate, and a 25-percent rate, this shows you what the expected number of donations would be.

Now, the first thing you say is why isn't this 25 percent five times as much as the 5 percent, and that is due to a rounding error. The .1 here is really .05, which we rounded up, and this one here comes out to be really .29, which we round up to about .3, but these are not rounded. You see that what happens here is that the number of additional donations is about the same for the first-time, the repeat, and the inactive. So, because those populations are about the same, you would expect there to be an increase in this 15-percent rate of about 26,000 donations for a total of about 86,000 donations in this group. Or, in fact, if you had an extremely successful program or unheard-of program and could bring 25 percent of them back, this would give you a net in our population of about 156,000 donations.

What I did is I projected those out, given that REDS represents about 8 percent of the total donor population in the U.S. I projected those out, this 26,000 at a 5-percent increase rate, which is probably doable within a program. It would translate into about 337,000 additional donations in the U.S. if you could have an intervention program that would increase the number of people who came back by about 5 percent.

If you could jack that up to about 25 percent, which again would be an astronomical program, you would in fact almost bring back 2 million additional donations within the year. Somewhere between a 5- and 15-percent program, which would give you about a million donations here is probably something that is doable.

When you look at the types of programs that might be doable, that could be--and I am just projecting--that could be something as simple as giving donors a card that would appoint them to come back the same as the dentist does. So that, you made your donation, I gave you a card and said okay, you can come back in the next month, and they agree to it. You might be lucky enough to get a significant number of them to come back.

The fact that at last year's AABB poster session, there was one of the blood centers that was using an appointment scheduling like this, and they were very effective in bringing their donors back very quickly. In fact, they increased their number of donations very, very significantly.

In fact, what we are showing here is that if you have a program, you probably could increase by about 10 percent, the total U.S. blood supply, if you could bring them back, about 15 percent of the people, within the year who normally would not have come back.

How can you get that? Well, I will leave that to the behavioral scientists to see and tell me if in fact there ever is a way, but I think that there are probably steps that we could take that would be doable that would increase the population.

There are also other lessons that exist out there in some of the HIS information that I did not address, and that is that, for example, in HIS, among the people who did not donate, almost 40 percent of those who never donated believed that you could contract AIDS from the process of donating.

So, somewhere, there is a misconception among a significant number of people that donating itself is an adverse process. That process drops down. That perception drops down, so that those who donated more recently within HIS, there is only about 9 percent of those people who believe that they could get AIDS In 1993 by donating, and those who had donated after 1985, there is about a 30-percent chance. And those who donated as recently as 1989, that percentage drops to about 15 percent, but what there is, is that there is some kind of misperceptions in the community about risks associated with donating blood.

Now, why anybody would ever donate blood and think that there is a 9-percent chance of getting AIDS, it could be that there is a misperception of what the question is, whether there is a misperception of the reality, but in fact, in REDS in 1998, we found that there was about 3 percent from our survey that felt that you could contract AIDS through donating blood.

So somewhere between reality and misperception, there is something that we could probably do to tell people who are wrong that there are problems out there, which could in fact maybe increase their ability and increase the number of times that they would come back.

So I will stop there on these numbers, and if there are any questions, I would be happy to entertain them.

DR. CAPLAN: Let's open up the floor.

MS. O'CONNOR: I have two questions regarding how people are counted. When you talk about first-time donations, if people move from State to State and perhaps contributed at different types of centers, would they be then counted as a first-time donor or a repeat?

Secondly, if someone goes in to repeat and is rejected for, say, a temporary condition--maybe they have traveled to an inappropriate country or some medical condition--are they then not counted as coming back?

DR. SCHREIBER: In this case, first-time and repeat are first-time and repeat at that center because that is how the centers classify people, and that is the classification that we used. So that, in fact, you could be a long-time donor, move from New York and have been contributing to a New York blood center and go to Irwin and contribute for the first time. You are a first-time donor. After that, you are a repeat donor. So we look at what the blood center classifies them as.

If you are rejected at some point and come back, you are still maintained in that category. The only people who categorically do not appear again are those people who are rejected on the donation base as being something like HIV-positive, but someone is bouncing around with an abnormal ATL can come back. If they are rejected, then they cannot come back, and they are not counted again.

MS. O'CONNOR: With such a highly mobile society, I am wondering if we are over-estimating significantly the number of people who do not come back, and is there any way to ascertain that?

DR. SCHREIBER: We cannot through the REDS, through our donation database, and I have not seen any study that looks at the movability of donors, but when we look at the REDS donation database, people who came in, in 1991, a significant number of them are still coming back in 1996. So I think that, despite the people moving, there is a high percentage of people who come to a center within the catchment area of that particular blood center.

Certainly, there are people who move across the country, and certainly, there are people who move outside of that catchment area, but I think what we are seeing here is that there are a number of people who might move across town or move whatever there is away, but in fact, there are a high percentage of people who do not move within the catchment area of that.

So, for example, in the Chesapeake area, which is one of the ones in REDS, the overall catchment area contains parts of Washington, parts of Virginia, and parts of Pennsylvania. So that, there are a number of people who do move, but they stay within that ara, but I do not think anybody has looked at the question that you asked specifically.

DR. CAPLAN: Just when you ask questions over on that side, put eternity over politeness. If you talk into the mikes, it will get into the transcripts.

Other questions?

DR. GILCHER: George, your data is very important in questioning whether there is a difference between the first time and the repeat donor.

What I do ask, though, in looking at our own donor base, we have the third category that we call frequent repeat, and essentially, all of our frequent repeat fall into the apheresis group. Now, there are repeat in that group and first-time, as I will show or discuss later, but when we look at the frequent repeat in terms of incidence at a seroconversion, it is exceedingly low, making us still believe that that particular group is somewhat safer than the repeat or the first-time.

Can you comment?

DR. SCHREIBER: I think Simone Glen is looking at apheresis donors. I think Simone is still here.

There was no different, was there, in terms of frequency of donations for the repeat, or do we just not have enough?

DR. CAPLAN: Simone, do you want to come up and tell us in the mike?

MS. GLEN: The data that was presented for the incidence rate, that was on whole blood donors only. Actually, I do not think we have done exactly the same analysis with apheresis donors.

DR. SCHREIBER: But you did do some preliminary analysis on your apheresis and incidence?

MS. GLEN: Right, and there, there was no difference between apheresis and repeat whole blood donors for the incidence, but, again, the number of apheresis donors is rather small.

DR. SCHREIBER: There might be. We presented, and I have to admit egg on my face. A couple of years ago, we presented data looking at the frequency of donation at AABB, and that preliminary information looked like donors who came back more were safer, but then when we used the category that you recommended, did they come back within the 2-year period, that is why we have this 2-year period here. It looks like there is no relationship with frequency, and we have also looked at this. I mean, when you make a mistake, you try to look at it every which way just to try to recover yourself. We looked at it not only within a 2-year period. We looked at it within a 3-year period, and there is nothing. We looked at it within how many times they donate a year over a long period, and again, it looks like there was nothing related, at least for the whole blood donors. That was a definite trend with increased frequency and safety.

It might be within apheresis donors that there might be something that is there, but at least within the whole blood donors, no matter how we cut the cake in classifying them, it does not look like more frequent donors are safer.

Part of that is that we might not have a trend because the numbers of incident cases are low, and if we had a couple hundred of them, we might see something, but, in fact, that would still indicate that this is probably not something that is very dramatic because, if you have to go out and have hundreds and hundreds of cases and we do not see it with HCV and we do not see it with hepatitis B, which is more frequent, it probably is not something that is there that would be that more frequent donors are safer.

DR. CAPLAN: What I am going to do, just so you know what the agenda is, I think I am going to flip the talks, the remainder of the session. Dr. Williams has said this is okay, and we have a captive population with the other speakers after lunch.

I think it is fine to pursue some questions here. So let's do a few more. Then we will do the lunch break as it was scheduled on the agenda. Then we will come back pretty close to 1:00 and pick it up.

DR. McCURDY: There are a couple of brief comments that I might make. One is that the 46 percent that George showed of individuals from the NHIS survey, who had ever donated blood, is really quite close to the approximately 50 percent of the population, and a study done by Alvin Drake from MIT back in around 1978 or '79. So, the more things change, the more they remain the same.

The other thing is that the Red Cross, during the '70s and early '80s, maintained a national donor deferral registry of people who were permanently deferred as a result of history of hepatitis or a positive test or something like that, and they looked at the situation to see whether they really needed a national database or whether a regional database would be sufficient.

The number of hits on that database that came from outside the region that had the current donation were quite small, even in the Washington region, which was then separate from the Chesapeake region, and the Washington area is one of the more mobile areas of the country.

I do not remember what ultimately was decided about the DDR, but the fact of the matter was that the mobility from one region to another was not as large as people thought it was.

DR. PENNER: Just a comment. My experience would agree with Ron's that the attrition rate in the 5-, 10-, and 20-gallon donors is very low, and attrition being scribed primarily to death and not to eliminating them from the pool from having picked up some marker.

DR. CAPLAN: Keith?

DR. HOOTS: In terms of the denominator you used to calculate the 53 percent who had never donated, is that a U.S. population denominator, or has it been adjusted for people who would not have been eligible to donate to begin with, like in prison, permanently HIV or all that, and all the other adjustments?

DR. SCHREIBER: The population base is in the National Health Interview Survey, which is a random sample of homes, and I think there is 40,000 or 50,000 homes in the survey.

The blood ones are restricted to the people that got an AIDS supplement, and of that, there is only something like 20- or 21,000 that are over the age of 18. So that is what that 50 percent is.

We cannot adjust for anything. That is what NHIS does, but I think it is just a random sample of the population. So there is probably not a big prison segment in there, and about, I think, 85 percent of them are whites. So that, it is probably pretty representative of what the population of donors is in the country. There is about 6 percent or 7 percent that are black, and about 7 percent are Hispanics, overall in the country, I think, in terms of blood donors and the racial mix.

There have been some places in the country where we showed last year at the AABB where LA has been very successful increasing the number of Hispanic donors over the course of the last several years because they have mounted a very aggressive program to go after them.

I am sure there are other places in the country that have aggressive programs to try to increase recruitment of certain segments of the population, and it is the same thing. If you go out maybe and have a very aggressive program that deals with high school and college kids, then there is probably a chance that somewhere later in their lives, they will contribute more.

DR. BUSCH: Just speaking to Paul's point about where we are in the cross-system in terms of picking up any new donor that might show up in one of our regions, we do have a National Donor Referral Registry that we can use, which is about half the U.S. blood supply. So we are able to identify first-time donors, donors who do have some kind of referral category that we need to know. I think that has cut down the problem, at least to some extent, with people showing up at different regions in the country and not being identified with first-time status or some other status.

DR. CAPLAN: Okay, thank you.

Let's take our lunch break. We will reconvene here at 1:00.

[Whereupon, at 12:05 p.m., a luncheon recess was taken, to reconvene at 1:15 p.m., this same day.]

[1:15 p.m.]

DR. CAPLAN: I have got a request which I think I am going to honor in the interest of politics from the American Association of Blood Banks to make a brief statement because they have, I guess, a congressional hearing. So, if we let them go quickly, we can do that, and then we will go to Dr. Williams and move to our committee members, who are actually going to present testimony today, Mike and Ron.

So without further ado?

MS. WILKINSON: Thank you very much.

Good afternoon, ladies and gentlemen. I am Susan Wilkinson, president of the American Association of Blood Banks. Thank you for the invitation to address your committee today.

Most of you already know of our association. We are a private voluntary standard-setting organization. Our mission is to establish and promote the highest standards of care for patients and donors in all aspects of blood banking and transfusion medicine, hematopoietic cellular therapies, and tissue transplantation.

We accomplished this mission through our standards-setting and accreditation activities, as well as our educational programs. Our programs are directed to members of our profession, the medical disciplines we serve, and the patients and donors who benefit from the help to support transfusion medicine in the United States.

Our members include facilities that collect virtually all of the blood in the United States. We also count on our members, more than half of the hospital blood banks and transfusion services involved in providing blood to the patient recipients in the United States.

Today, I want to talk to you about a very important issue that is seriously affecting our mission. How are we as a Nation going to pay for safety?

The safety and adequacy of the blood supply are our primary concerns. The AABB was formed with these twin goals in mind. To the extent we knew how to protect the blood supply in the 1950's and '60s, achieving the goal of safety was relatively simple.

In the first addition of our standards for blood banks and transfusion services, the only serologic test we required was for syphilis. With the discovery that hepatitis could be transmitted through the blood supply in the '70s and HIV in the '80s, heightened awareness and implementation of new technologies have helped to increase the safety of the blood supply to the highest level anywhere in the world.

Today, our standards require serological tests for nine different biomarkers in the donor population. With nucleic acid, we were adding still more.

We have early earning systems through the FDA, the CDC, and the AABB Transfusion-Transmitted Disease Committee. These groups are continually on the lookout for new threats to the blood supply. The Federal Government, pharmaceutical companies, our members, and the AABB, through our national blood foundation, are investing continually in additional research directed at enhancing safety.

Safety first at the expense of everything else. Yet, we are operating under a Federal reimbursement system that has built into it every possible disincentive to improve safety. Here are some facts to consider.

Blood collection and transfusion in this country are performed primarily through not-for-profit organizations that were established to provide services to the community. As not-for-profit organizations, they operate on a cost recovery basis with little or no reserves.

Unlike the airline or pharmaceutical industries, which have also faced the need to invest in safety improvements, this community has virtually no access to capital or capital markets that are required if we are to continue to support further investment and expansion.

As a consequence, virtually all safety improvements must be funded by losses at the blood centers or increase charges for blood to the hospitals.

At the hospital inpatient level, blood collection facilities are not directly reimbursed for providing blood products or services. Rather, blood therapies are usually included as part of the total reimbursement the hospital receives for providing inpatient care. This reimbursement is usually determined prospectively based upon the patient's diagnosis-related group, and payments under this diagnosis-related group do not very, even if they costs incurred in caring for a particular patient are more.

Under this system, there is no opportunity for blood collection facility cost to be passed through for direct reimbursement.

Moreover, hospitals are facing critical financial situations. Under the Balanced Budget Act of 1997, Medicare cuts have almost eliminated hospital profits for Medicare.

Overall, hospitals are looking at a drop in profit margins from all revenue sources, from 6.9 percent to 3.6 percent in 2002.

A 4-percent margin is generally cited as the minimum to be able to maintain and replace facilities and equipment.

Medicare is the largest third-party payer. It drives what private insurers and managed care organizations will pay for blood-related therapies.

Under current operations, Medicare does not generally account for new technologies until well after the technology has been in place, and that assumes there has been a successful effort initiating by affected parties to add, change, or update a code.

Ambulatory or outpatient care, which is currently reimbursed on a cost basis, is the one exception, but as you are aware, changes currently proposed by HCFA would eliminate the cost-based reimbursement and drastically reduce the limited recovery currently available.

The statutory authority of HCFA to adjust in advance for new technologies has gone largely unused in recent years.

The average charge for unit of blood has remained relatively constant over the last 25 years, despite significant increases in the cost of safety.

In the late 1970's, with screening tests for only syphilis and hepatitis B in place, the average charge for a unit of red blood cells was approximately $35 to $40.

In 1998, with tests for seven additional viral markers, that same unit cost approximately $75 to $80.

Today, one year later, with the introduction of nucleic acid testing, the charge has jumped to approximately $90. In constant dollars, that $40 increase is really only $14.58.

There are no regulations governing distribution of blood. This community operates in a fully competitive environment.

Although blood centers and hospitals have worked to control the costs of providing safe blood, new generations of improvements, including leuko-reduction, nucleic acid testing, and viral inactivation will exponentially increase the cost of providing blood and transfusion-related services.

Current annual estimates for the cost to leuko reduce the Nation's blood supply range from 400- to $672 million per year.

Data suggest NAT testing will cost approximately $75.6 million per year.

Moreover, incorporating these additional safety features involve significant start-up costs as entire laboratories must be retooled or built and staff fully trained to accommodate these new processes.

The easily identifiable costs that must be covered do not tell the entire story. Safety of the blood supply, as we all know, is directly related to adequacy.

Every step to improve safety carries the possibility of decreased donations. As we discover new ways to screen donors, we invariably reduce the number of potential donors as we defer donors with specifically identified risk characteristics. The most unsafe unit of blood is the unit that is not there when you need it.

Data presented this morning from our NBDRC illustrate the real potential for life-threatening shortages if collections continue to decline and transfusions continue to increase. Again, the issue is one of cost.

Although the incremental cost of collecting a unit of blood from a donor who simply walks in from the street is virtually nothing, any donor recruiter will tell you that the true cost of identifying and retaining first-time donors is far more expensive than retaining committed donors.

Available data suggest that the average recruitment cost per unit donated is $11. Extrapolating from known recruitment cost and donor motivation patterns, the cost to obtain donations from first-time donors who must overcome initial fears about blood donation ranges from $15 to $30 per unit collected.

Moreover, finding donors with rare blood types, often needed to save a life, becomes even harder.

As an example of the potential impact, FDA is currently considering a policy that would bar donations from individuals who have traveled to the United Kingdom since 1980 to reduce the theoretical risk of CJD infection from blood transfusion.

It is estimated that such a policy would result in a deferral of approximately 11 percent of the present donor population.

Based on 1997 collections of 12.6 million units, 1.4 million units will have to be deferred and replaced to maintain a constant supply.

With an incremental cost of $4 to $19 to obtain replacements, the added cost ranges from 5.5- to slightly over $26 million.

The AABB is conducting a survey to confirm potential losses to the blood supply from the deferrals now under consideration. Whatever the results are, to the extent these donors are deferred, we expect to have to recover those lost units through additional recruitment resources.

With all of this, our concern is that the belt-tightening that has been going on for years has already cut out the fat. Hospitals are dropping AABB membership to avoid implementing our new quality system, and we have made the decision to subsidize that cost.

Our current charge to a small- to medium-size hospital is approximately $600, far short of the true cost to provide our accreditation and other services.

As a practical matter, the two things blood centers and hospitals have left to cut are fixed assets and staff.

As hospitals and blood collection facilities seek to survive, the immediate natural reaction will be to cut staff. Fixed assets cannot be easily cut.

Staffing and blood facilities is already critically low. With additional cuts, we can expect to see a different kind of safety failure. While we are relatively safe from known transmissionable diseases, more errors and accidents are likely to occur as overworked people make mistakes, accidents like transfusing the wrong unit or misreading the results of the sophisticated tests we now perform.

We have an unfunded mandate from the public and the Federal Government to make blood safe. We believe in the mandate. We always have, regardless of the cost. The real issue is not cost. It is who is going to pay.

As a recommendation to at least begin to address this dilemma, we ask that this committee review the issues carefully, but as quickly as possible, and call for rational Government policies to accommodate safety improvements as they come online.

For example, as FDA moves to require leuko-reduction of the Nation's blood supply, HHS should require HCFA to be prepared with a corresponding funding mechanism.

The same holds true for NAT and other, as yet, unidentified safety initiatives sure to follow from all of our efforts to put safety first.

For our part, the AABB has just agreed this week to initiate a full-scale effort to educate HHS, HCFA, Congress, the Federal Government, insurance companies, the public and our members about the critical nature of this unfunded mandate and the need to correct the deficiencies in the reimbursement system.

Leading this effort is a new AABB task force on reimbursement for transfusion therapies comprised of AABB members and representatives from the American Red Cross, America's blood centers, hospitals and other interested parties.

We hope we can count on your support to keep blood safe. Appropriate reimbursement is key to achieving this goal.

Thank you very much.

DR. CAPLAN: We have time for a few questions.

Susan, what is your read on the--how should I put it?--receptivity of Congress to this argument?

MS. WILKINSON: I would have a better answer for you tomorrow.

The AABB board of directors is currently on Capitol Hill this afternoon, and this is the message that the members of our board are communicating to Members of Congress. So I would be happy to get back with you on that question after today.

DR. PENNER: Just a quick question. How much do you think a unit of blood should cost?

MS. WILKINSON: I think a unit of blood should reflect is actual costs, whatever those may be.

DR. PENNER: Do you have a range? Would you think it would be worth $1,000 or $50?

MS. WILKINSON: It would certainly be more than $50.

I think, again, one would have to take into account what are the direct costs and what are the indirect costs that are required to in fact produce that unit of blood.

DR. PENNER: Just a comment. This is the biggest bargain we have ever had in the medical profession is the cost of blood.

In 1980, as I recall, it was about $43 at our institution, and it varied around at that point, and it has gone up maybe twice that.

A hospital bed in an intensive care unit, I think, is running around $1,200 a day or more. The antibiotics I used on my last patient cost me $1,000 a day for about a week, and yet, for the blood that we know is going to be very effective in a patient who is suddenly running out of blood and will allow him to survive, it is still going at under $100 for a unit, and even if you have to have several units, it is still such a bargain. It is hard for us to get out of the orientation that at least I have and some of my colleagues have for many years that blood should be, like donated blood, no cost at all.

We have, I think, an orientation that has to be changed, but this is something that we are going to have to accept the fact that there is a cost benefit that is worth it, and in comparison to the rest of the additives that we are providing in medicine to maintain our patients, that this is still a super bargain and we ought to be willing to pay the additional amounts that are for it.

Thanks.

MS. SECUNDY: Ms. Wilkinson, for clarity, might I suggest that when you talk about costs per year, incremental costs and added costs, and then you talk per unit, it would be helpful to me if you could clarify what the annual costs that you are projecting will do to the unit cost.

For example, item 6 and item 7 are the areas that I am talking about. You are talking both about units, and then you are talking about total costs. I cannot determine on those bullets whether or not how that changes bullet 5 relative to the unit costs. Do you see what I am saying?

MS. WILKINSON: Yes.

MS. SECUNDY: You do not have to answer that now.

MS. WILKINSON: Right.

MS. SECUNDY: I think it would be very helpful if you could continue the projections relative to unit.

MS. WILKINSON: Yes, we will do that. Thank you.

DR. CAPLAN: Last comment I will make, and then I will ask Dr. Williams to come up.

I think it would be helpful to us if after you begin the process of talking with Congress and so on, any information that you have that is in pie chart or tabular form or whatever about costs, what tests cost, what the component costs are to get to the unit to put some meat behind John's question about bargain, not bargain, what has gone up. That would be very helpful to have.

So, if you could get that and get it to Steve, I think we would be very interested in seeing that.

MS. WILKINSON: And I believe we could do that.

DR. McCURDY: Art, it is my impression, which may or may not be correct, that there is relatively little uniformity in how costing is accounted for in blood banking.

My question, I guess, is: Would it be possible for blood banks under the auspices of the AABB or whatever to get together and come up with a uniform approach to accounting for costs and the whole blood banking segment of this area? I think that might be very helpful in helping to understand the other issues.

DR. GUERRA: Art, if I could just ask, could you give us some indication within your association of how many the blood banks are operated as for-profit and how many are not-for-profit?

MS. WILKINSON: I do not know that there are any for-profit blood centers any longer. Everything is not-for-profit. Right, yes.

DR. CAPLAN: I am tempted to say, "And pretty darn good at it, too."

[Laughter.]

DR. CAPLAN: All right, thank you.

MS. WILKINSON: Thank you very much.

DR. CAPLAN: The floor is yours.

Having gone through the compensation price, we are going to hear next about incentives to encourage availability.

DR. WILLIAMS: Thanks.

Good afternoon. I have been asked to discuss the issue of incentives that are sometimes offered by blood collectors or sponsors to encourage blood donation.

Because time is short, I am not going to provide too much background or history on the issue. I have created a handout which was distributed to committee members, which gives both a reference list and a sort summary document.

I will start out with a definition. In the context of this talk, I am going to define "incentive" as anything provided by a blood center or sponsor that goes beyond the warm glow that one gets by helping a fellow human being. This goes to everything from a token recognition pin to cash provided to a fraternity or sorority or something of that nature.

I do want to mention two key events that really brought recent focus to the incentive issue. The first was a 1994 association bulletin issued by the AABB which provided the findings of an ad hoc donor incentive subcommittee.

This document identified and categorized commonly used incentives and advised members of the AABB of those incentives that may or may not be appropriate without creating any specific restrictions. It just made suggestions.

The second issue was an FDA-sponsored workshop in September of 1996 that reviewed the incentive subject, I think, with an eye toward alerting FDA about incentive practices that might compromise the high level of safety.

DR. CAPLAN: I do not mean to interrupt you, but he has got the mike amped up a little. So you should be able to stand back up.

[Laughter.]

DR. WILLIAMS: I think the purpose of the FDA's conference was to characterize incentive practices that might compromise the current high level of safety that the U.S. blood supply currently has.

I think it is fair to say that both the subcommittee report and the FDA workshop were hindered by a dearth of data in three specific areas surrounding incentives, and these are some areas I am going to try to address today with some preliminary data.

The first is: What is the prevalence of incentive use in blood centers toady?

The second is: What is the effectiveness of specific incentives to encourage blood donation?

Third, what is the extent to which incentive offerings may entice a donor to provide an inadequate medical history and inappropriately proceed with donation?

I am going to share with you some preliminary highlights from three different studies that have begun to address these issues. The first two studies are anonymous male surveys of active blood donors conducted by the NHLBI-sponsored REDS study. These were done in 1995 and 1998.

The third is a survey of blood center incentive practices and experiences conducted by the National Blood Data Resources Center in 1998.

I want to stress that the analyses of the 1998 data are preliminary and subject to change, particularly as data are further cleaned and weighted and subjected to multivariate analysis. So please keep that in mind.

In the 1998 survey, we added three blood centers to the core REDS group. You will see detailed methodology that we used for those surveys in Tabs C or D of the committee handout, which details our 1993 survey.

For 1998, we added the New York Blood Center, Life Blood in Memphis, and Blood Bank of San Bernadino to the group, for a total sample size of about 94,000 subjects.

In brief, the survey technique used--and this was the 1995 survey from which a lot of the data will be coming for the talk--the number of donors for a 2-month sample eligible to receive a survey was 144,000. We used an 8.3-percent random sample, which our sampling frame was 12,000. We had a 67.4-percent response rate, and of those, 62.2 percent were complete and used for the analysis.

The types of categories that we used were loosely based on the AABB subcommittee deliberations. There is the token category, pin, certificate, et cetera, with really minimal monetary value, and I have color-coated some of the slides. When you see blue, the is the token type of award.

The compensatory-type incentives, either cash provided to a sponsoring group, tickets to an event, discounts on merchandise, for example; the gift category, which I considered separately here, the typical mug/T-shirt offering to blood donors; and then a miscellaneous category which contains some of the interesting ones, extra time off, medical testing, blood credit programs, et cetera.

Now, the first issue I am going to tackle it the prevalence of incentives offered at the time of last donation. This is a specific questionnaire on the survey that says: At the time of your last donation, were you offered anything by the blood center or sponsor?

Here, I am comparing 1995 survey data with 1998 survey data, and the reason for this is there appear to be some fairly marked changes between those two periods.

In the gift category, those donors who reported receiving some sort of gift went from 9.7 percent up to 22.8 percent in 1998.

Overall in the compensatory category, it was 3.1 percent from 8.8 percent. I will not go through the breakdowns, but you can see most of them have a rise between the time period.

In the miscellaneous category, again, almost a two-fold rise, 15.7 percent up to 30.4 percent; medical testing, almost doubled. This is attributed in part to the fact that the auto-analyzers that now run ALT testing also conveniently run cholesterol tests. So blood centers are commonly offering supplemental cholesterol testing.

Sometimes sponsors offer extra time off from work as part of the donation process. This has always been kind of a controversial incentive, but this increased in prevalence in 1998 as well.

Then one area we did not measure in 1995, but we did in 1998, was provision of some sort of community or educational credit for a donation, and this was close to 1 percent in 1998.

So, looking at the summary totals, any incentive in 1995 versus 1998--I am sorry. That figure is missing there. I forget exactly what it is, but it looks like it is about 81 percent.

If you subtract out the token items which are really not the issue of our discussion, you are left with a net receipt of non-token incentives of 26.1 percent in 1995 and 62 percent in 1998, a big jump between that time period.

Again, it is preliminary. There are three extra centers involved. So some of that needs to be accounted for, but I think the trend is going to hold.

Moving onto a different consideration, what donors do incentives motivate, and can this be broken down by different subcategories of donors? Here, we offered a theoretical question. If you are offered any of the following for donating blood, what effect, if any, would it have on your decision to donate?

And we used a scale from "would strongly encourage" up to "would strongly discourage." We wanted to measure a discouragement factor because there has been at least some anecdotal observation that some donors are turned off by some of these activities, and we wanted to try to measure that.

For analysis, we used the 1 and 2 figures here as an encourage datapoint and 4 and 5 as a discourage datapoint, and then measure the net benefit.

What you see broken down here by individual incentive--and remember the color coating. These are the miscellaneous, and the green are the compensatory type. Our horizontal bar graph is showing the total encouragement effect of a particular incentive to the donors on a theoretical basis, and then the green is a discouragement factor. So we can see that donors react to a future blood credit very strongly with a relatively modest discouragement factor and a net of 58.6 percent encouragement.

Then, going down the line, I have these in sort of decreasing order. Medical testing, also strong encouragement factor, extra time, and tickets, about 25 percent net encouragement factor, but you gradually see the level of enthusiasm starting to back down and the level of discouragement starting to increase. By the time you get down the lottery in raffle tickets, you really are potentially turning off some donors by using that particular technique.

We also took the encourage data and looked at that in the context of donor demographics, again broken down by the same categories. There really were quite a few data here. So the only ones I showed were the ones that had P values of less than .001, i.e., highly significant associations.

You can see that your younger-aged donors really react pretty strongly to most of the incentives, with exception of blood credit, and male donors react fairly strong. Donors who were never married are interested in medical testing, and first-time donors, in particular, seem to be attracted by the compensatory-type incentives.

Finally, to look at any risk associations, this is our first effort to do this. We've defined a factor known as composite risk, and what that includes is a donor who had any positive screening test on the last donation, and we know that for survey respondents. We also know by responses within the survey who used the confidential exclusion mechanism on their last donation. We have a question about those donors who donated to seek an HIV test. And we have the concept of deferrable risk, which is detailed in that JAMA paper, which is the fourth element of that composite risk factor.

Comparing composite risk to the theoretical situation of how donors would react to an incentive, the only incentive that created a significant relationship to composite risk is a cash award. And the odds ratio for that was 1.56, with an odds ratio of 1.05 to 2.35. So just over the level of significance.

Some of the other controversial ones were not significant, had odds ratios that were very modestly elevated, but I think one needs to consider these data in the context of some other factors, ways you can break down donations. For instance, if you considered all male donors, they would have an odds ratio in this general magnitude. If you consider donors who seek HIV tests and use deferrable risk as a risk membership, the odds ratio is up as high as 4, and the same for Q using the deferrable risk.

So I think we're approaching a way that we can associate risk with incentive use. These are very preliminary, and we hope within the next six months or to use the large number of respondents we have in the '98 survey to produce some reliable data on what risk associations, if any, there are with the bulk of incentive practices and either exonerate or implicate some.

Next I'd like to spend a few slides looking through the survey from the NBDRC. We took a different tack with this one, and that is to survey blood centers on their perspectives of incentive use. Marian Sullivan, who presented this morning as part of this, as did Celso Bianco from ABC, and it was supported by a National Blood Foundation administrative grant.

The objectives that I'm going to address here are to assess the use, effectiveness, and oversight of blood donation incentives provided by both blood centers and sponsors and compare blood center observations with the blood donor observations from the REDS surveys.

Methods, this is a 10-page mail survey distributed in September of 1998 to all blood collection facilities in this country. This is a different survey instrument than the one that Marian detailed earlier, 152 blood collection facilities, and these data are linked, as it were, to the blood centers so that we can tie it into data points from the larger collection and utilization survey.

We had a 62 percent response rate from the blood centers, 50 percent from hospital collectors. We're only considering blood centers in the data I'll present today. And the data that came in represents about 67 percent of the whole 1997 U.S. blood collection.

Now, one element we wanted to capture is theorize that blood centers are not necessarily aware of all the incentives that might be offered by sponsors, for instance, at a worksite. The collecting agency might not know what the worksite is providing to their donors. So we asked the full range of incentive items and asked the blood centers whether they were aware of sponsors offering this particular incentive during 1997. We had a no category, a yes category, and a do not know category.

What I have summarized here is the do not know data because I think it's of some interest to know to what extent blood centers don't know what sponsors are offering.

In the miscellaneous range, a wide from 2 percent to 29 percent, the incentives a blood center didn't know if they were being used. Compensatory range, similar. In the gift range, they seemed to have a pretty good idea what was being given, and about 12 percent in the area of token item.

So I think this gives some of the first data regarding in a broad sense to what extent blood centers know what's being given by sponsors.

Of some interest, too, we asked the question what blood centers considered to be the incentives which were most attractive to school-age donors, i.e., high school- and college-age donors. And this is just some of the feedback we got. Tee shirts are a big item; 75.8 percent of the blood centers used them for that particular donor subset. Food was the next big item, big surprise there. Class credits, tickets, pizza parties, and mugs also made that top five list.

We wanted to get some data on the extent to which blood centers reviewed incentives that were proposed by sponsors, to what extent they documented them. Blood centers recorded the incentives provided by drive sponsors 76.3 percent of the time. They actually had a review process for incentives offered by sponsors 20.7 percent of the time. And they disallowed incentive offerings--29.4 percent indicated they had disallowed something during that year, and this is a list of some of the things that have been disallowed by blood centers as being inappropriate.

I think based on blood center responses, far and away most incentives are given to everyone who comes to donate blood. It's pretty well recognized that you don't reward only those who complete the process because that might stimulate an appropriate donation. Some incentives were given only to successful donations, but that was not the situation for the most part.

Finally, I wanted to introduce just the perspective on the blood center as to the proportion of blood collections where donors had received an incentive. Remember, from the donor perspective, it was up around 60 percent. From the building perspective, for sponsored fixed-site collections, the range of all of these is 0 to 100. The median is 5 percent; for fixed-site non-sponsored collections, 15 percent; and for temporary drives that are sponsored, 20 percent. And this excludes, you know, cookies, drinks, and token recognition items.

So there is a little bit of a disconnect that might be explainable in different ways between the blood center perspective of the role of incentives and what has actually been received from the donor perspective. I think there are multiple explanations for this, but it's something interesting to work out in the future.

So, some brief conclusions. Use of non-token incentives to encourage blood donations increased markedly between 1995 and 1998. Of the nine incentives studied, the highest net encouragement to overall blood donation behavior is provided by blood credit, medical testing, extra time off from work, and tickets to some sort of an event.

Encouragement to donate by incentives was related to a variety of respondent characteristics, most strongly to younger age, male sex, no previous marriage, and student status.

Incentive use appeared to be recorded by about three-quarters of blood centers. It's reviewed by about 21 percent of blood centers, and some sponsored incentive offerings are made without knowledge of the collecting blood center. And there is a range up to about 30 percent there.

Keep in mind there are some limitations to survey data. These are preliminary. They're reliable to the best of our ability, but there needs to be more analysis done with them.

Don't confuse the data analysis based on a theoretical situation of being encouraged by an incentive versus an analysis that would be based on a donor who actually received an incentive. We'll be doing the latter analysis in the course of the next few months and tying in the risk information to that. And I think that will be more meaningful.

Response rate to these surveys from first-time donors tends to be lower than the sampling frame, and any potential biases that might be introduced need to be considered.

There are active programs both within REDS and NBDRC to follow up these with some interventional studies and further work. I'm not going to detail it at this time. But there are further studies underway in both institutions.

Finally, I'd like to acknowledge the folks who have been most heavily involved in both of these surveys and, in particular, the staff at the blood centers and the respondents from the blood centers to the NBDRC survey.

Thank you.

DR. NIGHTINGALE: Thank you very much, Dr. Williams.

I believe the bell that you heard in the hallway was Dr. Caplan's cell phone, so I will hold the fort down for a few minutes.

[Laughter.]

DR. NIGHTINGALE: Do any members of the committee want to ask any questions of Dr. Williams? Dr. Gomperts?

DR. GOMPERTS: Dr. Williams, in addition to these specific incentives that you mentioned, have you considered other issues that could impact the frequency of donations and return? For example, the convenience issue, it takes time to actually donate blood, but it also takes a greater period of time to get to the center and so on and so forth. That's the one thing.

Secondly, the comfort issue, the capability of the technologist placing that pretty large needle, issues of feedback from the point of view of what's happened to that unit of blood, the altruism and the consequences, and also around that the potential certainly for hospital blood banks to perhaps use the directed donor situation around a particular drive.

And, finally, there is some soft data to suggest that individuals with pretty substantial red cell count, hemoglobin levels, may well derive a benefit from this point of view of increasing red cell count, hematocrit level, decreasing the potential for iron-associated autoxidation and arterial damage issues, and perhaps do more science around that one; in other words, indicate that there is an equal benefit in donating blood.

Have these been considered?

DR. WILLIAMS: We've tried to be pretty thorough with the survey, and we actually captured data on all of those except the feedback issue, because I wanted to stick with incentives on this talk.

I would also add, you know, the issue of HIV test seeking is also a potential important factor that brings in donors.

We do have data on most of those other issues, particularly with the '98 data. It really hasn't been looked at, but we've tried to structure the survey that we could get something meaningful in most of those issues, and I think you'll be seeing it over the next year.

DR. NIGHTINGALE: Dr. Busch?

DR. BUSCH: Alan, it was interesting to see blood credit such an important potential motivator. I'm a little unclear. Years ago, I remember Denise Hemphill, who was the founder of our center, was very pro-credits, and we had a system--and we were one of the last to phase out, I think, a system that literally for each donation gave a donor his own record or credit at the hospital where he got blood subsequently would get a discount on that unit. And in part because of, I think, the logistics of tracking all that, but in great part just the cost issues and the effort to reduce the cost of our operations, led us to phase that out and many other programs.

What are these--separate from that, whether there's a discrete credit with each donation, you know, when you give, you kind of are asked which group do you want this donation to be attributed to. But I'm not clear on--you know, a church or wherever you give. But I'm not clear whether that really translates into anything of value to that group. Are donors misunderstanding what credit--

DR. WILLIAMS: The wording on the question, I didn't bring the questionnaire up with me, but it's worded to the extent that blood credit for future blood needs for yourself or your family. I think it's targeted pretty clearly toward the sort of traditional sense of blood credit. We do get a prevalence on that. One of our participating blood centers does have something that could be interpreted as a blood credit program. But certainly there are some donors who think this is still in place in some blood centers that don't continue to have such programs.

DR. WILLIAMS: It's interesting, again. That may be a major motivator we're ignoring or have phased out because of improper interpretation of cost issues.

DR. NIGHTINGALE: I guess Dr. Gilcher and then Dr. Hoots and then Dr. Penner, if that's okay.

DR. GILCHER: My comments relate in part to what you just asked, Dr. Busch, and my comments are this, Alan: What we've tried to do at our blood center is to, what you're calling incentives, actually break them down into three categories: incentives, benefits, and recognition. And I want to focus on the recognition issue because there is the perception, when a group donates, that they're building a credit. But they use the credit, in fact, to receive recognition from the blood center. We spend significant dollars to host luncheons and so forth where we recognize groups, and obviously that's based upon the number of donations made by that group. We also recognize specific donors in the apheresis area at luncheons, and I think very clearly this is a significant cost when you put it into the system overall, and I'm not sure that that was measured.

In fact, my question really is: Has that been measured at all, the effect of the true recognition?

DR. WILLIAMS: The extent to which we measured recognition, the question was worded in terms of receiving a pin or certificate or something like a bumper sticker. We didn't mention sort of the recognition of dinner and that level of recognition.

I think if you remember from the bar graph, the recognition factor itself had a very low discouragement level, but also a relatively modest encouragement level in terms of some of the more type of thing that you can hold in terms of motivators.

DR. GILCHER: Exactly, at the personal level. But when we do that form of recognition for a group, what that really helps us do is to keep that group or encourage other member groups in the community--I'm talking about industry, hospitals, churches--to actually participate in the blood program. And we think that that recognition has been extremely successful in our area.

Again, I think most people know that we're one of the few areas that does not have shortages. But we have really focused very heavily on that type of recognition. So the group as an institution, I can say, is receiving credit, and that encourages them, the leadership of the group, the membership in that group, to be donors.

DR. WILLIAMS: One thing we tried to do I the '98 survey was bring in sites that had some sort of unique program. Oklahoma is already a participant, and we can look at those data specific to that center. We also tried to bring in Delaware, which has a membership type program that they're very excited about, but we weren't able to bring them in.

DR. NIGHTINGALE: Dr. Hoots, then Dr. Penner.

DR. HOOTS: I'm interested in--did you survey efforts to remove disincentives as well? For instance, I don't know how many adults are needle-phobic, but my guess is that there are a substantial number that are. And being a pediatric hematologist, we spend a lot of time with children trying to deal with their needle phobia, including using topical anesthetics to try to deal with that and encourage them and that sort of thing.

Has there been a concerted effort to do that, or has there been any pilot projects to do that to try to encourage people who say they would never donate because they're afraid of needles?

DR. WILLIAMS: Within this survey we didn't measure, again, that level of detail. We assessed how comfortable the donor was with the donation process, the technical skills of the phlebotomist, and the time they had to spend waiting.

I know of one large blood organization that's investigating the painless phlebotomy. There was some survey work done on a pilot basis, and clearly donors were very much in favor of something like that, yes.

DR. NIGHTINGALE: Dr. Penner?

DR. PENNER: One of the big issues in the State of Michigan was a change in the manufacturer's attitude with respect to allowing workers to leave their place of work and donate in the factory setting, which at one time earlier on was just allowed, and then suddenly the change of looking at costs for the manufacturer, they removed that incentive entirely. Then one had fewer and fewer of the unionized people coming down to donate.

Do you have any information on that?

DR. WILLIAMS: As far as policy changes related to offering extra time off of work?

DR. PENNER: Yes. Did you pick up the differences as a result of that?

DR. WILLIAMS: We probably could--well, I don't know. We're not collecting it at the sponsor level. We have a lot of questions related to time off from work and extra time off from work, because that was one of the targets that we wanted to meet. So we can distinguish time off from donation versus extra time as a reward for donation.

Whether we can get any trend information out of that due to policy changes, I think it would probably be difficult because we only characterize the collection site as being fixed versus temporary and church, school, that sort of level. It seems like you might need to get to a specific sponsor to be able to collect that.

DR. NIGHTINGALE: Are there any other questions from the panel? Dr. Davey?

DR. DAVEY: Just following up on Dr. Hoots' comment, we are very interested in that very issue about making the donation experience as pleasant as possible, and actually there is a technology you may be familiar with called Numby, where we use an apheresis technology to actually infiltrate the skin above the venipuncture site with xylocaine, and it works very nicely. It is a painless phlebotomy. And there are some other technologies along that line also.

Actually, I think a survey that was done recently, the number one reason why first-time donors don't come back is they've had a negative experience. It hasn't been pleasant. Either the phlebotomist hasn't been friendly to them; the stick has hurt; the environment was not pleasant.

In any event, I think enhancing the donation experience just along those lines is very important, a very good point.

DR. NIGHTINGALE: Dr. Piliavin?

DR. PILIAVIN: I've ben sitting here not saying anything for quite a while, but what you just said triggered something in me.

One of the problems with asking people questions about why they did do something, why they didn't do something, why they might do something, is that people have very, very little insight into what actually makes them do things, which, of course, one can sometimes turn to one's own uses.

But in regard to what you just said, I have longitudinal data which does not depend upon what people actually think was why they didn't come back, and one of the strongest predictors of first-time donors not coming back--and, in fact, a mild predictor of later donors not coming back--is their reports at the time of that donation of even bad social experiences, certainly pain, anxiety that was not relieved, having a reaction, being deferred. All of these things that make them feel like it's not a friendly, pleasant place to be, either physically or psychologically, definitely depresses the rate of return.

DR. NIGHTINGALE: There are other questions that I would, on behalf of Dr. Caplan, ask the Caplanesque question of Dr. Williams, and Dr. Piliavin may wish to comment on this as well. I think you can see from both the quality and the quantity of the questions that you've been asked the interest and the importance that the committee apparently attaches to your research, and certainly I believe we all do.

Is support for your research adequate or would you have any serious comments about what might be done to facilitate progress of research of this sort that we obviously take to be so important?

DR. WILLIAMS: I'd have to say that the National Heart, Lung, and Blood Institute through the REDS study has been extremely supportive of all our endeavors in this area. In fact, if there's a problem, it's trying to keep up with the projects that we've committed to do. Funding is not an issue in these areas. But there's also a message that, you know, multi-center capabilities like REDS are really the way to go for some of these issues in the future, long-term type studies.

DR. NIGHTINGALE: Dr. Williams, thank you very much.

Dr. Busch is our next speaker, and Dr. Busch will talk about demographic correlates.

DR. BUSCH: I broadened my topic a little bit to term my title "Categorization of Donors," but I'm a little bit beyond subcategorizing our donors beyond just demographic correlates, to give you the broader perspective of how we can really sort our donors into many different subgroups and ask questions about relative safety of donors defined by different categorizations. And it's important to, I think, view the broad context of categorization so that we don't get focused on an individual subgroup sort and make decisions without recognizing how many different options there might be to do that, and the broad ramifications that assort based on one criteria may have with respect to other agents or other categorizations, the sort of fall-out of individual focused decisions.

I want to just give an overview of these kinds of sorts and then present some illustrations of what I think on the surface look like reasonable strategies or policy changes based on a single sort, in fact, I think have had adverse or could have adverse consequences to overall blood safety and availability.

I should up front acknowledge this is a REDS-related analysis, and in particular, Simone Guinn and George Schreiber from REDS were instrumental in compiling the data I'll be sharing.

In terms of sorting the donor base, I'd kind of define three different types of variables: donation-related variables, demographic variables, and--I'll get to it in a minute. I can't even remember the third grouping.

With respect to donation variables, the type of donations, the allogeneic versus autologous, and within the allogeneic group, community-directed apheresis. And the REDS group has looked at many of these over time, and in general, actually, with respect to safety, our data has demonstrated very little difference in the safety of volunteer community donors versus directed versus regular apheresis donors.

Autologous donors, because they don't go through the full questionnaire because most centers don't allow cross-over, do have higher marker rates and higher risk, but that's because, in fact, they're allowed to and allowed to give repeatedly even with risk.

In terms of frequency, I'll address a little bit of data, the little bit that we have comparing first-time versus repeat donors. You heard earlier from George Schreiber who presented data on the rate of donations and the patterns of donations among repeat donors, that, in fact, surprised us in showing that there really doesn't appear to be evidence to support the premise that more frequent donors or that regular apheresis donors have a lower incidence for the known agents. And as I think you'll see, I think our presumption that first-time donors are probably much higher risk than repeat donors is in part, I think, a misunderstanding of the difference between prevalence and incidence, and if we can focus on incidence alone, we actually see that first-time donors are only slightly higher risk than repeat donors.

We can also sort our donor base based on the site of the collections in terms of region of the country, fixed versus mobile site collections, different types of mobiles, for example, you know, high schools, churches, et cetera. We can look at risks associated with those kinds of collection patterns.

Also one that we want to look at, we haven't yet done, but an urban versus rural definition, donations given in zip codes associated with, you know, inner city or suburban or rural, and comparing incidence in those kinds of sorts.

Alan just addressed the issue of incentives.

In terms of demographics, we routinely collect a number of characteristics about donors, and then we can look at prevalence and incidence across these parameters: gender, age, race, ethnicity, level of education, country of birth, where these individuals live. I'll present a fair bit of data, and most of the presentation will focus on these kinds of sorts.

You can also then--from the interview of the donor, we have many questions that lead us to potentially defer or be concerned about a higher risk associated with certain donors. We have malarial area travel deferrals, Sub-Saharan African deferrals are back in place until we completely fix Group O sensitivity, and all of the current debate over deferring donors who have been to Great Britain.

Medical histories. There's quite an interest in transfusions. I'll show a little bit of data there. The French have actually, I believe, instituted a policy where previously transfused individuals are no longer allowed to give blood, and I'll show you that in the U.S. about 78 percent of all blood is given by people who have been transfused in the past, and, in fact, as I'll show you, in general, not only did they have no higher an incidence, they even tend to have a lower incidence because they're older individuals. They have higher prevalence in first-time, but a good example I'll show of where prevalence and incidence are a disconnect.

A history of hepatitis. I think, you know, several years ago FDA proposed relaxing or eliminating that historical question, and I think for inappropriate reasons the blood centers were resistant at that point. I think this question no longer serves any purpose in the context of current screening tests.

Behavioral histories. These are obviously key issues. Some that we haven't focused on: number of heterosexual contacts are currently not a basis for deferral. And then some old tests that serve as sort of surrogate markers for specific risks.

So all these different sorts of the donor base allow one to look either in isolation or in combination at potential options for policy changes.

This is a slide from a different talk, but I threw it is because it introduces the importance of making distinctions between incidence and prevalence, and also the factors that influence incidence and prevalence among people giving blood.

In general, what--historically, people have tended to just look at overall prevalence rates per donation. And it's only in the last five to ten years that the REDS group, for example, has really sorted data effectively into looking at prevalence rates among first-time donors versus incidence rates among repeat donors. And, importantly, the prevalence in our first-time donors and, to a lesser extent, incidence in repeat donors really reflect both the combined effect of the general population prevalence of these agents and the effectiveness of the donor historical questionnaire and deferral criteria on eliminating prevalent infections.

But that prevalence does not necessarily have a direct impact on risk. The real driver of risk we know is from the window phase units, which are people giving during that seroconversion window, and that's best compared among groups by focusing on the incidence rates, the rates of new seroconversions in your donor pool.

Now, the problem is that in general we can't measure incidence in our first-time donors because they're not seen over time. But I'll show you one bit of data that has allowed us to get at incidence in first-time donors.

This slide just puts side by side the prevalence per 100,000 first-time donations versus the incidence per 100,000 person-year among repeat donors. In this last column, I've just expressed the prevalence-to-incidence ratio which gives you a sense of how much more frequent infections are in first-time donors compared to observed seroconversions in repeat donors.

In essence, what prevalence really represents for these markers, which for the most part persist through life, is a lifetime accrued incidence, the probability that that person became infected anytime in their lives; whereas, incidence reflects the rate of new infections, observed seroconversions. And you can see that the frequency of infections among the first-time donors is much, much higher than among repeat donors, ranging from about seven-fold higher for HIV to 170-fold higher for hepatitis C. So for hepatitis C, for example, it's a very prevalent virus, probably close to 2 percent of the population is infected, a half a percent of all first-time blood donors are seropositive. But the rate of new infections in the donor pool is actually quite low.

So, in some respects, the prevalence misrepresents the incidence because you can see dramatic differences in the prevalence rates of these agents; whereas, the incidence rates are really quite comparable and really exceedingly low, particularly compared to background incidence.

Now, one issue I want to just quickly address is that issue of first time versus repeat donors. Again, the incidence rates I just showed were incidence rates in repeat donors who were seen and giving over time, and we can quantify how much time these people are followed, and then the rates of seroconversions and express an incidence rate.

We've never until very recently been able to measure incidence in individuals who are just giving a single sample, a cross-sectional population, which is really what our first-time donors represent. But recently there's been some strategies for HIV and I think a similar strategy will be available soon for hepatitis C that allow us to detect recently infected people at the time of a single blood specimen, and by understanding window periods, we can then estimate the incidence of infection in that sample set, in that population.

For HIV, a study, a collaborative study with CDC, particularly Bob Jensen, led to development of what we call a detuned or a less sensitive HIV antibody test, which allows us to take samples that are found to be antibody positive and basically run those samples on this less sensitive assay which is designed to detect--basically the samples are run at a very high dilution and with reduced incubation periods. And the assay specifically delays the detection of seroconversion by 129 days, or about four months. And by taking seropositive samples from first-time donors and testing them on this less sensitive test, we can identify the recently infected donors subgroup, and then by some simple calculations, we can estimate the incidence rate.

Indeed, that's what we've done in collaboration with the Red Cross. About 860,000 first-time donations over a three- or four-year period were screened by routine methods; 131 were found to be confirmed infected, and of those, 18 were in that early seroconversion window that resulted in their being negative by this less sensitive assay.

By simply calculating out an adjustment by multiplying by 365 over--this should be 129, we can then adjust up to annualize that and get an incidence rate, which in this analysis gave us an incidence of 5.9 per 100,000 person-years. And we can now use this incidence to compare with the incidence in repeat donors, and if you just focus over here, we can see that the incidence in first-time donors was estimated at about six, and using either a classic or a similar detuned strategy to measure incidence in repeat donors, it came out at about 2.9. So, really, only a two-fold difference in the incidence between first-time and repeat donors.

Of course, because first-time donors contribute only about 20 percent of the blood, we can also estimate a composite incidence by weighting these, and that came out at about 3.5. So the contribution of first-time donors to overall risk is fairly modest because they contribute--yes, they're slightly higher risk, but they contribute a relatively small proportion of the blood.

Now, this estimate that we derived of relative incidence in first-time versus repeat donors of two is quite similar to some earlier estimates, one published by Cumming, et al., and Roger Dodd, and further used in the Lackritz New England Journal paper, that estimated prevalence--when testing was first begin for HIV, the prevalence in first-time donors was 1.8 times that in repeat donors. And Alan Williams in his JAMA paper looked at the rate of deferrable risks in first-time versus repeat donors, and it came out 1.6-fold higher than repeat donors.

So all of these numbers are really quite consistent, indicating that first time donors may be slightly higher risk, but only about two-fold, much less than many people predicted, thinking that first-time donors were probably much higher risk. They do have a much higher prevalence, but that's because it's prevalence from lifetime exposure. Their underlying rates of new infections are only slightly higher, and then once you're into the regular donor pool, we could not detect any difference in risk associated with frequency of subsequent donations.

I just want to give a few illustrations of how prevalence rates, comparisons of prevalence rates can fool you and you can make sort of policy suggestions or recommendations that, in fact, then when you focus on incidence, which is the true measure of risk, are not justified.

For example, in a paper published also in JAMA by Alan Williams and the REDS group on HCV, the prevalence of HCV when categorized by race/ethnicity was significantly higher in blacks and Hispanics than in white donors. That might be a concern; this is mostly driven, though, by prevalence in first-time donors. And when we look at incidence of HCV by race/ethnicity, we actually see that black and Hispanic incidence is no different than white incidence. So, in other words, the prevalence data which would have suggested perhaps a race/ethnicity correlate of risk, in fact, is not borne out when we look at new transmissions in the donor pool where the incidence rates are comparable.

Another example of that is with respect to hepatitis B, where here we're looking at prevalence and incidence side by side for hepatitis B by race/ethnicity. What I want to emphasize is the prevalence of hepatitis B is much, much higher in persons of Asian descent, particularly persons who have come from or were born in countries where hepatitis B is endemic. But in contrast, when we ask the incidence question, there's really no difference between the incidence of hepatitis B in Asians than in Caucasians, and most of this high prevalence is associated with perinatal transmission of hepatitis B. It has nothing to--the Asians are not at any higher risk of continued exposure and acquisition of hepatitis B in adult life in this country in the donor pool.

A third example, I think, of where prevalence can fool us is the history of transfusion I alluded to earlier. Again, in Alan Williams' paper on hepatitis C, he demonstrated that previously transfused individuals had a significantly higher prevalence of HCV than did non-transfused individuals. And we've seen the same thing with HTLV and hepatitis B.

There is no question that individuals transfused prior to screening were at higher risk and did acquire these agents in their earlier years. In contrast--and this is the one overhead I wanted to show. This is the latest data. If we look at the incidence by blood transfusion, you basically can see that for each virus--HIV, HTLV, HBV, and HCV--that the incidence is identical in the persons who were or weren't transfused, essentially statistically identical.

Interestingly, for many of the viruses, the incidence is actually lower in the individuals who were transfused, probably reflecting the fact that these are generally older individuals who have lower rates of exposure in their older age groups. So, again, an example of where prevalence would have suggest that a policy of deferral of transfused people may be warranted, but when we look at incidence, that's not justified.

Another issue that's been discussed or alluded to is regional risk, and, indeed, both in the overall Red Cross data set and here specifically in the REDS data set, where we had five blood centers, we can look at incidence for each virus by region as a measure of risk, and we can see that for some agents there are regions that do have higher incidence rates.

For example, for HIV Centers, one in four have higher incidence rates. There are other examples where a center that might have a generally low incidence rate--for example, Center 5 here has a low incidence for most of the agents, but for hepatitis C they're in the high end. So the point here is that many of these sorts that might be reasonable or suggested associated with one agent may not be valid and bear out as a safer set for other regions.

In fact, in HIV we have done some further analyses using data from this less sensitive EIA test, and, in fact, region of the country drops out as a significant predictor of incidence when you factor in level of education and race/ethnicity. So region does not necessarily in and of itself, obviously, reflect a risk. It reflects the demographics and risk behaviors of the underlying population.

Another thing that can fool you is you talk about a region and you assume that it's a tight distribution of donors in terms of where they live or where they come from. I'll just show you a few slides to illustrate that when we talk about our regions, they appear to be quite tight. If you restrict the analysis--these are dots around the donations given to the Detroit Region Red Cross, but these dots are restricted to regions or zip codes from which there are at least 100 donations. But if we broaden that analysis and include individuals across the board in any zip code, you can see that people who are giving blood predominantly in the--giving blood exclusively in this vicinity, in fact, the zip code of residence ranges all over the place with many people in many of the urban regions throughout the country, particularly in the Northeast.

Similarly, for L.A., if you restrict it to 100 units, everybody's--all the zip codes are pretty much clustered in the L.A. region. But if you generalize it, you again have a large distribution throughout the country. We have a very mobile society. Perhaps the most extreme is actually Oklahoma, where, again, if you require 100 donations, it's all clustered in mostly western Oklahoma. But if you look at zip codes from which any donors who gave to OBI resided, they're all over the country, again, probably reflective of a fairly substantial military training program or bases in the Oklahoma region.

So just the emphasis here that when you talk about center or region, this is not necessarily as simple as it might seem on the surface.

A few other cuts, just to give you, again, a sense of how these things are much more complex and suggestions for one virus may not be true for another. If we look at incidence by gender, females are actually much higher risk for HTLV, and we think from other studies that many of these acquisitions are really related to heterosexual transmission from spouses or partners who have injection drug use histories; whereas, hepatitis B is much, much more common in male donors. So it offsets there, if you were biased towards one, you'd actually increase the risk for another.

Age-related incidence is interesting in that there's a sort of broad message that younger donors tend to have higher incidence rates than older donors, with incidence rates dropping over time. The one exception here that's kind of interesting and we really don't understand is hepatitis B, where the incidence of hepatitis B is much, much higher in this very young age group. Actually, the general observation really is that the very youngest donors have lower incidence, and then as you get into middle-aged groups, you run the higher incidence, and then it drops in the older age groups.

Now, this issue actually was of interest a few years ago and is a useful illustration of a policy, a sort of knee-jerk policy that can somewhat backfire. There was a lot of debate three or four years ago around CJD when the issues first came forward, and it wasn't clear, the distinction between new variant and classic CJD, and the FDA imposed a withdrawal policy that said that if a classic CJD case was presented, that you would have to withdraw--was identified, you would have to withdraw prior products from any of those donors and recall all the derivatives.

This led to a consideration in the source plasma industry of a policy of not collecting blood from older donors that was then further extended into some of the whole blood sector. And we were concerned that actually this theoretical benefit of excluding older donors to not observe cases of CJD and, therefore, not trigger recalls would have an offset in that older donors are actually lower-risk donors. There's less infections. And this is documented in a paper that we published, and all of these slides and this paper actually have been given to Mac and will be distributed to the committee.

But what you can see here is that for all of the viruses, donors who were less than 50 years old have higher incidence than do the elderly donors. And, in general, it ranges from two- to ten-fold higher incidence and, therefore, higher risk in younger donors compared to older donors. And if you model this forward and say what if we were to defer all older donors, what would happen--this is busy here, but the bottom line is that the net effect on overall risk would be an increased risk of up to 7 percent for some agents if we were to exclusively defer older donors because they'd need to be replaced by donors of a younger group. This doesn't even factor in the issues around getting those donors in in the first place, the replacement donors, or issues around risk associated with first-time donors. This is just the incidence in younger donors, repeat donors, is higher such that the net effect would be a significant increase in overall risk.

Another parameter that we could look at and we have begun to look at is education. And in terms of education, for each of the viruses--HIV, HTLV, HBV, and HCV--we have looked at donors and just grouped them into donors who have a high school or less education, donors who have some college, and donors who have college-plus, potentially additional education.

Among the donors who have only a high school education, we've tried to discriminate those who are actually still high school students versus those who should have completed high school but basically did not complete or have no further education. And that allows us to then sort of discriminate the younger high school students from individuals who simply didn't complete or go beyond high school. And what you can see in general is that, again, the persons who are still in school, very young individuals still in high school, are very low incidence generally. And then the peak risk usually is in the persons who have only lower education, a marker of socioeconomic status, probably, with declining risk. So, again, the lowest risks generally are seen in the better educated donors, in fact, across the board.

Here, again, hepatitis B is kind of interesting because we see a high rate of transmission in younger high school students of hepatitis B. This is of interest because the issue of deferral of British donors--I think there's data that suggests, and I think Alan Williams has presented this at the TSE meeting, that the British donors, persons who have traveled to Britain are predominantly older, college-plus educated, and generally Caucasian individuals, such that there could be an offset of risk by deferring those individuals. We would have to shift the donor base down to a broader mix of lower-educated younger individuals that could have a consequent effect on risk of other agents.

So, just to summarize, what I've tried to do is to paint a backdrop that emphasizes that there are many, many donation demographic, historical, and surrogate test variables that one can associate with viral infections. These parameters can be correlated with either prevalence or incidence, but they're often disconnected both between the viruses and often incidence--in other words, prevalence may be higher and incidence actually not higher, depending on the different agent.

The associations between different demographics and incidence differ for different agents, so some policy change that might seem appropriate for HIV may actually have a much bigger detrimental effect with respect to hepatitis C. So we have to be very careful and look at the overall balance of these effects.

Then, finally, it's important to recognize that all of these associations are really surrogates for underlying behavioral risk factors that really are responsible for exposure to these agents, and it's that issue that's both difficult to measure and that leads us to conclude that any recommendation for a policy change based on these surrogate variables is going to have very poor specificity and sensitivity.

Thank you.

DR. CAPLAN: Thanks, Mike.

Let's open the floor for questions. Jim?

DR. AuBUCHON: If I could just offer a very brief summary and then a comment. The summary is there's no such thing as a free lunch.

The comment is that, although it's clear, as you point out, Mike, that what we're really looking for are the behavioral risk factors, identifying those individuals who have engaged in some behavior that has placed them at higher risk for exposure to an infectious disease, we really have very little data on the suitability of different questions or the ability of different ways of asking the same question to determine the risk patterns of a potential door.

There were a few studies about a decade ago looking at how to ask questions. Obviously we have learned a lot about how to ask questions because of the decreased incidence and prevalence in our donor population as opposed to the general population. But yet we still know very little about exactly how to elicit risk behavior information from a donor.

DR. BUSCH: I agree. There is a survey that REDS has done, but I haven't seen the analysis, that asked donors, you know, how well they understand many of the questions that we ask them in terms of comprehension. And it's very disappointing that many of the things we're asking, the donors simply really don't understand when you survey them afterwards in terms of bases for deferral.

The other thing we don't capture, and actually Marian Sullivan's data indicated how many donations are lost through the test positivity, But what we're not capturing and have never studied are how many donors are deferred due to either--not coming into a blood center or, more specifically, due to the various questions that we're asking. How many people simply are coming in, reading the information or going through a history and deciding to not give? And no one has done studies to actually collect samples from these people and ascertain really the predictive value of any of the history questions we're asking. We just seem to be adding more and more questions--you know, more and more difficult to understand questions, without prospectively or retrospectively measuring their effectiveness.

DR. HOOTS: This is really fascinating, and I applaud all the work that's been done. It seems to me that it gets even potentially more complex if you're talking about the next great unknown pathogen. When you are on the upswing of the incidence slope, is there a way to model before you've really defined the incidence very well? I'm thinking back with HIV and with the whole Haitian issue, you know, were they at higher risk or not, and it created a lot of political furor.

But if you don't have a very good specific test, but you have some test, like let's just say if we get a test for a new variant or something, that you can take new cases per demographic group and take that test, and try to get some sort of estimate--again, I know I'm talking hypothetical--of where you are on the upswing before you get to a plateau rate where incidence can be clearly defined, so that the next time we have to deal--hopefully we won't, but we probably will--with the next pathogen that we can avoid some of the pitfalls of the politics and go straight to the science, which you so eruditely--

DR. BUSCH: That's a very good question. It's kind of the million-dollar question that we always are facing with a new agent risk.

I think on the positive side, I think the great powerful development over the last few decades has been the establishment of these very large, well-characterized repositories of samples from donors or recipients historically, because we can then quickly go back and test samples from 20 or 30 years ago and determine whether this agent is really increasing in prevalence, do we have an epidemic, or is this just a longstanding agent that, yes, may be there but probably isn't causing a lot of disease, look directly at transmission rates, maybe even define--identify infected cohorts from 20 years ago that we can ask the question of disease penetrants over time, so we can quickly investigate those things.

But those questions do depend on having accurate tests. The best example of what you're alluding to is, unfortunately, a dismal experience with the hepatitis B core antibody. During the early '80s, there was strong sentiment by some individuals that that test should be implemented as a donor screening measure prior to HIV. And the exact study that you're alluding to was done both in New York and in San Francisco, where donors who either gave in specific demographic risk groups or who came--for example, who designated their blood for research use only, which were often gay men in certain of these cities, the rates of hepatitis B core antibody were compared in, for example, the Castro district in San Francisco versus Marin, and there was no difference.

So this led to conclusions at the time that this test cannot discriminate these groups. But in truth, with hindsight, we now recognize that the anti-core test would have prevented 30 to 50 percent of HIV transmissions. So these surrogate tests and demographic correlates are very crude and very insensitive, and I think both we can't learn from them nor should we be in any rapid fashion making policy recommendations around them.

DR. CAPLAN: Mike, I have a question for you about the categories, the demographic categories themselves. We all know that for a lot of categories that we use, black, white, and so on, there is some--variation within these subpopulations is pretty large. Do you think it makes any sense not to use these markers in these particular categories to try and develop deferral policies? What's your thought about future genetic analysis, genotyping, that might give us better cuts on who is at risk or who is susceptible or who has a higher infection rate?

DR. BUSCH: That's interesting, because in our repositories--and we're building a new one now--we are explicitly prevented from intending--we have to, you know, in terms of donor consent, we have to explicitly indicate we will not do any genetic markers like that.

You know, I think there's two issues. One is the fundamental issue of true susceptibility to an infection, you know, where there are indeed certain genetic characteristics, receptors that are deleted in certain populations, but those are not absolute and are very rare. And I think that's kind of theoretical potential, but it has very little practical utility because even among populations in whom that resistance mutation may exist, it's a rare phenomenon.

In terms of other markers, really, again, that might be more accurate in terms of genetic history, that's really totally disconnected from behavioral issues. So what we're really dealing with in terms of these agents, both the known and most of the unknown, are behavioral or geographic exposures and not genetic-based exposures.

DR. CAPLAN: Okay. Thanks.

Ron? We asked Ron to talk some about increasing donation per donor, I guess is the way to put it, yield.

DR. GILCHER: Thank you for the opportunity to talk with you about technologies, and I was also asked to add a little information about costs, so you'll notice that the agenda doesn't say that, but technologies and their costs needed to increase recovery of donated blood products. And, really, what this comes down to then is looking at the automation that is currently available.

What I'm going to do--and I'm giving you a handout of all of the hard-copy slides, except for the pictures, that I'm going to discuss with you today.

For some reason, the projector is not--there it goes.

My focus will really be on a discussion of apheresis technology, which really allows flexible collection strategies, but what we've heard this morning and early this afternoon is that clearly our donor base is shrinking, our transfusion component requirements, if not staying the same, are, in fact, slightly increasing, and there are other ways that we could approach this: clearly, changing donor requirements to increase numbers of donors, increasing frequency of donations, and I'm going to focus increasing products or yields per donation, decreasing deferrals, and certainly within the blood center we have to obviously focus on getting updates done and reducing what are called incomplete draws. That is where a needle goes into the donor but we don't achieve the desired product.

What we consider as a basic requirement is that this technology, whatever it is that we're going to use, adds no risks to the donor, and obviously that there is no decrease in safety by the use of this technology to the recipients. In fact, there should be an increase in safety to the recipients and actually a decrease in risk to the donors. And what I will point out just very quickly, without saying it again later, is that using automated collection technology, one of the risks to donors that can be obviated is that fluids can be given back during the collection, so that the risks of hypovolemic or what I also call a relative hypovolemic reaction--that is, the donor who donates in the cool blood center, walks outside into the hot sun, vasodilates and falls to their knees--those types of reactions can essentially be eliminated by using this type of technology.

Now, I don't know how well you can see this in the back, but what I have done here is to outline the current available apheresis equipment in alphabetical order so that there will be no conflict.

The Baxter Corporation currently has three devices, and I'm going to show pictures of almost all of these devices, because when you see the pictures, they're worth a thousand words in terms of understanding their size, whether they're mobile, because as I show you the data from the Oklahoma Blood Institute, you will realize that in Oklahoma we rely very heavily on mobile-type operations as opposed to fixed-type operations. And I'll show you that data in a moment.

But the CS3000 of the Baxter Corporation is an older machine, a good machine, big, heavy, has essentially been replaced by a new machine called the Amicus (ph). It's very fast, one or two arm, and all of the platelets which it produces are leukocyte reduced. There is also a device called the Autopheresis C, which is a plasma-only collection device, and that is routinely used by many of the source plasma collection facilities in the United States as well as by some blood centers to do plasma-only collections.

The Cobe (ph) Corporation has now two devices: the Spectra, which is their older device, and essentially all of the platelets collected by that device are leuko-reduced. It's a one- or two-arm procedure machine. It's big, it's heavy, it's not transportable. The new device called the Trema (ph) really is one of the latest collection devices to become available and allows more flexible collection, in fact, allowing both platelets and red cells to be collected at one sitting.

Frezanius (ph), a relatively smaller company in terms of U.S. market share, has a device called the AS104, which has been used for therapeutics but recently in the last year was licensed for platelet collection as well.

And then the Humanetics Corporation, which essentially has three devices that all look very similar, but they are, in fact, separate devices: one for collection of platelets called the LM9000. It's the older of the machines; it's mobile. It can be one or two arms. There is the newer device--again, I'll show you pictures--called the 8150 that can collect red cells and plasma or, in fact, a double red cell. And then there is the PCS-2, which is an older device, so to speak, which is plasma only and, again, used by many of the source plasma collection centers throughout the world as well as some blood centers, such as our own center. And we essentially use virtually all of the devices that I'll show you pictures of at this point.

This device is the newer Baxter called the Amicus. Again, you can get an idea of the size of this device and in terms of its mobility.

This is the Autopheresis C. It's a plasma collection device by Baxter, and it's probably a little bit more of a mobile-type device.

Here you see the Cobe Spectra, a large device, not easily mobile.

Here you see their new machine called the Trema, and obviously a smaller device, which would be more mobile.

Here you see Humanetics machines that have the broad category called an MCS, mobile collection system, and they are smaller machines and are more easily transportable, this one being the LM9000 for platelet collections, this one being the 8150 for actually red cell collections. And, in fact, this donor is doing a double red cell donation.

And this is a plasma collection machine, the PCS, and the reason for showing this one is I want you to see the age of this donor. One of the things that we have found is that our young people really do like the new technology. They just grasp this, and they want to be on these machines. And this was actually one of our first mobile collections done at one of our high schools.

Now, I put this slide in to serve as a baseline, and I think this is important because most blood centers in the United States have now switched to a 500 ml collection, and that is into a 70 ml 3 percent anticoagulate, which essentially produces approximately the amount of blood products that you see here, about 350 mls of red cells in an additive solution with approximately 200 mls of absolute red cell mass.

In addition, about 250 mls of fresh frozen plasma, or if not used as that, it can be used as recovered plasma fresh frozen and then go into ultimately a source for plasma derivative production. That plasma contains 80 percent absolute plasma; 20 percent represents the anticoagulate.

Then if platelets are made, about 60 mls of platelet concentrate, which will contain about 0.6 to 0.9 times 10¹¹ platelets, pre-leukocyte reduction, because, remember, these platelets are not leuko-reduced, which is one of the clear-cut features of the automated collection technology. And if one subjects these to filtration technology, you will lose about 10 percent of the platelets.

Now, the next two slides show you techniques for essentially increasing yields, that is, using apheresis technology. With platelets, what we are doing with the newer equipment is clearly moving toward the double yield of what we define as a full dose, and at our blood center we are defining standards for blood products, specifically platelets and plasma within our medical community. And we define a full dose platelet as greater than or equal three times 10¹¹ platelets post-leukocyte reduction, because it is the only way that we produce platelets.

Currently, I believe that the FDA uses 3.0, but that is pre-leukocyte reduction. We are defining this post-leukocyte reduction. This is dependent on the technology used and the pre-donation platelet count of the donor. Clearly, the older apheresis technology is less apt to collect a double product; whereas, the new technology not only can collect double products, but using patented machine technology is capable of producing a leukocyte-reduced product.

Filtration can be used online, and so the end result is the same in terms of the leukocyte reduction capability.

One thing that we have added at our blood center is when we have products that don't quite reach two full doses, and that is to create something that we call a partial dose. And my light laser pen here is kind of worn out, so I'll just--if you see point 2 there, that is, one product of at least three times 10¹¹ or greater platelets post-leukocyte reduction and one product that doesn't meet--thank you, got it--and one dose that doesn't meet the criteria for a full dose, that is, in our center it's between 1.5 and 2.9 times 10¹¹ platelets in the product post-leukocyte reduction. And we're counting 100 percent of the products for yield and 100 percent of the products with low cell concentration counting.

So this has added a new platelet product in our system, that is, the partial dose, which is being utilized, for example, at our Children's Hospital since they really don't need full-dose single-donor platelets for many of the smaller patients. And also for the adult patients where they would have used two products, they are using one full dose and say one partial.

There is also a potential then with the Trema device that I showed you to collet platelets and red cells, one full dose of platelets and one full dose of red cells. The possibility for platelets and plasma, again, can be done with this equipment.

Double red cells, this is an interesting type of procedure because here the donor donates two full red cell mass equivalents, but the total volume donated essentially is almost the same as one unit of whole blood, collecting 180 to 200 mls of red cell mass per unit. Theoretically, this combination with a leuko-reduction filter could be a lower-cost option. That does not currently exist, but presumably it will in the near future.

The combination of red cell plus plasma, one unit of red cells and 450 to 500 mls of plasma--that is a true full transfusion dose for the plasma--or even double plasma, where we can collect three times 250 or one 500 and one 250, and this is how we package this for our hospitals.

We also make sub-products which are derived from the apheresis products, one called apheresis cryoprecipitate and cryo-depleted plasma. The cryoprecipitate is equivalent to three of the whole blood-derived cryoprecipitates.

Now, what I want to show you is the OBI data for 1998, and you'll notice that the first line is whole blood, and I put parenthesis red cells because that is what drives the system and that is the reason why whole blood is collected.

Notice the total number in our system of 130,000 total procedures, but look at the breakdown: 83 percent of those collections on mobile operations and 17 percent at fixed sites.

Now, if you look at all the rest on this list, which I'll go through quickly, note the percentage that were collected at fixed sites. It's essentially the reverse. And whether that's our fault or not, it is the way it is. We are trying to change that because currently the apheresis or automated collections are for the most part at fixed sites. And if you remember what the equipment looked like, you then understand how difficult it can be to move that equipment to mobile operations. In addition, as I'll point out in a moment, when you look at the various costs involved in the collection--and I include in that the donor time, needle-in, needle-out times are much longer--that impacts the people who will, in fact, do these kinds of donations.

But you'll again notice in our system one single plasma collection, 6,800, 83 percent at fixed sites; double plasmas, 525, 89 percent at fixed sites. A combination of red cells and plasma, this one we're doing a lot of, we're increasing that, obviously red cell-driven, 13,000, and here we have successfully taken that to the mobile environment. And I think that's an important point for everyone to see here, that, in fact, you can successfully take the automated collections to the mobile environment. And this was an experiment on our part to see how successful this would be, and, in fact, it has turned out to be quite successful for us.

Double red cells, we don't do a lot of these. That is not because so much the donors don't want to do it, but we have not pushed that. Mostly these have been O negative donors that we have asked to do the double collections.

Platelets, 9,786, and, again, you can see we've successfully or partially successfully taken that to the mobile environment as well, and then the double collections. So we've had a total number of collections of 163,000 in the last year which produced, excluding the partial products from whole blood, almost 180,000 products.

Now, if I just take the apheresis collections out of that and I take all of them, and we look at the total number of apheresis or automated collection procedures at our center, that represented 33,000 procedures, and they produced 39,000 products. In fact, it's a 1.5 to 1 ratio, and I'm not including partial products, that is, either on the whole blood or on the platelet side. And so that is effective--in fact, we have to do that to be cost-effective, as I will show you in a moment, because of the costs involved in the additional time and the disposable costs with the automated collections. And here I'm just contrasting the single plasma and the double plasma collections, again, showing you the numbers and where they occurred, the same with the platelets and the single-donor platelets and the percentages.

Now, what about the cost of the technologies? I was asked to at least discuss this to some degree.

One of the considerations with the automated collection technology is the increased disposable costs. And I'm contrasting that to what it costs most blood centers to buy the triple bag into which the whole blood collection occurs. The average cost of that bag, it could be as low as $5.50 in some of the very large centers, but let's say it really is between $6 and $7.50, depending on the size of the center.

With the disposable costs for the automated collection, they are running anywhere from $100 to $165 for, for example, platelet kits.

The decreased testing cost is a plus where you do double products because you only have one testing cost. And the average cost of the reagents and tech time in most centers is between $15 and $25 per donation.

One of the problems we have with automated collections is the reduced donor throughput, and a term that we like to use, the needle-in, needle-out, for whole blood is about eight minutes. But the needle-in, needle-out time for an apheresis donation, depending on the type of donation, could be as short as 25 minutes and as long as 90 minutes or even sometimes longer in doing double products.

There's also an increased cost to recruit these donors up front. They generally come out of donors who have been donors. You have to do a number of things to convince them to become donors. But once they do become donors, they really become frequent repeat donors if they buy into this. But apheresis collections are not for every donor, and I do not believe they will totally replace 100 percent the whole blood collections for a long time.

Now, let's take a look at the revenue and the costs, and Dr. Penner made a comment earlier which I totally agree with. One of the best deals going in medicine is the processing fee currently on a unit of red cells. I believe that red cells are vastly underpriced. And when we look at what it costs to collect a unit of blood--and this number of $115 to $135 per unit would surprise many people, and it may surprise some of you in this room, believing that our costs could not be that high. But, in fact, you survey most large blood centers, you'll find that clearly they fall around $120 to $125 as the total costs that are involved in the collection of a unit of whole blood. And I'm putting all costs into that within the blood center that relate to whole blood.

But the revenues that are derived, let's assume that 100 percent of the red cells are used as such and you derive $80. The fresh frozen plasma, only about 30 percent of that is transfused as fresh frozen. That brings about $9. About 70 percent of it, however, ends up as recovered plasma, fresh frozen, so its overall allocation is another $9, and the platelets, about 60 percent in centers that are using whole blood-derived, generates another 18. So the average revenue is about $116 per transfusable unit of whole blood. And that is below the cost.

And if you believe that we will switch more towards single-donor platelets, for example, because of leuko-reduction, and we take this part of that out, we may get a couple dollars more for that plasma that's on the platelets, but, in fact, the situation worsens for us. And if it's red cell-driven--and it is red cell-driven--then the costs of red cells is really quite low. And I have not included in here the cost of leuko-reduction. Our cost for leuko-reduction is in the range of about $20 to $22 per unit of red cells.

Now, if you look at the revenue from apheresis red cells, if it's $80 for--this is the non-leuko-reduced--then you've got about two times that or $160. But the cost to collect, factoring in disposable costs, additional recruitment, additional time, you still are going to end up just about breaking even, somewhere around $150 to $170. And you now have a donation interval of 112 days.

If you collect red cells plus plasma, if you get 500 mls of plasma, it depends, again, what the processing fee is in the particular area, then we can bring about $85 as an average for that triple plasma or double plasma, and it's totally worth about $165. But, again, when you put the disposable costs in, you're sitting right in the middle of that. So, again, it's basically a break-even.

Now, the conclusion, at least in our blood center, is that there is no question that apheresis technology can result in more blood products per donation, thus increasing the total number of blood products from the same number of donors. But the cost of this technology, at least for now, does not significantly reduce our costs to generate these blood products.

Thank you.

DR. CAPLAN: Thanks, Ron.

I have to ask you just a factual question. It must be me being dense. The double red cell donation that goes on, why is it in two arms as opposed to one to get--

DR. GILCHER: It's a one-arm procedure.

DR. CAPLAN: It's a one-arm procedure. Okay. Just double the mass of the cells.

DR. GILCHER: Yes, just double the red cell mass that's collected.

DR. CAPLAN: All right. Opening the floor. John?

MR. WALSH: Ron, what do you think the fair price of blood should be?

DR. GILCHER: Well, that question was asked a little earlier, and Susan Wilkinson dodged it.

[Laughter.]

DR. GILCHER: I honestly believe that pre-leukocyte reduction, I believe that a red cell should be very close to $100, depending on what part of the country you're in. I think that really would more accurately reflect its value, and certainly as a leuko-reduced product, in the range of $120 to $125. There may be some people who would disagree with me, but I think that more accurately would reflect the real costs in a red cell.

DR. PENNER: Ron, you might want to also add what the costs are if the hospital were to add it on to that unit of blood to give you a perspective on what the actual cost of the product is.

DR. GILCHER: What Dr. Penner is referring to is what the hospital charges for that units, and you're absolutely right, John. And I avoided that because at one time we, in fact, wrote into our contracts with the hospitals that they could not add anything to our base cost, our processing fee. They could add supplemental costs. But now that's all gone by the wayside, and so what you will find charged could be anywhere from what the blood center charges to as much as two times that amount.

DR. PENNER: I'm thinking about the type and cross and ancillary additions that are part and parcel of giving any blood transfusion, which in some cases outweigh or come pretty close to the cost of the product itself.

DR. GILCHER: In most places in the country, of course, what's charged and what's received are two different things, as we know. But the charge for a cross-match runs anywhere from four--well, maybe as low as $30, but on the average, $40 to $50. You think about the cross-match against a unit of red cells, and all the technology that had to go into the production of that unit of red cells from the collection to the point where it reaches the hospital, that's a staggering difference in my opinion when you have a $40 or $50 cross-match charge and you have a unit of red cells that's currently $75 or $80.

DR. BUSCH: Just to throw in--I won't be here tomorrow, so I'll throw in a little bit on cost from just a local center's perspective. From a person who's kind of more involved in research, but, you know, on the side lives with the operational people, our region used to--the cost of a unit of red cells had gone up progressively to meet costs of the center to a point of a little over $100. This is in the early '90s. But in the last, you know, five, seven years, both the hospital mergers resulting in buying groups that cross territories and drove down prices and the competitive elements within our own industry, we're now down at, I think, an average selling price of about $85. So the cost of a unit of blood has actually declined about 15 percent, at the same time as we've added tests, we've added costs, and as a consequence we've gone through two mergers with regional hospitals where we've cut staff, regional blood centers, and we've outsourced testing, and we're basically surviving from payroll to payroll, not knowing if we have enough money to pay our people. People haven't gotten raises in two years, three years, four years, and it's just a very bleak environment in the typical blood center these days.

DR. GILCHER: I'd like to add to what Dr. Busch said and say that as our blood center is a member of ABC, as is his, that virtually every large blood center in the country's bottom line fluctuates either just slightly into the black or more frequently into the red these days.

DR. GUERRA: I'd just add another note of bleakness. I think that in terms of the Red Cross experience, I can only second what Ron and John have said. I think it's an unusual situation when our basic product in the profession or the industry is priced so low below what the costs are, it's really not the way to run the railroad. Certainly the Red Cross, our red cells are priced well, well below our costs, and it has to be made up otherwise, or it cuts into the operation, as Mike just said. It just doesn't make a lot of sense. The price needs to go up.

Two questions, Ron. The first one has to do some with the technology. How often is it changing, and what cost in terms of the capital investments that have to be made by these centers just to keep up with some of the equipment that you showed in some of your slides?

Then the other question that I have, which I think is a dimension that we haven't really explored, is given the tremendous benefit that blood and blood products bring to the health and well-being of people, the many different conditions for which these products are used for treating conditions that in many instances could certainly be life-threatening or perhaps without them, you know, lead to the death of individuals, have we assessed what society's willingness to pay is in terms of blood and blood products?

DR. GILCHER: Well, let me take the second question first. I don't think we have assessed that. I think we're being driven by the payers who are trying to reduce what they have to pay. And so they are making demands at the hospital level, the hospitals are making the demands to us to lower our fees, do not want to pay for any of the new technology, whether that's the type of technology about which I spoke or the testing technologies that we've heard about, the NAT, nucleic acid testing. I don't think we really have made that kind of assessment.

What I can tell you from personal interviews with patients is that they say: I want the same kind of risk with a blood transfusion that I want when I fly in an airplane. I want that risk to come as close to zero risk as possible, and I'm willing to pay for it.

Now, that's what they're saying, but I don't know that anybody has really quantified that with any kind of statistical data. And then, again, if it was done, would it fall on deaf ears?

The first question, which relates to the capital equipment costs, you have the capital equipment costs, you have the maintenance cost of these pieces of equipment, which is, in fact, very significant, and then the disposable.

The reality is certainly with our blood center, and I'm sure it's true with most of the other people in this room who represent blood centers, is that what we do is we bring those first two costs most of the time into the disposables, so that if we are doing X number of procedures per year, it includes then the capitalization of the equipment along with maintenance costs. And so when I call it disposable cost, it could vary from one center to another, depending on their approach to whether they buy the equipment outright or they, in fact, incorporate it into the disposable--the number of disposables that are used.

But it's a significant cost for the equipment, and it's a significant cost for the maintenance on this kind of equipment.

DR. HOOTS: I don't know if we are finally getting around to one of the right subjects or if we were just a little prescient, but if you look back to what Dr. Sullivan showed on the slide, when the lines cross, the rules change. And suddenly a not-for-profit right becomes a bidded commodity, and it seems like we have a tremendous challenge here to make sure that that clearly just never happens, because that's the quickest way for you to get what you deserve for a unit of blood, is for it to not be available to everybody every time.

You know, that would be--I mean, not only would this society have a right to ask why, but clearly if it's happening as quickly as it appears to and if we hit the wall that Jim talked about as quickly as it looks like we're moving towards it, then that's exactly what's going to happen. Then everybody is going to be asking how in the world did we get here.

DR. HAAS: I guess my comment relates to that in the sense that I guess I'm not saying anything that no one doesn't already know, but we're dealing with a product where we just can't throw it into the marketplace.

The comment was made by Ron that while the hospitals are forcing us to keep the price up, but there's another little agent out there called insurance companies, and we don't have a situation where in a typical market situation the community can express its willingness to pay because we have multiple types of operations of work, and in trying to answer the question that Keith has raised in an incredibly complex question which I don't think my discipline knows about either.

DR. KUHN: I guess this kind of comes to the question that I have had and I am hearing, but I'd like to have a more definitive answer to it. Who regulates or sets the cost for a unit of blood, number one? And then how have we been able to increase in the past 20 years the cost of a unit of blood two-fold? What's the formula here, and how is that--how can it be increased again? That seems to be--going two-fold in 20 years or 25 years doesn't seem to be much.

DR. GILCHER: I can comment. I don't know that my comments are totally correct. But when you run a large blood center, as I do, again, you take your total operating costs for that center. You look at the products that you need to collect to meet the needs in your community. And then you try to figure out what each one of those is worth and put a value on it and what it will bring back.

For example, the plasma from the whole blood only 30 percent of the time brings a higher value as a fresh frozen plasma, that is, direct transfusable product. When it goes to recovered plasma, that price or that value is not determined by us in our own marketplace. That's determined in a sense by a global marketplace for that part.

So we have to take into account how much of that plasma we're going to use as a direct transfusable product, then what's left, we don't want to throw it away, so it goes into the recovered plasma market.

That price is set clearly at a global level, and it has nothing to do with us. So then we set a price, a processing fee, within our community that allows us hopefully to have a bottom line that has a very slight margin, and, again, in the comments that Susan Wilkinson made, the written comments, she talks about a 4 percent bottom line. We haven't seen 4 percent on the bottom in the last five years. And that does reflect and make it difficult on us to, in fact, buy new equipment--and I'm talking about things like cars and vans that are needed to go out and do the blood collections or deliver the blood products.

DR. GILCHER: I'm sure there are other blood bankers in this room that would like to comment as well.

DR. BUSCH: And I think the reason, what's fundamentally changed in our business, in truth, is not something we can blame per se on the hospitals or the insurance companies. They need the blood. The reality is what's hit our field is competition between ourselves; the classic divisions between regional blood centers that basically control their own donor base, and you have the hospitals in those regions have broken down as hospitals have merged, and as blood center programs have become more competitive.

And what's happened is, is we have driven our prices down, and we've lost money in the last 5 years because we've had to maintain the hospital market shares, and we've reduced our costs to maintain those shares because of competition from both national and regional blood center competitors.

So it's easy to blame these other organizations, but the truth is our own competition has facilitated it. They couldn't have reduced the prices had we not been willing to compete and lower prices against one another.

And the last comment is, in the last few years now we're finally pushing through some cost increments that are associated with very expensive technology changes. So here we're talking NAT, and we're going to raise prices $7 or $8, which the hospitals are screaming about and barely can afford. But it's going to cost us at least that to do it, and then we'll come to completion. So in terms of the margins, we're not going to improve those with these changes.

I don't know the answer, but the competition within our own industry is a major factor that has driven this.

DR. CAPLAN: That may be a good note to take maybe two more comments and then move over to the statements from the Red Cross and America's Blood Centers. But I was going to not ask a question so much of Ron as I was thinking along the same lines that Mike Busch was. I don't know if you noticed, we mentioned organ, solid organ distribution, and there has been a discussion about changing the distribution system of organs to more national distribution system in the face of scarcity. And what ten states have done so far, and I bet more will, is pass laws sequestering their organ supply inside the state boundaries.

It is not too hard to imagine when the curve drops that states, not Federal, but state regulation, which say if it's regionally collected or locally collected, it will stay here, and that's what we want to see by state law. I'm not endorsing it. I happen to be a critic of the Balkanization of the distribution of medical services, but one might say that if we don't get some attention to these structural features, the distribution, the cost of shortage might not be born so equitably.

DR. PENNER: I think both of the comments, yours and Mike's, are on the recruitment issue for the donors. Essentially, we had a community hospital, we had community blood donors, and we had a community blood service program. And as I think Ron was bringing up, you tried to set the price at your center that was reasonable, and it was not-for-profit, and the hospitals looked it over, and they said they trusted you because you were providing the blood, and if it had to go up $5, they would go along with it, and there was no competition, no concern.

And getting the donors in that community was much easier because it was a community blood program, and they knew it was going to their hospital, and it might be the kid down the block that was going to get the blood. No problem on bringing people in.

Suddenly now we've got the HMOs, and they are going to say, "Well, I'm going to get my blood from Texas" or "I'm going to get it from Oklahoma" or whatever, because they can give me a lower price than you can. So you either have to meet my price or we start shipping it in.

Then suddenly the donors who are coming in are saying the same things, "Where's my blood doing?" and I've had a lot of them come in and ask, "Is my blood going to Los Angeles? I don't want it to go to New York. I want it here." And then also they get the same comment, they say, "Is my blood coming from Detroit that I'm going to get?" the recipients. So that community localization has been quickly dispersed, and I think that's why we're facing the problem on maintaining the donor population and running into the same problem on costs and how we are going to be able to get an appropriate cost back for the product that we are delivering.

DR. DAVEY: I would agree. Just expanding on what Mike said, I think that the competition, which we all are facing and, again, I think echoing what John has said, is really a result of managed care, not so much of I think the various blood centers are kind of growing at each other. We're at the mercy of the United States health system that's affecting us as well as everyone else, and managed care is driving it.

And, unfortunately, there is competition for the bottom-line dollar, and some of the collegial relationships that we had, and I think we'd all like back, are hurting because of that. It's the system that's hurting us as well as others.

DR. GILCHER: I'm going to make one last comment as the speaker here, and that is that I think what we're seeing is a tendency to try to treat blood as a commodity. I think that's a mistake. Very clearly, we believe that blood should be regarded as a local resource first, and once we've met the needs at the local level, and that's exactly been reflected, Dr. Caplan, with organs; that when the needs are met at the local level, then it's okay to let the blood or the organs or the tissue go outside the region.

But if people within that area are making the donation, they want to be sure that they are, in fact, covering that particular area. And I think that has been the way that most blood centers have, in fact, operated in the past.

DR. CAPLAN: Okay. Thanks, Ron.

I think we've got the America's Blood Centers up with their statement next.

Dr. Bianco?

DR. BIANCO: Thank you. My name is Celso Bianco. I am the president of America's Blood Centers, and I am also the vice president for Medical Affairs of the New York Blood Center.

America's Blood Centers was founded--it used to be called CCBC--in 1962, and is a federation of not-for-profit independent regional blood centers. And the fundamental rules they had put together, this organization, were volunteer donors, a community-based board of trustees, and individual FDA licenses. So each one of the centers is responsible for each one's organization, quality and service.

It collects about half of the blood supply in the country. Last year our business centers collected about 6.5 million units of whole blood, and about one million liters of plasma are shipped for the manufacturer by ABC centers.

ABC members provide a number of services from transfusion therapeutic services, depending on the centers. They have some substantial research centers, and some of the members are totally committed to the safety of the blood supply.

Also, we want very much to--I think what we heard in the last hour or so in discussion is, for the first time I think in years, we have been matching things. We are talking about the issues of availability of products to those that need them, and we are talking about all of the implications from costs, competition and everything related to it.

The realities that we are fronting is that blood is as safe as it has ever been. ABC, for instance, serves as the umbrella organization for 16 independent centers among the 73 centers. They are implementing the testing and providing it to other centers in their regions and to hospitals even that collect in their regions.

And blood centers continue to invest not only in NAT, but they continue to invest scare dollars into cGMP quality program, safe products. And despite all that, blood shortages essentially are worsening. I think that actually it is a very interesting piece of data that Dr. Alan Williams did not interpret exactly like that. But as we saw the increasing what he called the incentives in recent years, I think is a reflection of increased difficulties of recruitment.

The questions that are here before the committee and that were alluded to by Dr. Nightingale was what is the reserve supply of blood? What can be done to enhance these reserves? What actually is in the back of our minds or my mind is can we survive a 5 to 10 percent hit? Would it defer individuals who visited the United Kingdom because of a theoretical risk of CJD?

And together with those questions, we look at the many reasons and the many solutions that have been proposed, for instance, here before the committee, an increased number of donations, evaluate the incentives, increase yield, hemochromatosis, acceptance of donors with hemochromatosis and examining the potential contribution that we will have from blood substitutes.

Our position is that we obviously agree with each one of these approaches, and we believe that each one of them can seriously contribute to an increased blood supply. We are placing substantial effort in donor retention, customer service and new technologies from blood collection. I am very proud to say that Dr. Gilcher is a member of ABC. However, we believe that there are additional issues that have to be considered as we discuss blood donors and blood donations.

There are many other reasons for these shortages or potential reasons sometimes because the evidence is not as clear. It's an aging donor population. Corporate downsizing, complex and lengthy donation process, a shrinking eligible donor population, competition for donors. I'm not just talking managed care competition, but competition for donors and a shaken public confidence in the system.

Even some people who have asked and continue asking will paid donors solve this shortage of the product. For instance, the plasma industry has made remarkable progress in dealing with the higher market rate that they have for their first-time paid donors. They have an effective system of repeat donations, 60-day quarantine, viral inactivational products. We cannot apply any of these processes to our cellular product donors, to red blood cells, platelets and granulocytes.

So, essentially, the volunteer blood donor is an essential part, in our opinion, of the blood collection system in the country in terms of maintaining the safety of the blood supply.

In the '60s, 25 percent of the patients receiving multiple red cell transfusions had hepatitis. Blood shortages were still major issues, and there were paid donors. The change to volunteer donors diminished the rate of hepatitis by half, and that change was made worldwide and, to date, a vast majority of blood donors around the world, whole blood donors, are volunteer blood donors, and we see the effect of that.

It actually was mentioned here a few minutes ago. The difference that we see between the market rate in the general population and the market rate among the donor population, a hundredfold to a thousandfold, a hundredfold difference in terms of prevalence of infectious disease markets. This was shown this morning by Dr. Klein, showing the impressive decline in the rate of hepatitis among recipients, with a succession of all of the measures that were introduced.

We talked about incentives and recognition. And I thought that the data presented by Dr. Williams was extremely interesting. I just want to make a little point. There is a difference between recognition and incentive, as we see. Donors must be recognized. They must feel good about what they did. They must know that we recognized their service to the community. A t-shirt that has Coke or Pepsi written on it may be an incentive. A t-shirt that says, "I donated blood today" is recognition.

We have been hit very hard, and I can say this specifically for the area of New York, by the downsizing of corporations. Corporations represent a major component of the volunteer donor campaign because the corporations not only provide us with a site for the donors, these large companies provide us with a tremendous amount of support, the internal support, logistic support, space, people to get everybody enthusiastic within a company like J&J or Met Life in terms of donating blood several times a year in large drives.

These same corporations are under increased pressure for themselves to reduce their costs and to limit the investment in community services, and for them the donation process is lengthy, demanding and stressful, and it is, and we discussed a little bit of this. Why do we need to treat donors so specially? The environment where the donor is, is surgical, the finger stick hurts-- no matter what people say--the questions of medical history are uncomfortable, and the needle stick hurts. I donate blood very often.

Competition is increasing, and what we see is not just competition for hospitals looking for blood suppliers. We see competing collectors fighting over the same donors and the same donor groups. We receive increased complaints from corporate groups, and their treatment almost as if--there is no evidence that that competition--often we say, in a freemarket, that competition improves the quality of service, improves the products that we do. There is no evidence, that I know of, that competition enhances the quality or the volume of the blood supply.

And there are many other issues that we have in the environment that we are--some very correct--that scare donors, and scare recipients and make it more difficult to collect blood; issues of compliance. Even when we are satisfied that we did our job with HCV look-back, but every time that we are talking about that or massive recalls or public health announcements like we had to do in New York, we scare the donor population. We can see, as we follow our collections, a decrease in the number of donors that show up.

Even an event like we had a couple of weeks ago--I don't know if many of you saw an event on Palo Alto in which a nurse very diligently washed needles with hydrogen peroxide. We were called, and we were asked by reporters on television if there was any risk of donating blood related to that.

Advertisements from manufacturers, even of the products that we use, scare people, and they raise concerns about it, be it plasma, be it filters; that is, you go to the hospital and ask for such a filter that is better for you, and if your blood is not tested for that disease, you may be in danger. And they even be a result of scientists in search of funds, and I don't think that many of us forgot ICL or idiopathic lymphocytic people.

We have a shrinking eligible donor population. The medical history questions and the deferral criteria give more important theoretical risk to the impact on the donors and on the donation process.

We appeal to the donor's deepest feelings, and then we treat them like raw materials for pharmaceuticals. Our phlebotomists are focused on compliance, and that's the rule that we follow. They are not necessarily focused on the customer service and bringing these donors back to donate again in a few weeks.

However, if we ask the question, have we reached the upper limit in blood collections because of all of that, definitely not. If we look at the examples, in Denver, a couple of weeks ago with the horrible things that happened there, there were 1,400 people on line at the blood center in Denver that stayed up the whole night. The Denver center stayed up the whole night because nobody was going to go home until they collected their unit of blood.

I wish we could, in a certain way, transfer and better understand that sense of community. The blood supply is there. We have not reached our masses. People care about their community. They need a good reason to give the gift of life, and we are the stewards of the gift of life, and we should apply substantially more resources to impact the good will of the community.

We need to invest, we need to have these funds that we are talking about. We need to invest in behavioral studies. We need to invest in advertising. We had a short experience in New York with radio advertising during the summer last year. We couldn't afford to continue. But certainly it increased the awareness, increased the amount of donors.

But our limited resources lead to limited direct investment. We need contemporary behavioral studies of blood donors. We need effective advertisements besides the public PSAs, and we need improvement of the donation process, and even on the environment where we collect the units from these donors.

Just one comment about what we are going to discuss tomorrow, so we have the opportunity to express our opinion. ABC believes that most people with hemochromatosis are safe donors. However, we are concerned that a person with hemochromatosis may conceal disqualifying conditions in order to get a free phlebotomy. Ultimately, if insurers and HCFA paid the cost of phlebotomy for individuals with hemochromatosis from dollar one, they didn't have to assume the responsibility for that, there will be no incentive to distort medical history, and I think that hemochromatosis individuals will be perfectly safe donors and may make a tremendous contribution to the blood that is available.

The final thing, and actually I change the statement that is there because I did not know exactly what Dr. Satcher--in the printout that you received--was going to say this morning. But ABC applauds Surgeon General Satcher's recommendation that reimbursement keep pace when blood safety measures are introduced. A strategy such as recalibration of blood-related DRGs can bring America closer to a zero-risk blood supply goal that all of us share.

Thank you.

DR. CAPLAN: Questions? Comments?

I was curious, you know, some time ago based on no behavioral empirical evidence in the organ, the notion was introduced that when someone donated or there was a donor family, there is a letter that goes out from the HHS recognizing them. They get a little certificate. Has there been any discussion of that sort of thing, aside from local t-shirt recognition in the blood world?

DR. BIANCO: Oh, there's a lot more that is done. It is from t-shirts and mugs to special celebrations that are made particularly with rare donors, for instance, meeting donors and recipients. This is done a lot with bone marrow transplants, but we are doing more and more with blood donors in identifying recipients that can help us in blood drives.

It is a science and an art, recruitment. And there are some very good recruiters. I think that the issue is not so much not knowing what to do. I think that the issue is not having enough resources to invest in that system. People that have the resources, like sell cereal boxes, they sell a lot of cereal boxes. If we invested as much as they did, we would have a lot of donors.

DR. HERBERT: There's a misapprehension I'd like to correct. You stated, as have many others, falsely that people with hemochromatosis will give blood, concealing if they have hemochromatosis in order to get a free phlebotomy. That's not true at all. I'll bet you cannot find more than ten such cases in the entire United States because if you go to any blood bank, ours at Mount Sinai, any of yours, and you do transferring saturation on every patient you have accepted as a donor, you will find that 10 percent of them are heterozygous for hemochromatosis and 1 in 100 is homozygous, and all of the blood banks are giving that blood and have been ever since there have been blood banks, not knowing this hemochromatosis blood.

DR. BIANCO: Maybe I wasn't clear in what I said. I didn't say that they lie. I said that this would be an incentive of people not to be entirely truthful, and I am basing that, for instance, on the experience that Dr. Williams provided; that 98.1 percent of the donors say exactly the truth when they respond to medical history, but that we have 1.9 percent that may not exactly review certain things.

DR. HERBERT: Correct, and not one of that 1.9 percent is a person with hemochromatosis because they don't know they have it.

DR. BIANCO: Well, I understand what you are saying.

DR. PILIAVIN: I think Dr. Bianco was referring to if the people knew that they could get this service, people who know they have hemochromatosis and who have to pay a lot of money now for their phlebotomies, then they might be very tempted to do it given the very large costs that are involved. He was not suggesting that they do it now.

DR. CAPLAN: I promise you we will wrestle this one tomorrow. We'll revisit it.

DR. GUERRA: A couple of questions, Dr. Bianco. Again, thank you for an excellent presentation. It certainly provided very insightful information.

The structure of the boards of the American Blood Centers, we haven't heard too much about that. Are those representative of communities, of the industry, is one question, and the other, what might some of the lessons learned be that you could share with us in terms of those centers and communities where they have been successful in maintaining an active and growing donor pool.

DR. BIANCO: In the first part of the question, all boards are local boards and, in general, centers look for people within the communities that could be very helpful in their donor campaigns and any in helping them manage the entire process.

Actually, I know I have a limited knowledge of their boards, but there is so much interest that, for instance, many members of ABC will bring some of their board members to our annual meetings so that they continue to be informed about all of the things that happen in our field. There are programs that are very, very successful. You are sitting next to one, Dr. Gilcher probably has one of the most successful programs within ABC. There are programs in Florida that are very successful.

The programs that have been the most successful are in stable communities, have not confronted tremendous competition from outside, from other groups that came to compete for the same donor base and have focused, and I hate to say customer service, but on a direct interaction with the donors. Because donors--I think Dr. Piliavin used to say that or still says, donors don't like when they are asked to do so by somebody else.

DR. PILIAVIN: Actually, that was Al Drake who said that.

DR. BIANCO: Al Drake. And so it's a direct interaction. It's a lot of work because it's not simply pulling out a $10 bill. It's sticking your arm and letting somebody do some things that are not always that pleasant. However, the feeling of elation that you have at the end is what you have to capitalize on; that is, the pride that you did something so important as donating blood.

But there is a tremendous experience in terms of blood collections. I wish, or the only fear I have sometimes is that we may lose some of that interactive capital as we stop investing in that, and these people move to sell cereal boxes.

DR. CAPLAN: Thank you. Let's move on to our last speaker before we take a short break, and then we'll go back for the public comment and some committee discussion, and this is the American Red Cross.

DR. DAVEY: Thank you, Celso. I am going to have a lot of trouble competing with the audiovisual extravaganza. I have six overheads with big print, and I'm not sure it all reflects the relative financial situation of ABC and ARC, but we'll give it a shot.

[Laughter.]

DR. DAVEY: I just want to comment briefly, from the perspective of the Red Cross, which I think is a perspective of many people here on some of the issues we have with the donation process and our donor supply in the United States, and many of the issues have been touched on in much more detail by other speakers this morning.

Just in terms of the Red Cross, we do collect about six million units of blood per year from about four million donors. That's a little less than half of the nation's blood supply. Applying some heavy mathematics, that comes out to 1.5 donations per donor per year, and that's where we stand today.

So, clearly, there are two ways to improve this situation; recruit more donors, increase the four million number, or increase the donation frequency, try to get that 1.5 donations per year number up a little bit, and we are trying to approach increasing our donor base by both of those methods.

Again, just a very brief bit of data. We are finding our first-time donor situation, as demonstrated here, it's gone up a little bit from fiscal '97 to '98, where our first-time donor rate has gone up from 14 to 16 percent. I think Marian, Ms. Sullivan, said roughly in the country it was around 20 percent. This is the Red Cross experience. That's good news. We need first-time donors. Every donor has always been a first-time donor. And as our older donors move on from the system, we certainly need to have that percentage stable or increasing.

On the other side, though, our penetration rate, the number of collections per hundred population or percent of people that donate, if you will, has dropped a little bit over the last year from 6.4 to 5.7. That's a bit of concern. It looks like what we're having to do is just work harder with larger groups of potential donors to achieve the number, the yield, that is sufficient to meet our needs.

We have some issues that impact on donor loss. Some are generic to the profession in the industry, some are maybe specific to the Red Cross, that are going to affect our donor base. We have, in the Red Cross, we have a fairly large potential loss facing us, as we are considering moving from an ear stick to determine hemoglobin determination in the donor to a finger stick. This doesn't seem like a very big deal. Both are permitted. But actually, in doing so, we feel we'll have about a, perhaps, up to a 5 percent donor loss because the finger stick will give us a determination that, perhaps, is a bit more accurate and will not overestimate the potential hemoglobin that may be used to qualify a donor. So we are looking at a substantial loss if our system moves from an ear stick to a finger stick for hemoglobin determination.

At the moment, we are implementing NAT, Nucleic Acid Testing, in the system. It's under an IND. We are asking our donors whether or not they want to participate in having a NAT done. At present, we feel we have to do that until NAT is licensed and approved, and some donors actually are saying, no, we'd prefer not to do that, for a number of reasons. They fear they may be deferred, their not happy with being a part of a research protocol. No matter how we word it, we're losing a small number of donors. We hope that will be corrected in the future.

We have heard a lot about the possibility of deferring donors who have been to Britain or who have lived in Britain. That is a cloud over our heads that we hope will not rain too heavily on us, but we certainly could stand to lose, as you've heard, up to 11 percent of donors if the most drastic possibilities that the TSC Committee are considering are actually put into operation.

I think, also, I would like to stress a little bit more than perhaps we have heard today about our donor questions. We are looking at that. I know the FDA is looking at the questions and their accuracy and validity. Alan Williams and Dr. Piliavin have certainly spoken eloquently on this issue. But for sure our donors are faced with an inquisition now of incredible complexity and quite a bit of intrusiveness. And this could be getting worse. There's a lot of debate now about malaria questions, whether they should be increased in scope and complexity. It's a tendency that if the donor questionnaire becomes increasingly complex that we're going to be, number one, finding donors who don't understand what they're being asked, which I think we already are finding, and others who are going to be turned off by having to answer this large questionnaire, and repeat donors who have to come in time and time again and answer the same questions over and over again.

And we do get complaints from good donors, long-term donors, saying I just don't want to answer questions like this again. I would rather not do it. And I think we can get around these problems by perhaps looking more carefully at the donor questionnaires and modifying them appropriately using behavioral science and validity evaluation to target the questions appropriately.

Another issue I'd like to mention which hasn't been brought up today which really impacts our donor base is actually the complexity of testing that we do today. We have an excellent, as you know, a superb series of tests that we use to identify viral markers and other markers in potential donors. One of the, perhaps, downsides, if you will, of this complexity of testing is that some tests don't have confirmatory tests. Other tests are being upgraded, manufacturers change. There is a whole range of nuances that a donor can face in terms of test marker positivity, confirmatory testing, license testing, et cetera.

So I think all of us in the profession have found that many of our donors may come in, donors who have been longstanding good donors, and run into a test result that perhaps is a false positive. A good example is, in recent years, the influenza shot, the flu vaccine, cross-reacts with the anti-HTLV test. That's been improved a bit. But over the last couple of years we lost a number of donors because they come in after a flu shot. Their HTLV test will be positive. According to regulation, they are deferred. That makes donors unhappy. They are in to give a gift of life, they are in to help, they have been donating for years, and they get a message, "Sorry, we don't want your blood any more."

I'm afraid the angry donor is something we really need to avoid because one angry donor can have a ripple effect in their community. It would be a little different, the flip side of what Ron said, where we want to be engaging groups and rewarding groups. An angry donor can go back to his or her church or rotary club and say, "This is what happened to me. I don't like it," and that message gets around. And if we can continue to sharpen our testing algorithms, that may help us avoid the angry donor situation which I think impacts on our donor base.

We in the Red Cross would like, over the next year or two, to increase our donation frequency, it looks like modestly, 1.5 to 1.7 donations per donor per year, but that's a 10 percent increase. We've heard from Dr. Gilcher and others that there are some really innovative technologies now to increase the yield, perhaps, per donation. Ron went over that very elegantly, double red cells, et cetera.

We also think we need to look at where we are drawing the blood. We certainly rely very heavily in the profession in recent years on the mobile blood donation drive, and we will continue to do that. We need to get the donation site at the place where the donor can come and be a donator, and we will continue to rely on that, hopefully using again the more mobile apheresis technologies to enhance that experience.

However, we also think that there is an increasing need, perhaps, to look again at the fixed-donor site and to really target some very nicely furnished, refurbished, newly built, fixed-donor sites in areas where we feel that it would be most convenient for our donors to come in and donate frequently, donate in the more advanced technologies for stem cells, double units, jumbo plasma, et cetera. It's also better in terms of staffing. Nurses would have to just come to that site, work their shift and gone home instead of driving two hours out into where a mobile site may have to be. So we think staffing arrangements can be better managed. The donation experience perhaps can be better handled in fixed sites if they are properly chosen and properly furnished.

Again, an issue that was brought up earlier today targeted efforts to increase a number of donations per drive. One thing that impacts on our donation capabilities are really drop-in donors. It's very important to schedule donors, it's important to give donors a repeat donation date, it makes the drive more efficient, it increases the donation number per drive, and donors like it better because you don't run in and wait for an hour/hour-and-a-half behind another line of donors, just like you might at a doctor's office, and it makes them upset and the donation experience not as good. Scheduling at the time of donation and for the next donation is very key.

Another issue which makes the donation experience better we feel is automating the blood donation record itself, the questionnaire. There's been a lot of emphasis, a lot of work, at looking at a computerized, if you will, blood-donation questionnaire, where a donor can come in, in an appropriate setting, just go through a computer questionnaire answering the questions that are now taken in most cases by a live donor. This is a different psychological setting, a different situation, and I think there are data that people answer questions a little bit differently when they are not confronted by a person, but instead by a computer. So this is an area that will make the experience, we feel, and we would like to see that a whole lot more effectively in the future.

We have some plans to recover our lost donors. Specific to the Red Cross, we now are going to be very aggressively reinstating donors that have been deferred in our system for elevated ALTs. We have been able to do that in the profession for a while. But because of issues in the Red Cross about getting a uniform information system across the country, which we now have, we have delayed implementing this. So we are optimistic of being able to reenter a number of donors who have been deferred for ALT and stop having to defer these donors in the future. That will be a big gain for our system.

Also, we feel that, again, the first-time donor, getting them to come back, one of the targeted areas is the high school. I think most of us, again, in the profession find that a high-school drive can be very effective. A lot of kids come out. It's a thing to do for the high school, and it's a very positive thing for a high school. But there is a real drop-off for those kids coming back as a second donor. It's a major drop-off. And I think if we focus on the high school, get them to come back for that second time, begin to reestablish in them the habit of donating perhaps as a lifetime early on, we'd be making some good headway.

Also, it would be very nice, along the same lines, to see if we can work with Departments of Education and schools, this is a big topic, to maybe focus a bit on blood donation in high school education health classes, in high school health classes. I don't think that's covered, to my knowledge, very much at all anywhere in a high school curriculum. Maybe it might be hard to that, but it would be nice if we could talk to our Boards of Education and say, look, as part of your health education, talk about blood donation, the importance of it, begin to target, encourage high school kids to think of this as a civic responsibility and why it's important, again, at an early age.

And, lastly, kind of lumping all together things we've really heard about that are very important, we really need to understand what motivates donors. We need to be working with behavioral scientists, understand about why certain ethnic groups like to donate or don't like to donate for certain reasons, what about incentives and rewards, all of those things we've heard about are very important and need to be addressed.

Lastly, I've listed a couple of things here, these are not necessarily pertaining to the Red Cross. They are more, I guess, my thoughts about some donor-enhancement options. Some have been mentioned some, but now we really have to think out of the box these days on how we can maybe begin to attract and retain blood donors.

We've talked about validating and streamlining screening questions. We've touched on that. Paid or pedigree donors. Paid donors are kind of anathema in the American blood supply for very good reasons that have been pointed out in detail earlier today. But there are examples in the United States at the Mayo Clinic and the University of Iowa, very selected populations, where paid donors have been, that particular technique has been used very effectively. I think it might be worth thinking is there a possibility of using pedigree donors or paid donors for very selected situations in our system in a more broad basis? We have to approach this very cautiously, but I don't think we should entirely ignore that possibility.

The second donation is so important, as we have seen, that maybe some incentives could be targeted specifically at that first-time donor who we want to get back for that second time. So it's that second donation that maybe will get that habit started. And perhaps looking at the first-time donor who doesn't come back, target that second donation, may be a good use of an incentive situation that may be more specific than just offering incentives across the board.

I mentioned modifying screening questions for repeat donors. It sure would be nice to have a repeat donor come in and not have to go through the big inquisition every time. And all of these things, I think, may go to the overall point of really enhancing the donation experience for our donors. We need to make the experience valuable for them. We need staff that makes the donor feel wanted. We need to have an environment that allows privacy and is comfortable. All of those things are very important. We need to make our donors feel as valuable as, indeed, they are for our blood supply.

So those are my comments. This is a I think a very valuable discussion we are having today, and if there are any questions, I would be happy to take them.

DR. CAPLAN: The floor is open for questions.

Jay?

DR. EPSTEIN: Well, as I have been listening to the presentations today, one of the dilemmas is that, as we implement deferral strategies for various reasons, we always have to consider what's the impact on the donor base, but we never seem able to get an answer to whether we could recover that deficit; in other words, what is the elasticity.

And, also, I am struck by the fact that we don't tend to think of it in kinetic terms. It's very different to get a thousand more units donated in the next 24 hours because there has been some accident. It's different to think about getting an increase over, say, the next season because it's the summer or it's mid-winter, and then to think about a totally different dynamic in the system as a whole. In other words, if we gradually implemented strategies that caused some loss of donations, over what period of time could we then replace it and sustain the replacement; in other words, a long-term issue.

I just wonder what some of your thoughts are about the real elasticity. And just to add one more point, we all assume that having more blood would be better, but it's actually not so. You actually don't want to collect more than you sort of have an obligatory need to waste. You know you have to be in a slight exit situation in order to meet fluctuations of need, and because as Harvey pointed out, not every unit is fungible. You know, you have blood groups, and you have got to serve each of those subsets and so forth.

But the fact is that, therefore, the concept that it would be good if we could just double it is entirely spurious because that would simply translate into waste, and that's in nobody's interest.

So I just wonder if you have thought about the whole kinetic issue, the whole issue of timing; in other words, having it when you need it enough, when you need it, and what's the short-term issue meeting urgent needs and emergencies crises versus the long-term need of phasing in replacement donation.

DR. DAVEY: Right. Well, I think those points are well-taken, Jay, and I would suspect that none of the speakers today would recommend, even if we could, doubling the blood supply. We would be wasting resources. But we are in a marginal situation.

We are very lucky here, I think as Harvey pointed out this morning, that we are dotting the "i's" and crossing the "the's" on safety. But at least for good portions of the season, as I think, I forget which speaker showed, we are in not only a marginal, but a deficit supply situation. Recruiting to cover those deficits has been an effort that's been focused on for years in the profession. Maybe we're not doing the right thing around Christmas or around the summer to meet those long-term dips, if I am following your question properly, and we need to do better on how do we attract donors during those times.

Clearly, having donors come in for an emergency or a crisis is good, but that's not something we need for the long term. We need to do better to iron out the dips, Jay. I don't have any other specific comments for you. I don't know about Ron or others.

DR. PILIAVIN: Again, this is not a question. It's a comment. I quite agree that having, even if you could engineer some kind of crisis every now and then in order to motivate people, it would definitely not be the right way to do it in the sense that people who come in to give blood under emergency circumstances are motivated completely differently from the ones who come in day by day, year by year, regularly giving blood. It's a completely different kind of motivation. The first is kind of a, oh, things are terrible, I want to do something. I want to do something right now because maybe I can feel a little bit better rather than the sort of general community, I'm a member of the community and it's the right thing to do kind of motivation.

The second thing is a comment with regard to two things that were said separately; one, about going after high school students because it would be a way to set up, possibly a good way to start a habit early, and getting them back for the second donation is the second way to do it and is a good way to focus on it.

And the other is the shortage issue. We did a brief study once a number of years ago in which we targeted high school kids who had given either once or twice during the school year and brought them in in the summer. And at least in Madison, Wisconsin, that pretty much wiped out the summer deficit that they had; it being a relatively small community.

But we also discovered that the ones who gave in the summer continued to give a good deal more during the next year. Many of them were not in college, and many of them were employed in the community. So there is something about continuity of donation across the whole year, we've discovered this in other research, is that it's not so much how many donations, but how they are spaced at the beginning of your career. If they are spaced relatively closely together at the beginning of someone's donation career, that's the best predictor of them continuing in the habit donation.

DR. CAPLAN: Let's do Fernando, and then we better let this gentlemen offer a comment, and then we'll take a very short break.

DR. GUERRA: Rich, have any population-based studies been done to try to identify the front end on the demand side what those conditions might be, either in communities or regionally, that account for the greatest use of blood and whether or not to try to better project what the needs might be in the future to see which of those conditions can be prevented in ways that will not put such a demand on the blood supply?

DR. DAVEY: Sure. I think one of the encouraging aspects of the last couple of years has been a decrease in use in the number of units of blood for surgical procedures that needed multiple units in the past. So that tendency I think is already well underway. And hospital transfusion committees, I think with encouragement from others of us in the profession, are really looking very carefully now at using maximum surgical blood order schedules and other technologies to really reduce the number of transfusions whenever possible.

We've come a long way there. We, perhaps, can do better. But reduction in the number of transfusions is certainly a good way to avoid the demand. Autologous transfusions are going down, number of transfusions are going down, procedures are going up. So I think we're on the track.

DR. MacPHERSON: Jim MacPherson, America's Blood Centers.

Jay, I wanted to take a crack at sort of responding as well to what you said. I think our problem is we cried wolf for so many years. As each new criteria came through that deferred more and more people, we kept saying, well, the donor supply is not elastic, and we're going to have shortages, et cetera, et cetera.

And, indeed, what we have done over the last 15 years is we have deferred tens of millions of willing donors, people who are either in the system and come up with false positive test or positive test, but false positive in many cases and lost very willing and perfectly safe donors, but erring on the side of caution, plus deferred tens of billions of people by just saying you can't donate because you're in a high-risk group. Every time we've done that, we've rattled the specter of shortages, and then every time we've been able to survive it.

The problem for us now is we're all standing up here and saying this time we really mean it, and this time there really are severe shortages, and this time there really are some problems. And so I think that we're hoping that our credibility is restored, to some degree, by the unanimity of the voices. And I think that we have to look at things much more carefully in terms of availability as we go forward. And, frankly, I think we have the luxury to do that with a very safe blood supply that we have.

DR. CAPLAN: Okay. Thanks. Why don't we take, literally, a ten-minute break, and then we'll come back for whatever comment we have, and then we'll do some discussion.

[Recess.]

DR. NIGHTINGALE: Could I see a show of hands, please, for those who wish to make public comment. I see one hand. Do I see any other hands? If I see only one hand--

MS. SWANSON: Good afternoon. My name is Julie Swanson, and I am president of the Alpha One National Association and an alpha patient.

I would like to express my opposition to the Medicare outpatient proposed payment system mentioned by Dennis Jackman of IPPIA earlier this morning. Patients with alpha one currently receive a weekly or biweekly infusion of a lifesaving, sustaining replacement product at an average cost of $1,000 per week.

Under HCFA's proposed payment plan, infusion costs would be bundled together and reimbursed for approximately $74. This wide discrepancy of payment would be a disaster for our community. A recent survey showed that 44 percent of our community are on Medicare or Medicaid. Hospitals would have little incentive to continue to provide services with such a huge loss of revenue. This would cause a severe access-to-care problem for our community.

Our association and our community have written to HCFA with our concerns. We recently met with HCFA and aides from Senator Hatch's, Senator Kennedy's and Senator Wellstone's offices to discuss our concern. We are asking this committee to hear our concerns and help us change the proposed HCFA plan to cover our extraordinary costs or institute a carve-out for our drug and other drugs such as those for the immune deficiency who would also experience a similar problem.

We have enough problems to deal with as it is with a chronic disease. Presently we are in a shortage state. Our population is on 60 percent allocation. I always get e-mails from the community saying, "I'm newly diagnosed. There's no product available. I'm told I have to wait until somebody dies till I can get our product," which is basically true. Only what they don't realize is there's a long list ahead of them. We need some help here, and I want to thank you for listening and hope you'll consider this for future a future agenda item and help us.

Thank you.

DR. CAPLAN: Julie, do you want to stay there and see if there are any questions?

It does seem a rather drastic drop in the reimbursement level. One might describe it generously as ludicrous.

[Laughter.]

MS. SWANSON: It is.

DR. CAPLAN: I think that's an obvious source of concern to the community, and this committee has to take seriously things that impede access for people who are on blood products. So I thank you for your input on that.

MS. SWANSON: It's already being affected. People are already having trouble getting treatments in hospitals and physicians' offices. Physicians' offices aren't a good setting for us. We get exposed to a lot of sick people, and they don't want to deal with us because it takes up two hours of their treatment room.

Thank you.

DR. CAPLAN: The Hemophilia Federation?

MR. VOGEL: Rich Vogel, vice president, Hemophilia Federation.

I am very concerned about presentations that we heard here this afternoon, especially from the American Red Cross and the last comment by ABC. It seems that we're headed back to a time where we sacrificed safety for profit, returning to a time when it's quantity not quality that we're looking for. It's that same gift of life that took mine away, because that same lack of concern for the deferral system that we have that they are trying to get in place that I became HIV infected in the early '80s as well as Hepatitis C.

That's all. I just hope--

DR. CAPLAN: Thank you. Any other public comment?

[No response.]

MR. SHERLOCK: All right. One idea that I had about what we might do just for the remaining "two minutes" today is to try to absorb some of the information we picked up about supply issues, availability issues, the issues around reimbursement, the issues around the preservation of safety, is that I think it might be important for us, if we want to do so, to try and come up with a comment or a statement--I'm suggesting this, we don't have to--that says that we are facing the problem and it's important to start to begin to develop strategies to deal with it. That is to say, I don't think it is irrelevant for us to say that there could be a supply problem, is one now, could grow worse soon, and that strategies for trying to wrestle with this are appropriate for the Department and its agencies to deal with.

I'm not sure there's been such a statement. If we say it that way, we'll get attention, because we'll be saying something is broken, might get even in worse shape. So one notion that I had is that we might move toward some discussion of the wisdom of that, is that the time to say that?, is there any value in making a comment? Then obviously that opens the door for us to talk about some of the strategies and steps that Government might take, that the private sector might take to prevent worsening of the problem.

I think we don't have to settle this this afternoon, but I wanted to put on the table the idea that we are a group that can flag a problem, and while we presumed it, I'm not sure I've seen anybody say, publicly, that there is one. I mean, blood groups have come in, the Red Cross, and America's blood banks, and so on, have told us that there's a problem.

But I guess as Jim pointed out, they're always saying that. So there's a shortage. But if this is a more real situation, with more real supply issues facing us, that's an issue.

I think that there are, as I think about this, some other things we could be deliberating about, whether we want to see more funding for some of the behavioral strategies, advertising and recruitment strategies. When I talk about things we can recommend, we may be able to get support for that.

Obviously, people are concerned about reimbursement and payment within the system. I will inject a personal note. We have to be very, very careful about trying to make a call for a reimbursement increase. The whole health care system is tottering around as it tries to absorb cost containment. There's going to be a whole lot of people yelling about not having enough money. This is just one more. Without a very effective case presented about why this area is more vulnerable, or about what the true costs are, about what would be given up, my personal view is it's hard to get heard these days.

I come down the street, I was at Georgetown University Medical Center, I can't remember what the deficit was over there that they were trying to wrestle with, but it was bigger than I could figure. It was, as Everett Dirksen said, "real money." It was like a million a week, a million a week, and then it to somewhere. So I went and gave a speech in Michigan, and the community hospital there were $120 million in unpaid bills in the Southeast Michigan area in the past six months.

So there's plenty of people screeching for money, and just to come out and say, well, you've got to put money into blood and blood safety is not going to do it. It won't do it. There's going to have to be a more effective case than that. That's just my hunch in the political reality of where the battle is going to be there.

And my last comment is, in addition to thinking about resource strategies, I think it is fair game for us to do a little on-the-box thinking. If we're worried that we don't have the most efficient set-up for collecting blood, or if we think that our questionnaires are not doing the job in terms of--and deferral to produce the safety that we think they need, we don't have to solve it in this committee but we can certainly flag attention to getting it fixed, and even as Steve sometimes, and I talk about, if the DRG isn't computed right, we, again, don't have to put on our green eyeshades and compute it, but we'd be ready to say something about a specific area that might need attention by other agencies and officials more appropriate.

So if we're wrestling with supply, one idea I have is: So what's the problem? Is there a problem? Do we want to say there's a problem that would trigger certain steps that the committee has to be persuaded what the problem is? And then recommendations not so much to just say--and if we throw money in it, we'll fix it. I don't think that will warm up anybody in a resolution of what these problems are.

We're going to have to be pretty specific about research strategies, reimbursement, areas that need a closer look, a pretty tight set of recommendations if we're going to really deal with this. This is a tough one. It's a tough one because we've got a system that's pulling through the Medicare Balanced Budget Act about--I think it was $4 billion back, just this year alone, out of the system. So it's a system that's contracting all over the place, and blood will be expected to carry its share, unless we make a case as to why that's not such a prudent thing to do. It won't matter that we say we're hurting, because everybody will say we are too.

DR. AUBUCHON: I would like to provide that it would be disingenuous for this committee or for Congress, or the Federal Government, to imply that we can continue to do more with less, and to close our eyes to the consequences, particularly after Congress and this committee have delivered to the nation a Hepatitis C look-back, which is good, and other arms of the Federal Government have supported such actions as P-24 HIV antigen testing, or now, nucleic acid testing, all of which have very large, substantial costs attached.

Yes, there are other parts of medicine that would like to have additional resources to spend. That's true. The public has identified the blood supply and its safety as being of paramount importance, and possibly the public's attention to this is not rationale. They are spending maybe too much time looking at an incredibly small risk. But that's what the public is telling us that they want, and as a blood bank physician, I'm more than happy to give them that.

I'm more than happy to do all of this testing, to defer donors who might have any kind of risk that would endanger a patient.

I would love to add leukocyte reduction. Maybe it's going to be helpful; maybe it's not. I don't really know, scientifically. But I would be happy to do anything that might improve the safety of the blood supply. But I have to have the resources to do that.

The cost that a hospital has to pay for blood components is very visible. It's very large. One single line-item amounts to somewhere between 2 and 4 percent of a hospital's entire budget. So it's very identifiable to the hospital administrator.

DR. CAPLAN: What's that number?

DR. AUBUCHON: Approximately 2 to 4 percent of a hospital's total operating expenses are related to procurement of blood components, and therefore any increase such as for the cost of leukocyte reduction filters is a big expense for a hospital.

We have to have either overwhelming scientific justification to bring in an expensive new intervention, or we have to have the resources that are commensurate with the public's interest in that, and that's where I've seen the disconnect in the last decade.

The public says we want more safety but we aren't going to pay for it. Yes, the individual patient says, well, I'll pay more for that. But the individual patient never pays for it. It's always paid corporately, really corporately through their health insurance, or corporately through the nation's, the health care reimbursement system. I do think that we need to fix that disconnect, so that those of us that would like to do more have the resources to do it, just as the public wants us to do.

DR. GOMPERTS: Having sat through a number of presentations, hearing a lot of information today, I have some uncertainties. One of the uncertainties is that if the pressures are rising and there are blood centers that are going into the red, is there the potential for quality issues to arise? What is the status of qualified technologists? The turnover rate, the education, the recruitment, the retention of these qualified people.

One particular set of data that I would like to hear more about was that presented by Marian Sullivan where it was mentioned that there are a number of surgeries that were cancelled, a number of requests for patients to receive blood or blood components, that could not be delivered.

The question that I have around that is what were the consequences around that? Were patients actually harmed in that situation?

In those particular circumstances, what could have been done to prevent those situations, whether it was just the availability of blood or perhaps a misallocation of resources or whatever, around those particular situations.

Because if, indeed, if those curves are approaching each other, it may well be that we're right on the edge of a really substantial issue and it's not quite clear to me that this is the case, but there are some questions that I think we should have answers to . We need some more information.

DR. CAPLAN: Let me just say, just listening to the last two comments, again, this is not--I don't want Mack or anybody to jump to their overheads yet--but if you look at what the problem is, you might say--I hear some comment about this and it was in Dr. Satcher's remarks to us, actually, when he started us off this morning and talked about prevention, talked about the impact of financial changes on safety and availability, and talked a little bit about the reserve capacity.

One might say the problem has four parts, at least. One is indications that the supply is in trouble and could be in more trouble. It's a supply issue that's been flagged. The problems of the cost of insuring the safety that people want seem to be burdensome now. So that you want safety but there's a cost.

Financial and reimbursement aspects seem to be risky access. That's even $70 to go to your, get your infusion that costs a thousand, type problem. Then looking forward to prevent future problems with an aging population and different changes in the ratio.

So you might say, just doing a quick summary, we've got--what is the problem? Well, there's supply issues, there's the cost of insuring safety standards, access, and then looking forward, trying to make sure we don't wind up without a reserve and in worse straits, given how demographics and technology costs are going to take us.

So what I said, laying out what the problem is, I meant trying to flag those things as part of a statement. Then it tells us to start to look in different areas of the sort that Ed started to explore, about what some of the strategies might be to solve them.

I'll just say this is my personal view. Personally, I think we'd be well-served if we got a clear statement of what we thought the problems were, because that will let people start to sort of fold strategies out. The same answers aren't the same for every problem. That's what it is. We know there's a problem here, but we'd better say what it is. That'll make some attention possible in the agencies, and so on, if we get the dimensions, according to what we think they are, based on what we've heard today and what we hear tomorrow.

MS. SECUNDY: I wanted to follow up on what you were saying regarding Dr. Sullivan's presentation also, because I think in addition to that information we also need demographic information that speaks to which hospitals and which patients, by class, gender, and race, and in that regard also, I have never seen a breakdown--and it probably exists--for the donor pool, in terms of class, gender and race. Because certainly in the organ transplantation issue, we have had to face questions and problems regarding the number of ethnic American donors vis-a-vis the need, and we might get on top of that early, before we are faced with questions about that as well.

DR. CAPLAN: John.

DR. PENNER: I'd like to comment on cost and supply. In 1945, a new Ford cost about $2,000. It now costs about $20,000. But is it the same car? Or has it changed? What I'm making a point of is we have a totally new product. The new car has air bags, it has all kinds of gadgets, devices, and so on. So we have something entirely different than what we had purchased back in 1950. I think the blood product that we have now is a far cry from what it was even 15 years ago, and we have to accept that fact, and I think we have to be able to consider paying for it.

On the supply issue, you asked what the problem is, and I think the problem is the FDA.

[Laughter.]

DR. PENNER: The FDA has decided that this is the--and with that, I will quickly leave!

[Laughter.]

DR. PENNER: The problem is the FDA because it has considered this is a blood industry, and I defy you to really call it an industry. We have areas that do fit that complexion of an industry, which is the procurement--not the procurement, but necessarily how we fashion it, and send it out, and some of the packaging.

But, on the other hand, the procurement is not the same. We are not being able to purchase the product raw from the minefields of South Africa or wherever. This is entirely as we've gone into this, in depth, as a volunteer donor situation, and it does not confine itself to centralization as has been necessary if you want to apply the industrial standards.

So in doing so, it's been very beneficial in being able to clean up some of the problems we've dealt with that are associated with the viral activities, but we've also lost track of the fact that the population where we're drawing the blood from, the product itself, have been lost, and I think they've been lost because we've lost a lot of the community interaction that was part of developing this willingness to volunteer the blood.

We now have individuals not knowing where the blood is going, who they're giving it to. We have boards of directors, and I can't say this for all, but remembering the Red Cross-the board of directors were people picked in the community who had a great deal of say, and got behind everything.

But suddenly they were eliminated from the loop in that they had nothing more than an advisory capacity. They were no longer being made responsible for the blood product in the volunteers, and as part of that we lost some of the people who were the major people from industry and elsewhere, who would come in and back up the program, because certainly this was not worth their time and effort, to sit and hear somebody tell them about this problem or that problem, and have no say in the matter whatsoever.

So I think we lost a lot of community there, and I think this is bearing fruit in the fact that it's very hard to stir people up to come in on a regular basis because we aren't having that support out in the community. The community leaders are no longer behind it because they consider this kind of a global industrial program and they don't really have an interest in it. So there!

DR. CAPLAN: I'm tempted to--

[Laughter.]

DR. CAPLAN: --further accused of destroying all community values and--

[Laughter.]

DR. FEIGAL: There's many things we're proud to be blamed for having done. I think part of the process that improved the quality of the blood supply is one of the things we happily stand accused of being guilty of, and, you know, having been born in a hospital that was run by a church, with many of the employees in that hospital being volunteers in a small community, where now that hospital is owned by a national corporation, there's many ways that medical care has lost its community feeling, and some of it involves FDA and some of it involves the commercial pressures and the way things are involved.

I think, Dr. Penner, you raise a very good point, because I think a lot of transfusion services never really though they were manufacturers, never really thought that they had something that was a product, was something that they had responsibility to live up to medical products.

But in fact the tradition of regulating things that are produced in biological systems, some of which began as serums and toxins, goes all the way back to the original enactment of the PHS Act, in order to save serum and toxin acts, around the turn of the century.

I take some of your points, but I think that the real challenge is, as I think about it, and having been on the drug side before I came to the biologic side, there's a modernization that's occurred with the drug manufacturing industry that's occurred over the years, and drugs are much better manufactured than they've ever been.

But I think it's unusual for a finished product to have to change, year by year, add testings, new specifications, new standards. I mean, typically, a small chemical entity, a drug--the manufacturer is one of the smallest parts of the cost. It's often said that the average is only about 1/40th of what's charged for it and what it's carrying is all of the research and promotion and development of all the products that never make it to market, and a whole variety of things.

None of that happens with--well, the economics is just very, very complicated, and I think that's partly why we've been very silent. Because the other strange thing about FDA--it's also true of the British system--is that we're asked not to consider cost at all. That's why this committee is so useful, is because this committee has been asked to deal with that, and to deal with the parts of the Public Health Service like HCFA, URSA, AKBR, that consider cost and policy, and policy, and it's a complicated problem, I think, without easy solutions.

DR. DAVEY: Art, back to your questions that you framed, I wonder whether we could frame one a little bit differently, when you ask, Is there a problem? I look at our discussions today as king of having a snapshot on the blood supply. We've focused a lot on safety in this committee and that's our major priority.

We've gone so far on safety that we have a wonderfully safe blood supply. So it's a snapshot on supply. We're muddling by. I mean, we're getting by today. Nobody is really going desperately without blood, although I was impressed with Marian's figures about how many hospitals had to cancel surgeries.

But we're on the edge of a problem and when we make measures that increase--or perhaps increase safety, maybe theoretically increase safety, there's a price to pay, and for an example, the CJD withdrawals, to take an example in the past. They were done with an interest in improving safety for a theoretical benefit, but they had a major impact on doing research in that area.

So these issues we have, when we look at safety issues, have impact on supply and on other things we can be doing in the profession. So we're getting by, I think, but we have a problem coming down the line.

DR. EPSTEIN: Well, one of the funny things that has struck me throughout the day is that although the economics of blood are an important issue related to the donor base, the linkage between how the economic forces are playing out and the forces of supply, are really not that tight, and that as you get into talking about the supply issue, you're really talking about behavioral issues and incentives to donors, and donor psychology, and recruitment strategies.

Whereas the economic issues have more to do with certainly the health of the system, the ability of the institutions to survive, and what kind of institutions we're going to have, and what kind of relationship that they have to the public.

So I guess one point that I would make is that I agree with you, Art, that there ares a set of discrete issues, and, in my mind, they're really not that well-connected, or at least at this point in time we don't understand the connections. That's my first point.

My second point is that I think what we've accomplished today is we've had a very good effort to dissect the issues. We saw that the economic issues have a couple of comment themes. There's the issue of the competitive forces and how they're changing the landscape.

There's the issue of the rising cost of producing products, the relationship of that to safety initiatives, and the adverse impact of cost containment on trying to bring forward those initiatives, and then we've seen the whole issue of managed care and reimbursement. The impact of managed care on sort of holding back progress, and the issue of reimbursement on what you called the access problem.

With respect to the donor base, I think we've heard a different set of issues. We've heard that there are negative impacts of precautionary policies that are resulting in large percents of donor deferral usually because of some level of nonspecificity about what that measure is.

In other words, its yield is low, or its specificity is low, but it's costly in terms of donors, and dollars.

But we've also heard that there's a changing donor base, that you know, you have an aging population, you have possibly a different spectrum of, you know, civic-mindedness in the different age groups, that the risks attacked to these population subsets aren't the same, and that the recruitment strategies won't work in the same population subsets, automatically. You really have to stratify those approaches.

I guess one issue that I heard that somewhat cross-cuts these two is the whole matter of regionalization versus nationalism. The nationalism related to the economic issue is about price wars, and it's about underbidding, and it's about eliminating local service, and the concept of the local provider as a service provider, which I think is what's bothering Dr. Penner.

But at the same time, the loss of the sense of regionalism is related to the donor base issue because everybody understands that people like to donate for their friends and neighbors. When they can see the value of it, locally, they understand it and there's a motivation there.

I'm not sure you can instill a national motivation, but certainly it operates easier when it's seen locally. So I guess that the point that I'm making is that I think that those two broad issue areas have not been well-connected, although I'm not sure connections don't exist, but that we have succeeded, I think, in developing some of the forces that need to be examined in each of those areas to make a better system, whatever the goals of a better system may be.

I guess that I was just struck by Harvey Klein's remarks, at the very beginning of the day, that perhaps the goals and objectives of the national blood policy remain the primary issues that are relevant today.

DR. CAPLAN: I can make just two comments on what Jay said about making a connection. One small tight one that comes from the world organ donation that Marian was talking about. When we've done surveys at Penn, in my group of organ and tissue donor behavior, it becomes very clear that one reason poor people don't want to donate is they don't think they have access to the service.

I don't know if that's true in blood, but it's definitely true in organ donation. If you go out to the community and say how'd you like to donate your liver when you're dead? and the person saying, "But you wouldn't give me one, if I needed one," it tends to dry up their altruism. So access, in terms of how the system is financed, can drive donor psychology, and, in a broader way, if people see medicine or health care as a marketplace commodity, it's very tough to appeal to their sense of good will to support it.

So if your image of health care becomes a large managed care organization, or somebody earning a lot of money, as the CEO of a company, it's a different thing than going down in a little hospital in the community and saying, well, that's the thing I want to support.

So I think they're there. Jane or other social scientists could do better saying whether these things actually get linked in anybody's head as they think about stuff, but I think there are connections, but they're of that--sort of donating, or being an altruist to a marketplace, or a commodity, or a big business, is a tricky thing. And I know it's true in organ donation. I've seen that time and again. It's the unstated premise.

If you can't get it, you don't want to give it, and if they think the system leaves--if people think they're left out or can't get access, they really aren't going to play ball to opt in on a altruistic basis.

DR. EPSTEIN: I think you're right, Art, but you're back in the psychological domain. In other words, if HCFA let blood collection establishments pass through their collection costs, you wouldn't, therefore, in any automatic way, have a more elastic donor base.

DR. CAPLAN: True. That's true.

DR. WALSH: Art, thinking a little bit out of the box but in the freezer box, if you will, I'd like to ask if we could have Captain Rutherford just kind of review the DOD experience in optimizing utilization of limited resources. They seem to have done a good job for quite a long time, and I wondered if you'd care to elaborate.

CAPTAIN RUTHERFORD: That's being put on the "hot spot," isn't it? Well, I guess most of you know DOD has had a long experience with frozen red cells, dating back to Dr. Robert Valeri in Vietnam. In fact at this moment we have probably around 56,000 units of frozen red cells pre-positioned throughout the world and quite a number on some of our naval vessels, especially those that are primary casualty receiving vessels, and the two hospital ships.

As a blood banker in San Diego in 1980, I used frozen red cells quite extensively to manage my inventory. We only froze O pos and O neg. When we had overages we would freeze, and so it was just like regular banking. If you got your paycheck and you have more, you put some in savings.

So we were always freezing, knowing that we would have days when we could manage our inventories, and we didn't use them for emergencies because we couldn't degliss fast enough. You cannot degliss fast enough for really large emergencies.

But we were able to manage our inventories quite effectively by deglisserizing red cells for our cancer patients, and patients that we knew were going to be transfused, and the physicians could wait two or three hours until we got enough units deglisserized to give to them.

Frankly, frozen red cells, for us, were safer than liquid red cells because the donor never came back as a tested donor of an infectious disease. So we felt like that donor was a little bit safer.

We didn't have to worry about white cells or platelets clogging up the filters or causing problems in the lungs, and it was a clean product, and all the plasma was washed out. So we felt like it was a much better product.

So, I mean, it does have a cost to it. You have to invest in minus, you know, 65 degree freezers, deglissing machines, so there are costs associated with that, but it is an effective tool for managing, and I'll have probably more to say tomorrow on the hemoglobin-based oxygen carriers, and fibrin bandages and frozen platelets.

DR. AUBUCHON: Art, could I offer, not in opposition to what Captain Rutherford has said, but just to give a civilian hospital perspective on blood management, lest the committee think that if we were freezing red cells, all these problems would go away.

To begin with, there are almost never any excesses of group O red cells. This is the most frequently used group, and if a group O red cell is heading toward outdate, it can be used, obviously, for any other group recipient.

So we don't have excess, we don't have outdating in group O's. What we have is outdating in group ABs and A's. ABs can only be used for ABs, and about half to two-thirds of all red cells that are outdated in the United States, outside the military anyway, are AB.

We could freeze them, we could store them for the next millennia, and they would still be sitting in the freezer.

The next problem comes to logistics and that is that the military, operating relatively large facilities, can have the frozen storage and deglissing capabilities in the same facility where the transfusions take place.

It doesn't work so well when you have small hospitals distributed across the countryside and these hospitals do not have the wherewithal to do the deglissing. Coupled with the fact that once the unit has been deglissed, currently available technology, it has a 24-hour outdate. So you have to know that you're going to use this unit when you thaw it out; otherwise it will indeed outdate.

Finally, we come to cost, and possibly that's not quite as much a problem for the Department of Defense but for a civilian hospital, the cost of a frozen and then thawed unit is approximately two to four times of a liquid stored unit.

So that also would not be a viable reason to go in that direction.

DR. CAPLAN: You look like you wanted to say something.

CAPT RUTHERFORD: No. I mean, I agree with some of the things he says. I mean, you can sneak four or five of red Group O out, and you can freeze them without too much of a problem. So if you truly want to develop a frozen blood program you can. We are working on a deglycerolization machine that is almost to the point of being tested, where it will sterilely glycerolize the units as well as act as a deglycerolizing machine that is sterile and by adding an already FDA-approved solution to it, such as Nutracell, we can probably get three weeks of storage on those red cells, also. So we are working on that problem, also, as far as research goes.

DR. HOOTS: I wanted to ask both Jim and you, I am sure what you said is true, Jim, because obviously that is representative of the demography of the U.S., but if for a moment, just thinking out of the box and in the context of what the DoD does, and if we were going to try to produce our own underground oil reserves like we did during the Arab oil embargo, for blood, if we could improve recruitment strategies in ethnic groups that have a high prevalence of O, for instance, and incentives them in an ethical sort of way, since they are probably not donating at a large frequency anyway, or at least based on the data we saw today.

Perhaps that might be at least a national resource that could be drawn on if we got into a real, real pinch. It wouldn't solve your day-to-day problems, but it might actually if, in some of the really bad flux times, supply, you know, if we got into a real, real severe shortage. I don't know, I just raise the issue.

DR. CAPLAN: Like those salt domes in Louisiana.

DR. HOOTS: That's right.

CAPT RUTHERFORD: Let me give you a little background perspective from the DoD. We got into frozen red blood cells simply because there was no other thing out there that we could preposition. And this strategy was developed back in 1986 when we realized with the Medical Red and the strategic plan that we needed over 225,000 units of frozen red cells in the Pacific, mainly on the Korean peninsula and throughout Europe. That was before the fall of the Iron Curtain.

So we have always looked at frozen red cells as an interim solution. We knew that some day research would follow up, and we would get something else, and we were putting all of our eggs in a basket when it came to hemoglobin-based oxygen carriers, and we still believe that. Once a hemoglobin-based oxygen carrier is licensed, we hope it's licensed, and we get the different clinical outcomes that we think we're seeing now and the different treatments in patients that can be treated with that and the trauma trials do look good, that we will probably phase out our frozen red cells, and we will be able to preposition hemoglobin-based oxygen carriers in much more larger quantities and definitely on ships that we can't even do frozen red cells on right now.

DR. CAPLAN: So as soon as the licensure takes place, Jim should put in for the fire sale on deglycerine machines.

CAPT RUTHERFORD: And we have plenty.

DR. CAPLAN: Scatter them all over New Hampshire.

DR. McCURDY: I think, if I remember correctly, there are at least three, and maybe only three, civilian hospitals who made an effort at one time or another to run a completely frozen blood program. Two of the three, I understand, have abandoned the program. I think both of them abandoned it when the proponent laughter retired or something about that.

The third one I don't know so much about the current status, but I do know that it was a hospital that used about 10 percent of the collections of a major blood center. They used about 50 to 60 percent Group 0 and put a very serious stress on the system, as far as other hospitals were concerned, by that attempt to conserve their ability to use Group 0. They also had a trauma center, so it wasn't all in the deglyc program, but a large portion of it was in the deglyc program. I think trying to move that into the civilian area and trying to get enough Group O's that you could freeze would stress the system considerably more than it's being stressed now.

MS. O'CONNOR: This has nothing to do with freezing blood. But this morning Dr. Satcher talked about having enough resources for health, but just a reallocation of them. And I was certainly struck by the comment of people not being able to get what they need and the extraordinary cost. I don't know if it's part of our committee's job, but can we ask to do an overall assessment of where the funds are going? I mean, Dr. Satcher talked about prevention, and that makes a great deal of sense. But there are people in urgent need now, and we need a way to balance it. I don't feel qualified, and it seems like a huge project. But I would certainly recommend, say that there is a problem in health care, and it needs a big strategy to reallocate the sources.

DR. CAPLAN: We've certainly been flagging access issues for some groups in previous meetings, whether it's IVIG or clotting factor issues and so on. I'll have to think about that in terms of how to phrase it, but I know what you're asking.

DR. NIGHTINGALE: This is Steve Nightingale.

If I could make a procedural comment, we asked you today to examine one question, and you did that and gave us a second one. We asked you to deal with the reserves, and you dealt not only with the reserves, but with the financial issues which we anticipated would be the next meeting of the committee. That was the gist of the prepared portion of Dr. Satcher's statement.

It has been, from the perspective of a person who was trying to obtain, collect and organize a large body of information to present to the decisionmakers, an extraordinarily successful meeting, and I would emphasize that not in our wildest dreams did we expect this committee to solve this complex problem in a single day or even two would be my view. We have another day to go simply to discuss aspects of the reserve capacity of the blood system.

I do plan, certainly, to prepare the material, the vast amount of material that was prepared here in as readable format as I can as quickly as I can. You will get a much more comprehensive summary of it than you have in the past. I think this will require more than eight pages to do justice, and I think it will require more than 10 to 15 minutes of reading those eight pages for many of the members of the committee--I might even say all of us--to digest this information effectively.

In my wildest dreams, we could come up with an initial set of solutions, not solutions, but proposals for action by the end of our next meeting. The hope, in scheduling the meetings as they are scheduled, is that we would still have time to do that. The idea is to anticipate problems rather than to deal with them, and I think I am quoting not only the text, but the sense of what Dr. Satcher was trying to communicate to you in that last statement.

MR. ALLEN: As the day has gone on, we have all heard once again about another potential shortage. I am glad to hear that this shortage isn't on our doorsteps like the blood product shortage was, but we all realize that it sounds like it's coming.

I still have some reservations regarding how we heard about the blood product shortages, and what has been done or not done up to this point. I can't help but feel the same frustrations of a lot of the consumers who are in need of these products are going through, coming to these meetings, hoping to hear something concrete, some kind of a solution, which is why we're here, but they're not hearing that. They are hearing about more meetings, more talk.

I would just like to suggest that we bring together as many of the parties involved as possible. Between the blood industry, the FDA, the CDC, the HMOs, the physicians, we need to do something to expedite some of these issues. They are just going on too long. The people that are in need are still waiting for us to do something about it, and that's not happening yet.

And related to that, one of the issues brought up today was how some of the states, I believe it was ten states mentioned, that are regulating the tissues and the other products that can stay within the region, and I am curious why this wasn't done. We talked about this before about the IVIG shortages, but why can't we do that nationally with some of these shortages now? We've got to take care of our people first. I just think that if the states are able to do that with certain things like organs and tissues, then maybe we should be able to look into how we can do that to deal with these blood-product shortages now, not next year, now.

DR. CAPLAN: One thing that's crossing my mind, too, based on what Larry said and a little bit of what Steve is going out of the box. I mean, the committee has representation from a lot of sectors, but maybe not all needed, and it's not beyond us to convene a summit on where the shortage went or to convene or ask the Secretary to convene a bigger set of folks for a more systematic examination, not just of the immediate shortage in the blood products thing, which we've been trying to wrestle with in various ways, but to try to get on top of the impending shortage on whole blood, on red cells and other blood products as well.

So it may be possible to do what you're talking about by recommending that we need a bigger set of folks at a table; that they have to, perhaps, take a set of points that we present to them and then move them forward. Because as Steve said, we not solve everything here, but we could charge somebody to both check in and say, "So what happened to the production line capacity and where are we with our FDA inspections and so forth and so on. What moved there?" So that is something we could definitely think about.

MR. ALLEN: It's just frustrating because we're not seeing, we're not getting the entire picture here. We're only getting parts, and without the whole sum here, we're not going to get this done.

DR. CAPLAN: Having decided to charge the entire field of health care with paying attention to our recommendations might be a modest note to end on for today.

I think that tomorrow we're going to look at a very concrete phenomena. It's the hemochromatosis issue of putting that blood back into the blood supply. We may decide to say something about that, if not tomorrow, then at some point down the road. And I think we already saw a smidgeon of the fact that we'll get some discussion going on that subject today.

So that's what we'll start off with tomorrow. We will reconvene at 8:00.

Thank you.

[Whereupon, at 5:10 p.m., the proceedings were adjourned to reconvene at 8 a.m., Friday, April 30, 1999.]

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