Blood Safety Transcripts

DEPARTMENT OF HEALTH AND HUMAN SERVICES
ADVISORY COMMITTEE ON BLOOD SAFETY AND AVAILABILITY

Twelfth Meeting

THE ROLE OF VARIOUS CONSIDERATIONS IN DECISION
MAKING RELATED TO NEW AND EXISTING
BLOOD SAFETY MEASURES

8:10 a.m.

Thursday, August 24, 2000

Hyatt Regency Capitol Hill Hotel
400 New Jersey Avenue, N.W.
Washington, D.C. 20001

P A R T I C I P A N T S

Arthur Caplan, Ph.D., Chairman

Stephen D. Nightingale, M.D., Executive Secretary

Larry Allen

James P. AuBuchon, M.D.

Michael P. Busch, M.D., Ph.D.

Mary E. Chamberland, M.D.

Richard J. Davey, M.D.

Jay Epstein, M.D.

Colonel Fitzpatrick

Ronald Gilcher, M.D.

Fernando Guerra, M.D.

Paul F. Haas, Ph.D.

William Hoots, M.D.

Dana Kuhn, Ph.D.

Karen Shoos Lipton, J.D.

Paul R. McCurdy, M.D.

CAPT McMurtry

Gargi Pahuja

John Penner, M.D.

Jane A. Piliavin, Ph.D.

David Satcher, M.D., Ph.D.

John Walsh

Jerry Winkelstein, M.D.

C O N T E N T S

AGENDA ITEM        PAGE

Welcome, Roll Call, Conflict of Interest Announcement        4

Comments by the Assistant Secretary for Health and Surgeon General David Satcher, M.D., Ph.D., Department of Health and Human Services        7

Centers for Disease Control and Prevention Hepatitis C Initiatives, Harold Margolis, M.D., Chief, Hepatitis Branch, CDC        37

Statement of Issue, Stephen Nightingale, M.D., Executive Secretary, Advisory Committee on Blood Safety and Availability        91

Comments by Chairman and Members 99

Comments by Public --

Lunch        191

Committee Discussion and Recommendations --

Adjournment --

P R O C E E D I N G S

DR. NIGHTINGALE: Good morning. My name is Dr. Stephen Nightingale, and this is the 12th meeting of the Advisory Committee on Blood Safety and Availability. Could I begin by calling the roll? Dr. Caplan?

CHAIRMAN CAPLAN: I'm here.

DR. NIGHTINGALE: Mr. Allen is in transit. Dr. AuBuchon

DR. AuBUCHON: Present.

DR. NIGHTINGALE: Dr. Busch?

DR. BUSCH: Present.

DR. NIGHTINGALE: Dr. Chamberland?

DR. CHAMBERLAND: Present.

DR. NIGHTINGALE: Dr. Davey?

DR. DAVEY: Present.

DR. NIGHTINGALE: Dr. Epstein?

DR. EPSTEIN: Here.

DR. NIGHTINGALE: Colonel Fitzpatrick?

COL. FITZPATRICK: Present.

DR. NIGHTINGALE: Dr. Gilcher?

DR. GILCHER: Here.

DR. NIGHTINGALE: Dr. Gomperts is unable to attend today. Dr. Goosby I believe is in transit.

Dr. Guerra?

DR. GUERRA: Here.

DR. NIGHTINGALE: Dr. Haas?

DR. HAAS: Here.

DR. NIGHTINGALE: Dr. Hoots?

DR. HOOTS: Here.

DR. NIGHTINGALE: Dr. Kuhn?

DR. KUHN: Present.

DR. NIGHTINGALE: Ms. Lipton?

MS. LIPTON: Present.

DR. NIGHTINGALE: Dr. McCurdy?

DR. McCURDY: Here.

DR. NIGHTINGALE: Ms. Pahuja?

MS. PAHUJA: Here.

DR. NIGHTINGALE: Dr. Penner?

DR. PENNER: Here.

DR. NIGHTINGALE: Dr. Piliavin?

DR. PILIAVIN: Here.

DR. NIGHTINGALE: Dr. Secundy is unable to attend. CAPT Snyder?

[No response.]

DR. NIGHTINGALE: CAPT Snyder would be in transit. Mr. Walsh?

MR. WALSH: Here.

DR. NIGHTINGALE: And Dr. Winkelstein?

DR. WINKELSTEIN: Here.

DR. NIGHTINGALE: The public service notice regarding conflict of interest that has been read at the beginning of all prior meetings of this Committee is included here by reference and will be read in full after Dr. Satcher's and Dr. Margolis' comments.

Dr. Caplan will introduce Dr. Satcher.

CHAIRMAN CAPLAN: I'm very pleased that the Surgeon General is here with us again. We have been wrestling for some time with a variety of issues, and as I think he knows, today's meeting has more of an open agenda than we've had in the past in terms of trying to respond to requests by him and the Department. We're going to touch upon a number of topics that this group has wrestled with in the past, and I suspect members of the Committee may bring up a few others maybe that are brewing as we go along.

But I know he's going to comment to us about a few of the issues that we have been wrestling with and bring us up to date. So let me turn the floor over to the doctor.

DR. SATCHER: Thank you very much. I'm again delighted to be able to join you at least briefly--I'm sorry. Thank you. I'm delighted again to be able to join you, if only briefly, to again express our appreciation for the outstanding work that you continue to do and also to help try to put in perspective how we see the challenges and certainly the significance of today's meeting.

This summer, in response to your request, our office prepared summaries of both the origin of this Advisory Committee and your accomplishments to date, and I think all of you have now received the formal summary as of June 12th, probably, and the latter summary you should have received by now. I think it was sent out on August 4th.

There are six broad areas which you have addressed in a very productive fashion: hepatitis C lookback, the issue of the transmissible spongiform encephalopathies, the shortage of plasma derivatives, the shortage of blood products, reimbursement for blood products and plasma derivatives, and the management of error in transfusion medicine.

In each of these areas, I think we've made substantial progress, and we want to thank you for your contributions. But as you know, there are many challenges which remain, and now is certainly not a time to relax our vigilance or lessen our efforts when it comes to assuring the safety and availability of the blood supply.

Let me take a minute to review our progress with the hepatitis C lookback, which was the first major issue. A guidance to the industry that incorporated your January 1999 recommendation was published by FDA on June 17, 1999. A proposed rule based on this guidance has been prepared by the Department, and it is presently awaiting final review by the Office of Management and Budget. And I think you're probably familiar with that process. The target date for completion of direct notification is September 30, 2001.

We've received assurances from the blood industry that direct notification will be completed within that time frame, and we have reviewed assurances from the Commissioner--we have received and reviewed assurances from the Commissioner of FDA that her agency is prepared to monitor compliance with this process.

Our general notification program for hepatitis C is also underway, and Dr. Alter provided you with an update on this program last January, and today I understand Dr. Margolis will provide you with an additional program update, in fact, in just a few minutes, and this is very important.

But I do want to mention something else. In January of 1998, when the Secretary announced the initiation of the hepatitis C lookback efforts, she acknowledged your first set of recommendations on this subject, but she also said something else which I want to remind you of. She said, "I intend to go even beyond your recommendations. I consider these steps to be only the first phase of a comprehensive plan to address this significant public health problem. So it is my intention to reach effectively as many people at risk as we can. Today's decision," she said, "will allow us to move immediately to address concerns among transfusion recipients at greatest risk. At the same time we will educate the public at large, evaluate our efforts, and take even more steps to address unmet needs as we identify them."

And this is what we have tried to do with the hepatitis C lookback. This is the same approach we've taken to the other challenges, I think, to blood safety and availability that we've encountered, and we hope to continue to do so.

But I do want to mention the latest effort in this regard because we have had discussions about sending a letter from the Surgeon General to every household in America about hepatitis C because of the magnitude of this silent epidemic affecting four million people. And the struggle, of course, has been that there's only one model for doing that, I guess, in the past and that was when Surgeon General C. Everett Koop sent a letter about the HIV/AIDS epidemic.

There have been some major changes since that time. At that time the Surgeon General's office had what we call franking privileges, and there was no problem in sending mail to all of the families in America. Congress has long since withdrawn that, and now only Congress has such privileges, so it would cost us between $30 and $40 million to send such a letter.

However, in discussions with leaders in Congress, especially Congressmen Bliley and Coburn and Brown and some others, we agreed that we would take advantage of the franking privilege of the Congress to send the letter. So on July 27th, we held a press conference with members of Congress and announced that, in fact, a letter from the Surgeon General would be sent to all the constituents through congressional mail. And so we have moved forward with that in terms of putting together a letter, and the Congressmen have sent letters to all of their colleagues urging them to transmit this letter.

There are a couple of things that we have to deal with. One has to do with the separation of the different branches of government and to make sure that the letter is written in such a way that it doesn't imply any breach of that separation. So we'll be changing a sentence here or there from what you received, especially the one that says, "We have joined with the Congress." We're going to say that differently.

[Laughter.]

DR. SATCHER: So nobody will misunderstand what we're saying.

The other issue, which I think is a very important one, is we are sending letters to all of the households, hopefully, and we hope that it will get the desired response. Now, if you ask me if we're prepared to deal with the desired response, that raises another issue that we should be aware of, and that is that there are not adequate federal funds to support the state and local level programs to respond if people will, in fact, as we would like for them to do, if everybody would come seeking testing and treatment as indicated. But I think that's a good problem to have in the sense that--the good problem, of course, is that we have put the problem in perspective by sending this letter, and hopefully it will lead us to move forward to make the resources available to deal with this issue. We want to deal with it. So that's sort of where we are there.

Today I understand that one of the things you're going to be discussing is the role of various considerations in decision making related to new and existing blood safety measures, or I guess to answer the question: What are the principles on which a policy to assure a safe, available, and affordable blood supply should be based?

So we certainly look forward to the outcomes of this meeting, but I also want, before in conclude, to express our appreciation to those members of the Committee whose terms are expiring. I want to thank Mr. Allen, Dr. AuBuchon, Dr. Gomperts, Dr. Penner, and Dr. Secundy for your contributions to the Advisory Committee during your three-year term, which ends, I guess, on September 30th of this year. But we certainly want to assure you and to assure those who are not here that they have not seen the last request for public service, and we hope that they will be as generous with their talents in the future as certainly they have been as members of this Committee.

Now, one final comment. In addition to advising us on blood safety, I want you to know where all of this fits into the bigger picture of Healthy People 2010, the nation's health plan for the next ten years. And I think we released that plan on the day when the government was closed down, and we were having this national meeting, and you met and I remember coming here to meet with you. But we did something for Healthy People 2010 that we've never done before in Healthy People. We have now over 400 objectives. We felt that there needed to be a national strategy based on easily definable and a set of indicators that we could easily communicate to the American people. So we came up, with the help of the Institute of Medicine, with leading health indicators, and that's what you have at your desk. You have a bookmark of the leading health indicators.

It's interesting. Five of them we say are lifestyle and five are health system indicators. And what we hope to do over the next ten years is use them as we use leading economic indicators. We want to monitor the progress, and we have measurable objectives on each one of these indicators. And we hope to monitor the progress of the nation toward reaching these measurable objectives.

Now, I won't go any further than that except to say you might want to take any problem that you're concerned with and ask yourself how these indicators would impact upon that. I did that last week with cancer, and you might want to just go through and say if your concern is reducing mortality from cancer in this country, how would each one of these indicators relate to that? I think you'll be surprised to find that virtually every one of them has an impact on the risk for cancer.

I want you to know that because I want you to help us also with the whole issue of Healthy People 2010 and moving this nation forward to meet those goals and objectives.

Thank you very much.

CHAIRMAN CAPLAN: Do you have a minute for some questions?

DR. SATCHER: Sure.

CHAIRMAN CAPLAN: Okay. Why don't I open the floor for questions, comments. Dana?

DR. KUHN: Dr. Satcher, I want to just thank you and the CDC for the efforts you put through in putting--in this "Dear Citizen" letter. I think it is much timely and much needed, given the fact of how long we've been dealing with the issue of hepatitis C.

But two questions I wanted to ask you, because I think what I'm hearing you say is there's a little concern about how Congress has withdrawn the franking privileges of the Surgeon General. Is anything being done to reinstate the franking privileges? And then, second, is anything being done to request funding perhaps in this next budget so that this letter can go out to the citizenship of the United States?

DR. SATCHER: Well, the letter is going out. It's going out through the good graces or the support of Congress. So that part is taken care of. They have made a commitment to send this letter to their constituents. So it does raise the next question that you raise. What will be the impact of this letter and will we be prepared to deal with it?

If we receive the maximum impact, it would stress, severely stress the system as it now exists and really bring into sort of bold perspective the fact that perhaps there's not adequate support for the state programs in this area. We know that already. However, we don't know how many people will need--how many people will have insurance coverage and things like that as they seek to respond, how many people will go to the public system.

We could envision a situation where the "public system" was, if not overwhelmed, severely stressed. And we're aware of that, and we hope that Congress will continue to increase funding in this area.

But certainly I can tell you that the Association of State and Territorial Health Offices are concerned about being able to respond properly.

CHAIRMAN CAPLAN: Jane?

DR. PILIAVIN: Your talking about how the letter is actually going out to all the households makes me think in terms of our unhoused people. Is there going to be any way of trying to reach them? Clearly, many of those people have substance abuse problems, and almost none of them have access to medical care.

DR. SATCHER: That's a general problem that we have with all of our programs, and I can only say there are different levels of programs in different communities throughout the country now dealing with that.

You know, one of the best examples of that has been, I have to recall, dealing with tuberculosis, when we had the dramatic rise in tuberculosis from '85 to '92, almost a 7 to 10 percent increase a year. What we discovered was that much of that problem was in the population of homeless people in this country, so we had to develop strategies, including directives of therapy, to reach them.

So there are strategies that can deal with this issue, and CDC certainly is always looking for new strategies, and maybe Dr. Margolis will comment on that. But, yes, we are concerned about that population, and jails and prisons, homeless, those are major challenges for our public health system. And it really raises the bigger issue: To what extent is our public health system now relevant to a population in which so many people are in our jails and prisons? For example, I believe the rate of HIV infection in jails and prisons is like eight times what it is in the rest of the population. So any public health system that does not respond to that and which people are--the jails and prisons are part of the community. People go in and out, in and out. So whatever goes on there is actually a part of the general community, whether we like it or not. And, therefore, increasingly our public health system must include how we deal with the jails and prisons.

We're trying to deal with that. As you know, my Deputy Surgeon General, Dr. Ken Moritsugu, before he became Deputy Surgeon General, was Medical Director of the Bureau of Prisons. So we have improved our working relationship. CDC has some targeted programs both for the homeless and for people in jails and prisons, working very closely with the correctional institutions. So we are going to be sending a letter.

I didn't respond to your point about franking, and I can't. You know, it's a tough issue. Congress made this decision, and I guess there has even been a ban on using the franking privileges now for a period of time.

DR. NIGHTINGALE: We discovered that you cannot send franked mail within 90 days of an election. When we had the press conference on the 27th, it was the impression of both the executive and the legislative staffs that that ban was 60 days. A lot of work has gone into this so far, and obviously a lot of work remains to go into it. The commitment is to do the work.

DR. SATCHER: But there are a lot of things--to get back to your basic question, there were a lot of things that happened to the Office of the Surgeon General during the last four years, between '94 and '98, in terms of reduction in budget and things like that that have been a problem for us. We have found ways to compensate for them in many cases to get reports done and to get them out. But it's not because of the resources in that office. It's because we have managed to use the agency resources, and they have been great in providing them and responding to requests to get things like the mental health report and the oral health report and the tobacco report done, not because of money in our office but because we have been able to work with other people, and now working with Congress directly in getting this letter out.

I took a deep breath on that one.

DR. GUERRA: Dr. Satcher, again, thank you very much for making the time to join this Committee at our meetings.

You commented about the public health responsibility and certainly the increasing demands on a system that has not always had in place the kind of structure and support that is very much needed. And certainly one of the very important considerations relates to the identification of individuals that have infection with hepatitis C virus and that are progressing with their illness and that obviously need a variety of interventions for more clearly defining the status of their disease and hopefully connecting them to some treatment.

But on the public health side of that, we certainly need to make sure that they are protected against hepatitis A and hepatitis B in the instance where they're at risk for those diseases, and also that they have access to detox programs when they're substance users or alcohol-dependent, which obviously is a comorbidity that puts them at even greater risk.

The resources are not in place to do that. In the instance of my own community, where in a relatively short period of time we presently have over 5,000 individuals in our registry for hepatitis C that we have identified just with some minimal efforts that we have been able to support through our own department for screening and counseling, doing the testing. But we don't always have enough vaccine for the adult population because they're not eligible for the Vaccines for Children Program to protect them against hepatitis A or B, and then also to try to get them into some system of care.

Unfortunately, many of these, as you well know, are within some of the minority communities, for instance, within the Mexican-American or Hispanic and Latino community that has many who are uninsured and/or marginally employed and not eligible for any benefits.

In the instance where they do have some coverage, you know, managed care organizations will not often cover the preventive measures and/or the work-up that needs to be done.

Is there something taking place at the federal level to try to at least put some of that responsibility on those systems that are in place for serving uninsured or in the instance of managed care organizations that they do have an obligation to their patient populations? What is your sense also of the availability of additional vaccine program support for these populations?

DR. SATCHER: Well, let me just say I think we continue to review our relationship certainly with managed care organizations who contract for the care of Medicaid populations, and I think that is going to continue. It is a very serious problem, because we have had cutbacks in several areas in terms of the budget, and as we look at our budget situation today, it is really critical that we look at the areas of need in public health.

Those have been documented very well by, again, the Institute of Medicine's report in 1988 talked about a public health system that is in disarray, and documented the loss of infrastructure, especially at the State and local level. We have been trying very hard to rebuild that infrastructure. We have made some progress, in terms of the State public health laboratories, for example. Most of this progress has come about in response to emerging infectious diseases and the threat of bioterrorism.

We have a long ways to go, as you point out, so we are looking for strategies of public-private partnerships to reach the populations in greatest need. You know, ultimately, obviously, we keep dealing with a system that is, in some ways, well-funded, but not well-organized, in terms of the need for universal access and dealing with the lack of universal access in this country, which is one of the things that led the World Health Organization to rank us so low among the nations of the world. I think we're ranked number 37 in terms of health systems efficiency.

So, part of what we're trying to do is figure out a way to adequately fund the system and then organize it in such a way that it operates most efficiently for everybody. So, the gulf between here and there is still pretty wide. You know that better than I do, because you have been on the front line a long time, and, obviously, our relationship, federal, state, and local, putting together a public health system that is well-coordinated, is one of the real challenges that we face.

CHAIRMAN CAPLAN: Mike?

DR. BUSCH: Yes, Dr. Satcher, I would also like to commend both you and the Public Health Service for the enormous focus and contribution in the area of blood safety. I think today the risk of blood is extraordinarily low, and the progress is really a tribute to the system and to the incredible accomplishments of technology, in applying it to blood safety. I think the discussion over the next day will be how much additional resource can we afford to put into closing that last bit of the window period or adding safety measures, such as leukodepletion, which have marginal safety benefit.

So, we're struggling with the enormous resources that are required to further reduce risk in blood safety. I think there are two related areas, though, where a modest amount of resources could have a high impact. One of the other charges of this committee is the availability of blood, and there remains a serious problem with blood donations.

About half the blood centers in the country now are struggling to collect enough blood, and I know that about a year ago, there was discussion about a public health sort of campaign where yourself and others were going to do television commercials, et cetera. I have not heard much about that. We have seen in Canada an enormous impact through an orchestrated public health campaign to increase blood donations, and I think that is an area where I could imagine Give Blood being added to this list, because I think that giving blood is a process that encourages safe health. The process of going through that interview, understanding risk behaviors, et cetera, could ramify out in terms of broader public health safety implications for individuals as a whole, as well as, obviously, it is a good, you know, general sort of ethical behavior.

So, that is one area I would like you to comment on; the other is the issue of blood safety around the world. We heard, at our last meeting, the reality of developing countries, where I think it is estimated that, in developing countries, perhaps 20-to-30 percent of the blood that is collected is not even screened for basic antibody tests, and that translates into more units of blood than are collected in this country altogether every year, are being transfused without even basic screening.

I will show later that basic screening with simple, inexpensive tests would interdict probably 98 percent of the infectious units. So, I am wondering, I know there was the major focus by yourself and the world on Africa recently. I am wondering if there's any potential that significant U.S. research or resources safety could be put towards bringing forward basic blood measures in developing countries.

DR. SATCHER: Well, let me start at the end, and forgive me if I forget some of the things you have raised, but I think the World Health Organization meeting in November is certainly an opportunity for us to engage in a discussion about the global implications of blood safety, and to also put into perspective how we and the United Nations World Health Organization can best contribute to blood safety worldwide.

So, I think that is what this is all about. That discussion is underway. I believe we had--at the World Health Day, I believe we had a discussion about blood safety. So, we are trying to put that into perspective. Let me just say to you that is a very difficult issue. I have visited the hospitals in Africa. I remember going to a hospital in Kissimu, western Kenya, where the choice between transfusing blood that is not, as we would define it, safe, and saving the life of a child with cerebral malaria is such that, are you going to take the time to go through the process when you know that you have got to give the child the blood? You have got to choose between safety right now and a child that will die within the next week or so, but a child that might well be infected with HIV because of that unit of blood that you have to give anyway because of the situation.

So, we have got to deal with all of the things at the same time, but I believe we can get to the point where we can make the technology available to developing countries. When I led the team to Kenya and Tanzania after the bombing of our embassies, and the whole issue of blood safety was another issue we dealt with there, where again the systems were just not in place. So, hopefully through the United Nations, through the World Health Organization and our participation, that we can begin to bring to bear our technology on blood safety in developing countries.

As far as--Damon, do you want to comment?

MR. THOMPSON: On the PSAs.

DR. SATCHER: Yes. The next issue is what are we doing about getting people to contribute more blood in this country. It is a very important point, because we have had an evolving strategy in which we have made several recommendations, some of them we have implemented, but, also, we have had a public campaign. Damon, who is the Director of Public Affairs, do you want to comment?

MR. THOMPSON: Sure. Hi, I'm Damon Thompson. I am Dr. Satcher's communications director. I'm pleased to announce that just a couple of months ago, we teamed up with the AABB, America's Blood Centers and the Red Cross. We provided the HHS studios at their disposal, as well as the personnel. They brought some people in who had benefited from blood products from around the nation, and we spent the morning cutting several public service announcements, and the AABB and the ABC and the Red Cross have all committed to working on the distribution of those PSAs.

If you like, I can get you some information. They sent us a storyboard with some of the photos involved. If you like, I can see that Steve transmits to you the storyboards for those, so you can see just what we have done.

DR. SATCHER: When do we expect those? I remember spending the whole morning doing the taping of those PSAs.

MR. THOMPSON: Right. You know, I'll have to check. I'm under the impression that they have already gone out. Sometimes it takes awhile to get into the pipeline.

DR. SATCHER: But we agree with you. It's something we need to really do. It's too late to add it to the indicators, but--

[Laughter.]

CHAIRMAN CAPLAN: Karen?

MS. LIPTON: I can just comment on the distribution. We do try to get them out. I think one of the things that we find is that we compete with so many other--when you are going into a public service announcement. And we have talked a lot about different ways to get around that. Some suggestion is that if you plan earlier and ask them to place them in December, you get a better result than asking them for next week.

But I do think there is also a contrary view that you get what you pay for. And if we are not willing to put money into purchasing advertising time that will get us at Super Bowl or something like that, that we will be always placed in the slots that the stations have allocated for public service announcements.

I also want to mention that there is an NHLBI, a committee to try to increase blood donation, and they have been looking at the Canadian campaign and trying to look at different ways, and I think they will come up with some very productive recommendations for all of us, in terms of trying to put together both the national campaign, which I would call an awareness campaign, and then coordinating that at a local level with recruitment, which really has to occur in the communities.

DR. SATCHER: I know I have gone over my time. Damon knows a lot about the franking issue, because I think he was working in Congress during the time when the situation was different, and the decision about not allowing franking privileges for the Surgeon General was not limited to the Surgeon General. Basically, except for Congress, they were done away with. But, will you say something about this, Damon?

MR. THOMPSON: Yes. It was part of the budget agreement, and it had to do with the Postal Service budget and getting more efficiency out of the Postal Service. The Postal Service agreed to be able to achieve a certain amount of savings, but, in return, they wanted to be relieved of the responsibility of providing free postage and expense for all of the agencies of government.

So, no agency was particularly singled out or anything. It was part of an overall budget agreement. I should also note that as far as the 90-day ban on mass-mailing for Congress, that does not mean that Congress has to sit on its hands on this message until after the election. There are many things that are available to them, many resources available. There are radio and TV shows, which they do, newspaper columns, town hall meetings. There are still many avenues available to them to be able to disseminate this message, and it will simply be any mass-mailings, and that is just to duplicate the verbatim letter and send it out to each doorstep. That will probably have to wait until after the election, but that doesn't stop them from communicating the message from now to the election in many other ways.

CHAIRMAN CAPLAN: Well, I want to thank Dr. Satcher for coming, and you should know that the committee is more than willing to try and push forward some of our recommendations in tandem with you when the letter goes. You should feel free to tie into our interest in making sure that the system is available to respond, as well as to notify.

DR. SATCHER: Thank you very much.

CHAIRMAN CAPLAN: Thank you.

We're going to hear next from Hal Margolis about basically where we are with the notification and hepatitis C information programs that we've been trying to push forward and track.

At the last meeting there were members of the committee who expressed interest in having an update on this important area, so--in terms of CDC activity, so Hal has agreed to present to us on the latest situation.

While I've got the floor here, by the way, I always was interested in doing an empirical study to see if there was a correlation between insomnia and organ and tissue donation, looking at PSA targeting. Blood could be added to that.

DR. MARGOLIS: Thank you.

What I'm going to do this morning, was asked to do, is to try and focus on--is this thing on? Can you hear me? Is to focus on some of the issues in terms of look-back, and I kind of phrase it in--realizing that most of the effort and most of the concerns have been around the issues of targeted look-back, but I think as we recognize, it's not the total answer to the issue and the problems.

And then I'll also touch on some of the things that Dr. Satcher mentioned in terms of CDC's efforts in terms of hepatitis C education and identification of infected individuals. I think one of the things we've all learned, is that while we have initially focused on identifying persons who are infected by transfusion, that as soon as you start talking about hepatitis C, you actually start talking about all this group, and you really can't wall these things off.

I have given everybody a copy of these overheads, so you shouldn't have to take too many notes in terms of the direct data. This kind of gives the summary. We've used the denominator of an estimated 300,000 individuals who have been infected among the 4 million estimated by blood transfusion. The data that Miriam Alter presented the last time, which until the next survey, but based on the power of that last survey, gives us an estimate that about 1,600 individuals have been identified through the targeted look-back, which, unfortunately, only represents about a half of one percent of all the infected individuals.

What you all want to know is this last part, is that, okay, and so how well has our general look-back effort done in terms of identifying everybody else? I think you got some glimpse of that in the targeted look-back data, which indicated that about one-third of these 1,600 individuals already knew their hepatitis C status. And so, again, I think we have to at least presume that, as defined, general look-back has been having some effect.

I put this up here just to remind everybody that there are a number of reasons why targeted look-back is not going to identify everyone. The single donor, even the donor with multiple donations who didn't come back after HCV testing came in place. And then a number of issues about the recipient, including, you know, the obvious, you can't find them, they changed their name. And the last one, which I think we never discussed here, but which is a very real issue, is that many people in the United States in fact have been transfused outside of the United States and they're among our American citizens, and in fact, as we look at this from a public health perspective, that's also an issue, and again, targeted look-back was not going to identify those people.

This one's the sound bite. You know what the recommendation is. And now what our challenge has been is how do you put this into the context of what we at CDC have been calling now our national strategy for prevention of hepatitis C, which has four components, very simple: prevent new infections; identify those individuals who are infected, and make sure that they are evaluated for liver disease and treatment; surveillance and research in terms of the issues that we don't know about.

Now, what we have done from a CDC perspective is, okay, how do you get this out there? How do you deal with both the public and private sector in terms of implementation of any strategy? And we've really focused in four areas, and you know, you've heard from me and others on my staff and other in the PHS that in fact communication of information about hepatitis C has been our number one priority, and I'll show you some data that says, "Boy, we're sure not there, but we've made a lot of strides."

The other big issue, which Dr. Satcher brought up and which we're just beginning to do some things on are what we call state-based prevention activity, and when I talk about state-based, it's not all just public sector, it is in fact public and private, and I'll give you some glimpses of where we are at this point.

Obviously, surveillance to figure out how well we're doing is key to this, and again, I think everybody on this committee knows the issues about hepatitis C and the difficulty of surveillance, but I'll show you again some glimpses of things that may help us.

And then, lastly, you know, we don't know everything, and so there is a research agenda to this, which I will not discuss at all today.

In terms of the communication issues, as I've said, we've primarily focused on education of health care professionals. The other big issue has been public service advertising or general public education, and then education of persons at risk, in the risk groups, and as I said, we have started at CDC. All of our effort over the last two years has really essentially been focused on the transfusion recipient. But as we have seen, as we put out just general information about hepatitis C, other risk group issues come up, and very quickly you're dealing with the whole universe of risk of HCV infection. We've only now begun to target some activities at injection drug users, and most recently, there was a joint agency symposium on hepatitis C or hepatitis and HIV in the injecting drug use community. It was held in Baltimore and co-sponsored by CDC, NIDA, CSAT, which is the Center for Substance Abuse and Treatment, and really realizing that the issue now in this last population is one that everybody said, "Oh, gee, it's HIV that's the problem." In fact, now drug users or people who had previously injected, are now dying from their chronic liver disease because their HIV disease can in fact be managed in terms of long-term treatment.

Put at the bottom here are the array of things that we are doing which have gone--and which we are funding at CDC, which include cooperative agreements with a number of NGOs, and in fact, there's a new round of funding that has just begun that is going to expand out. I can't tell you who everybody is because the awards aren't officially out yet.

Starting with the recommendations for hepatitis C control in 1998, which really gave the blueprint and the framework for how we're going to PSAs, to distance learning issues on the Web--and I'll give you some of that data later--to the STD and an HCV hotline that is in fact available to a group that you probably aren't aware of, called the STD Prevention Centers, which exist--there are 10 of them around the country, and in fact, train both practitioners on the medical direct physicians as well as others dealing with STDs and prevention of these diseases, with counseling messages. You know, again, one of the strenghts of HIV prevention is in fact formal counseling scripts. How do you do it? How do you do client center counseling? Well, that's not there for hepatitis, and in fact, we're developing those now, and those will be in the PT centers within the next six months or so, and again, this available to both, and heavily used by both the public and the private sector.

DR. EPSTEIN: Hal, I think that this very broad-ranging effort on targeted look-back related to blood transfusion is commendable. But what troubles me is that it's been estimated that only somewhere between 4 and 7 percent of all of the living people with HCV got it from transfusion. And the question is what percent of that larger majority, around--round figures--95 percent, do we think are reachable through general look-back strategies and where are we on those?

DR. MARGOLIS: Well, as I'm saying, we don't have any idea. The fact is we don't, and we don't have any reasonable mechanism to look at that. We're currently, as I say, I think some of these state-based surveillance systems, once states can look at who these people are and figure out how individuals acquired their infection, will be able to help answer part of that question; in other words, in New Mexico, what proportion of those 17,000, in fact, had transfusion as their risk factor? And from that I think we can then begin to estimate.

Basically, we have to get some population-based approaches to looking at general look-back. And we are sitting right now trying to figure out how best to do that in a way we can afford it, and that's really our next step. We put our major effort into looking at the effectiveness of targeted look-back, and now we feel we need to do, as we have done with the targeted look-back, is look at the general look-back kind of in interval or, you know, looks.

So we need a baseline right now to see where we are because everybody says hardly anybody knows they're positive, yet you and I know there's a lot of HCV testing that goes on each year, and I know there are a lot of positive people in state health department records. So we just need to figure out who they are and what their risk factors are. So as I said initially, we don't know, and I think that's the difficult part.

DR. KUHN: Dr. Margolis, there was a question I had, and I was thinking about as you were talking about methods and modes of communicating this to the public, and the question that came to my mind, and I think it kind of follows along with what Jay was speaking, is if I'm an average American working person, I'm busy in my job and perhaps I, I mean, I received either a blood transfusion before 1992 or I had it through another mode, and I have Hepatitis C, but I don't know it because I hadn't had any need to go to a doctor because the disease is not presenting in any way, shape or form, what is the best method or mode of communicating or informing me that I may be at risk?

And I'm concerned because there are people out there, and they have busy lives, and how are we communicating to them that they are at risk?

DR. MARGOLIS: Well, again, I think we've taken a lot of different approaches, from the surgeon general's letter to those PSAs to what we have heard, and we've done over a dozen focus groups in different parts of the country with lots of different people of different races and ethnicity. And they all say to us, "I'm not going to go, most likely, if I'm--" and these were people who have had transfusions, but they all essentially are saying, "I'm probably not going to go to my physician just because I had a transfusion. I expect my physician to ask that question when I go there." And that we have heard over, and over and over again. I mean, that was the very first data. And that's why we think that, and people do go to physicians for other reasons and as part of a standard health history.

Now, for instance, the American College of OB-GYN has now put this in their health practices, their latest health history. So they've been moving forward with this. So what I'm saying is, and it's what this group told us, is that the message has to be on both sides. We have to get it to the public and get it to the public as close to their health care setting as possible is what, again, the educated approach was. And the other is that physicians have to ask the question because if they don't ask it, it's not going to happen. I mean, that we've heard both from the patient side and from the physician side. So that's where we're trying to go. I mean, I don't--it's difficult.

DR. KUHN: Yeah, and I understand it's a dilemma right there. But, again, I kind of look back to where most public citizens are all of the time is they are on the road, they're driving. And I think one of the most effective, that I saw, ways of a PSA were the yellow eyes, that poster. That was a very effective way of getting people's attention and maybe that needs to be looked at again, done on a broader scale across the United States. I don't know how, but there are people in marketing who have a way of being able to reach the mass public on how to inform them that they are at risk if they meet one of these entities.

DR. MARGOLIS: And just to assure you that we/CDC aren't doing this alone. We're doing this with the big marketing people. So that's why there's a lot of different approaches out there. But, no, I agree, and again the yellow eyes, which was done by the American Liver Foundation I think is still running.

The big issue, though, is does it get somebody into the physician to get the test? And that's where the link has to occur. But you need both, and we agree.

CHAIRMAN CAPLAN: Keith?

DR. HOOTS: I'd like to congratulate you, at least, from a couple of anecdotes that I've observed. At least two patients over the last 2 months who clearly had been told long ago they were HIV infected because they were in an at-risk group and had been presumably educated, at least we think we've educated them, but as you indicated, sometimes it takes reinforcement over and over again. These were two individuals who hadn't been seen in the health care system for several years because they had done pretty well, but came in not only asking about their Hep C and commenting about, well, you know, it's been in the news a lot, and I wanted to know, and they came with specific questions, which indicated to me that some of this message is getting out even to people whom you would think would be the ones who wouldn't need it the most. But the fact that they translated what they--just some peripheral knowledge that had probably been long since forgotten into specific questions suggests to me that, at least in that broad way, and clearly what they said to me was that it was in the news and that they had been looking, and it raised questions in their mind.

CHAIRMAN CAPLAN: I have a question, actually, three quick ones.

I had occasion to be talking recently to a group of infertility clinics, and when they manipulate sperm, and eggs and embryos, it turned out that not all of them, but many, were routinely testing for Hepatitis C, among other things. So in addition to the scripts, one question I have is how is CDC working with the professional organizations and societies to make them have, as part of their standards, testing for risk behavior in the good standards and practices area?

DR. MARGOLIS: We go to a lot of meetings. In fact, I was just at the Infectious Disease Society of OB-GYN and working also with, again, OB-GYN's Practices Committee. Miriam, and I and others in my group spend a lot of time working because the reality is the tough part of this is getting this uniformly into medical practice.

And that comes from several ways, getting professional organizations to say we agree or we're going to rewrite the CDC recommendations for our own organizations, and, again, that was part of in that February meeting, and some groups are doing that. And then the subspecialty groups within an organization has to do it. And let me tell you, you have to knock them down one at a time. I mean, there is no other way.

We actually now have a list, and we went back after that February meeting to find out of the 150 groups that were invited and for whom we even gave dummy--dummy--but, you know, dummied up articles for their newsletter. How many of them have done something with it? Well, 25 have. So they've actually put it out in their monthly newsletter or magazine, and then a much smaller group are actually putting it into a committee to write recommendations. And that's what we're tracking and working with them.

And there is really no other way to do it because that's our current medical system. But what it really all starts with were the CDC recommendations and recommendations from this committee and others that begin to say now we need to move this forward.

CHAIRMAN CAPLAN: The second question I had for you is at some--we spent a lot of time, and we'll probably spend a lot of time today starting to or revisiting issues of cost benefit, trying to achieve improvements in safety. And in one sense, as Jay points out, Hepatitis C is not primarily a blood transfusion issue. On the other hand, I think the committee has always understood that there are special obligations to notify, and look back and maybe spend more because of the nature of the blood system. In order to cement trust in the system, you may want to do that. And also, to be blunt, it may be easier to carry some of the public health factors about Hepatitis C on the back of the blood issue. So there it is, and that's what it's going to do.

At some point, however, in the expenditures, cost-benefit expenditures, there comes a time, I suspect, at which we start to say you ought to get a test if you're older than 20 or older than 30--I mean, forgetting about the individual risk factor thing. Do you envision a time, has CDC been thinking about simply saying, look, anyone over the age of "X," risk factors or not, we really should make that part of routine testing, as part of what gets done? Cost and so on I understand with the--

DR. MARGOLIS: We've not done cost analyses. We've done it on kind of an identification effectiveness analysis. And that, again, is the reason, for instance, that while HCV is sexually transmitted, the number of people who have the types of sexual practices that would put them at risk of HCV is so incredibly large that the effectiveness of identifying people, such as doing routine testing in an STD clinic.

Now, we're looking at this in a number of the demo projects, and there are data coming in. And, again, the effectiveness of routinely testing, even in an age group, turns out to have an incredibly low yield. And so we've not done it as a formal cost analysis where, actually, it will happen, but we've done it as an identification effectiveness type analysis, and that's why we haven't used those approaches because they just don't come close to any of the things that we do in terms of other public health activities.

CHAIRMAN CAPLAN: Last quick question. I see that this letter probably, sounds like, is going out under some disguise or stealth mechanism. So if the letter is going, and there are PSA announcements in somebody's basement waiting to be shown at 2:00 in the morning to various people, and you have activities underway, can the committee know or can we be assured that we could get an integrated push?

This is a wonderful opportunity, it seems to me, to really get the attention of our political candidates, congressional candidates, all kinds of people, if we could get a coordinated push around the appearance of the letter. So is CDC thinking now about what to do when this letter goes?

DR. MARGOLIS: Our problem has been we get the sense this letter is not all going at one time. And, again, I'm just talking about some of our--what little bit of forecasting we can get. The other part is some of these things which I've told you, such as the next piece to the physicians, is in the pipeline. When that's going to happen may not quite come together with the letter, to be honest, in terms of just the lag time of the funding, and what the contractor produces and what we all think we want. So we are ready to be receptive; in other words, the hotline has been geared up. There are more people.

We have tried to do some forecasting as to what may happen, and if this upward trend puts another set point in there, we can do that. In terms of other pushes, you know, we can reissue some of what we have. Whether we'll have a new rollout like we did at that May thing almost a year-and-a-half ago, I honestly don't know. But it's a good idea, and we'll sit down and strategize.

CHAIRMAN CAPLAN: Steve?

DR. NIGHTINGALE: If I can make one additional comment in response to Dr. Caplan.

There is not necessarily a conflict, but there should be a balance between an integrated approach and a sustained approach. One of the things that I have taken from Dr. L'Enfant and his very successful management of the National Cholesterol Education Program is his very firm belief, which I think is backed up by very extensive data, that the duration of a public education campaign is of comparable importance, if not more than comparable importance, to its intensity. The primary purpose of the Department's efforts is not to achieve a campaign that gains intensity at a single point in time. In fact, there is probably less enthusiasm for an intensity-driven campaign within the Department than there is without. I think there is more enthusiasm within the Department, and I believe I am speaking for the agencies as well, of the duration of the campaign.

What we're both looking for is effectiveness of the campaign, whether or not intensity or duration is the most important, perhaps will be debated. There is room for both. But from within the Department, duration is what we're looking for.

DR. PENNER: Two quick comments and a question. The learning curve for the health professionals is directly related to Board examination questions, and it would be a strong suggestion, if it gets on the Board, it'll be picked up very quickly.

Secondly, the PSA letters, as they come out, require I think some attention on emphasis. When we get letters that start out with substance abuse up top, for example, the stigma of that suddenly turns off the rest of the message. You say, well, if these are drug users, that's fine, and forget about it. So if you emphasize that, and I think this will bring back the question that was already brought up, is it can be carried as a message and part of the transfusion and blood which I think most of the physicians, health care workers and the public respect. So they'll look at it a little bit more carefully than if it just comes, oh, another drug abuse situation and then just discard it.

The question I have is that 3 years ago we dealt with a look-back situation and made some recommendations. And at this point, what percentage of the blood banks do you believe have completed the look-back?

DR. MARGOLIS: The data that Dr. Alter presented was that in April it was about 85--again, the estimates were based on 85 percent. It was around 85 percent. And the next survey, which will be done early in 2001, I mean, we projected essentially it's, you know, it's done. That was on 85 percent of the data reported back. Now, many of them had already done all of their work, but didn't have the data in terms of being able to report the numbers.

DR. PENNER: To 1990 or to 1992?

DR. MARGOLIS: Oh, excuse me. That was, actually, that was back through '90, again, that was the--

DR. PENNER: The first-generation testing.

DR. MARGOLIS: No, that was not first--this was only second-generation testing or second-version testing.

DR. PENNER: So what's happened on the first-generation testing that we have asked for the look-back to be reviewed with the specifications that we had made with regard to cutoff period? What's happened on that end?

DR. MARGOLIS: That we have done because at the time when the survey was done, again, essentially last January or February/March at that time, that wasn't in that survey. That would then be put in the next survey. And so we realize we're now going to have to look at version one effectiveness data, which will probably carry us into 2002, in terms of getting that data. Do you see what I'm saying?

DR. PENNER: Yes.

DR. MARGOLIS: In other words, all of the data I've shown you so far is for version two, for the second generation. And so for us, for the evaluation, it has to be added to the questionnaire that will go out in 2001.

DR. PENNER: So you're really not sure what that part of the look-back is--

DR. MARGOLIS: Don't have any data on that.

DR. PENNER: Mike, do you have any idea what that might be, just offhand?

DR. BUSCH: Well, just I remember when we looked at this there was data from Stanford that indicated that their actual incremental pick-up with the version one-driven look-back was quite low just because of the tracing issues, the lack of records, the number of patients alive.

In terms of the first-gen look back, I think most programs have implemented it. There's actually not a formal final FDA recommendation, in terms of exactly how to conduct it. But sort of verbally, I think BPAC meetings, et cetera, FDA has indicated their position. So most programs have initiated it and I think probably completed it.

DR. PENNER: With the first part, but the other part--

DR. BUSCH: No, I'm talking about the first-generation-driven, BIA-driven look-back programs have, to my knowledge, been implemented and are probably well on the way to completion.

MS. LIPTON: If I can just, the difficulty we don't know. I mean, we're pretty confident about what the blood centers have done. When you get into more problems is trying to ascertain whether the hospitals have actually been able to make the contact. I think most blood banks got on it right away because if you were going to go through the records once, you just wanted to accomplish it. But as to how, you know, finding patients who were back much further I think was a very different issue. And there are time lines. I think everyone is working diligently. But, Kay, you don't know, do you? I just don't think we know right now. And we periodically send out surveys, but we don't have one on the--and it's really the hospitals we need to hear from.

DR. GUERRA: Harold, a couple of public health questions and concerns.

Most states now are doing universal screening for HIV and Hepatitis B in their populations of women that are being taken care of in labor and delivery room suites or during their prenatal care, and it must be documented. It is a requirement, at least prior to dismissal of the infant from the hospital because of certain therapeutic decisions perhaps that have to be made.

Are we anywhere close to considering that as a universal recommendation for prenatal populations, given what obviously is a tremendous increase or at least the suspected increase in serum prevalence rates is one question. And the other is within some of the efforts that are taking place, are we also doing something to try to dispel the myths and misperceptions about Hepatitis C? We often get questions about household members being in contact with somebody that is identified as being Hepatitis C. And it's almost a real stigmatization that occurs in infants or children in day care settings, where a parent has declared themselves to be Hepatitis C, and it becomes a matter of public concern.

CHAIRMAN CAPLAN: I just wanted to piggyback something that I forgot to ask onto that question. We had a big battle, which you're aware of, Hal, in Philadelphia about firemen getting infected with Hepatitis C. And I got a lot of calls about this casual contact transmission, bleeding contact, that sort of thing.

DR. MARGOLIS: I would venture to say we spend 50 percent of our time, professional time, both public inquiries and actual time "doing the studies," to dispel some of the myths, actually maybe working from the fire fighters back. Again, unfortunately, there are a lot of things that go wrong out there, so incorrectly reported data, which turns into somebody's political agenda, which doesn't serve anybody. And as you saw, we moved pretty quickly to test old data sets, analyze data, get an MMWR out and try and answer and at least hopefully set the information platform straight.

The same goes on with the question of transmission. I think there are, again, good data, and those get handled both through hotline and a lot of calls, and, no, we don't have a pamphlet that says what do you do in a day care center. That's on the list that needs to be written. And so that's where, and again, we try and clearly work with our partners to identify certain groups or information areas in some of these cooperative agreements that we do. I mean, that's frankly how we work is to let them put that information together and get it out. And so some of that type of, you know, those areas where we're getting a lot of inquiries, we then try and generate, you know, some written information or put something on the website and go that way with it.

So it's kind of both, if we need the data--you know, tatoos is, again, still one of the big issues. So there are RFAs out there, there are awards that have been made for looking at tattooing in various settings to, again, look at risks. So sometimes we need to generate the data, which is the research side. Other times it's just communicating it that we try and deal with.

The question about perinatal transmission and screening pregnant women, there is a CDC study that's being presented now and is in the process of being written up for publication that showed, again, that the rate of perinatal transmission is low. It's about 3-3.5 percent. Transmission only occurred in an HCV RNA-positive woman. But, in fact, since this was actually a prospective multicenter study, it showed two additional things:

One, it showed that there was an increased risk for internal fetal monitoring--somewhat, you know, that's kind of a logical thing, but it's never been looked at before; and the other that there was increased risk with prolonged rupture of membranes greater than 6 hours. And actually those in the multi-variant analysis part of it actually became the only dominant risk factors, in fact, over HCV RNA titer in the mother.

It raises the question of, given that kind of information, is there something we ought to be doing differently in terms of identifying HCV-positive pregnant women because in the past there wasn't anything you could actually do as an intervention. And, again, going back to how you make things happen in practice, we're currently working with ACOG, and their Fetal Medicine Committee, and their Infectious Disease Committee to review those data and see if it warrants such a recommendation for screening because that gets back into that issue of, you know, identification of all of the issues and what one might do.

So those are new data that, as I say, have been presented, and several meetings now are being put together for publication and are being worked on by the groups that would be most affected by it. So we are trying to move in that direction.

DR. GUERRA: But beyond, obviously, the port of transmissions or just they're serving the purpose of identifying the Hepatitis C women in child-bearing years, that obviously could then be put into a registry for tracking and for doing the other kinds of preventive measures.

DR. MARGOLIS: Again, it goes back to a bit of the question that Dr. Caplan asked, which turns out that actually in that age group, if you just did it uniformly, you're identification rate is actually very low because that's actually one of the lower-prevalence areas. We do have recommendations that if women have risk factors, they should be screened. And, again, if you go around and talk, especially to large inner-city OB-GYN and delivery services, many of them are screening, some of them now to the point of routine. They're definitely asking questions.

And, again, ACOG has put that in one of their, you know, in their newest screening questionnaire. So, again, it's this issue of, you know, should you do everybody or should you do some, and some of the new data on possible intervention for the infant may change the equation in terms of should we do all. And that's where are right now. And as I say, this is just in the last couple of months. So we're trying to deal with it with various advisory committees.

DR. GILCHER: A couple of comments from a large regional blood center that might be helpful.

With respect to first-time donors, it's 95 percent of our HCV hits are in first-time donors. It's actually 95.4 percent at our blood center. We've gone back and queried these individuals. There are not a lot, but we've queried them. And what we have found is that, number one, they were not seeking tests. They really did not know they were infected. What we did find, though, was that about 50 percent of them did admit, even though they had denied this at the time of the donor screening, they did admit that they had tried IV drugs even one time.

We then added another question, and this is really a comment that I'd like you to comment on. We said, "Do you have any friends that are Hepatitis C positive?" And almost every instance, they have friends. And, in fact, when we query, it's those friends with whom they tried IV drugs even one time.

The other interesting finding that we have now from our NAP data, and I can only speak for my own center, is that roughly--and this is a donor population, not a general population, is that about 25 percent of the donors who are RIBA-positive appear to have cleared the infection. That's higher than what has been found in the general population. But of that group, interestingly, about 30 percent of the women have cleared, but only about 17 or 18 percent of the men appeared to have cleared the infection. I'd appreciate your comments.

DR. MARGOLIS: Starting with the last one, when we looked at the NHANES data, 25 percent were, in fact, RNA negative, realizing that's a one-time RNA test. But only 75 percent were positive. The younger you were, the more likely you were to be RNA negative. And, again, that gave us some pretty wide confidence intervals, but there are other data that kind of keep coming out that way. And, again, in that data set, as you recall that African Americans had the highest chronic infection rate, at about almost 90 percent. And, again, those data and other studies have been seen that way. So that when you put that together, I think that's probably what we're seeing, what you're seeing, and it's part of, I guess, better knowing the biology and the natural history of the infection.

The issue that an HCV-positive individual may have another positive individual either in their family or close to them, we're now seeing again, in a number of data sets that we're analyzing, and where again I can just give you from the NHANES that we're looking at, for instance, in families actually close to 30 percent of the families had more than one HCV-positive person in it. But when you actually look genetically, these aren't the same viruses. So it wasn't that they were transmitting to each other because, unfortunately, NHANES didn't have all of the risk factor data we would have liked in NHANES 3, but from what we have, it seems they had similar risk factors. And, again, I think that is beginning to be noticed, and we just need to get a little more precise with how common that is and how we can use it to identify individuals. It's not that this is, you know, intrafamilial transmission, but it's shared risk factors. And I think, frankly, we need to figure out better how to use that information so we can identify people.

But, yes, we've seen that in the NHANES, we've seen it now in a couple of other data sets, and we're trying to, again, figure out ways I guess really to best understand it so we can use it for identifying people.

DR. DAVEY: Dr. Margolis, I think we can all agree, and the comments have reflected this, that the toughest group to approach is the IV drug-abusing community. Probably over 50 percent, I believe, of infections are thought to be by that route, as Ron and others have pointed out.

Could you comment on the CDC's efforts to link their control measures on Hepatitis C with other government agencies that have responsibility for managing drug abuse. And secondly, specifically, what's the CDC policy on clean needles and providing clean needles for a prospective management of this infection in that community?

DR. MARGOLIS: I think probably the best indicator of what the Public Health Service--how we view this was this meeting in May in Baltimore called Drug Use, Hepatitis, and HIV--or I can't remember which way they had it--bringing it all together, in fact, sponsored by the agencies who have responsibility both for prevention, treatment, and control of substance abuse.

When you then really start talking to drug treatment center directors as well as the research investigators and trying to--how do we figure this out, I think everybody's well aware and I think now is beginning to believe that the paradigm for prevention of infections among injection drug users, while HIV has been the focus, it's really HCV because it's there immediately, and, in fact, I think it's made us all--and, again, based on data that was done in syringe and needle exchange programs, actually sponsored by CDC, show that it's probably things other--I mean, the syringe and needle are extremely important, but transmission also goes from the rest of the activity, and to put it kind of quite bluntly and frankly, you need universal precautions in a drug use setting, then reflect on that and realize how difficult that is. But that's, in fact, what the issue becomes. It's everything else that's transmitting, and, in fact, we've done studies to ferret out those other things, including blood on the hands and all those things that go on with drug use.

So you still got to get at the prevention side. You have to figure out how to interdict in terms of those who are using. And let me tell you, one of the things that I've seen--and I'm kind of new to this--is that in the states where we have now seen hepatitis C coalitions from a state perspective put together, it has heavily driven the issue of drug treatment. So that, again, several states now have moved drug treatment actually into clinical public health settings instead of that "over there" kind of situation. And these people are now talking to each other. And, you know, there's been real changes in total philosophy. Yes, CDC recommends that syringe and needle exchange should be carried out. The Federal Government doesn't fund it. So that's, you know, where there's some divergence.

But, in fact, it's very effective, and most recently some involvement we've had with vaccinating drug users in exchange programs shows that it's highly effective, can be done, and you can access people.

So I think things are changing, and the people who are supposed to be dealing with this are talking to each other a lot. Is there money? That's what Fernando asked earlier. Unfortunately, no, there's not a lot of money that's coming together with this. But I think at least we're finally talking about it and realizing what the issues are.

So, you know, that's kind of--this is new and this is evolving, and evolving pretty rapidly.

CHAIRMAN CAPLAN: Maybe what we will do is take one more question from the Committee. I might look to see if there's one question out in the audience. Then I will finally relieve Hal from standing up here so long.

Paul?

DR. HAAS: It's impressive the amount of work that you have done, and I have to believe it's also very frustrating in terms of how slow the information comes out. And this part might be the wild part, but I'm listening to this and thinking of watching these ads now showing up on TV for different types of pharmaceutical drugs and the awareness it has, I suppose, given the patient showing up at the doctor's, probably asking for the drugs for the wrong purpose, but at least they're aware that it's out there.

I'm just wondering, now that we do have treatment for hepatitis C, whether some of those drug companies might be willing to start funneling dollars in to help the continued promotion that you're doing.

DR. MARGOLIS: In fact, the PSAs, you know, the TV PSAs, which are very expensive, were funded through the CDC Foundation and a drug company consortium. We just didn't have the resources directly from what we had. And so we haven't gone to the subliminal advertising yet, but we're clearly partnering. And I think it's been working well. And it's also including immunizations. So when I talk about, you know--because again, as Dr. Guerra said, this is the whole thing.

I mean, I don't know if you've heard me say it here, but our buzz word around CDC now--and this is with the AIDS groups and others--is one-stop shopping. I mean, the reality is you've got to think of these all together, and all the bloodborne infections are together, and we've got to start talking about it that way. And so we've been trying to do that with industry.

CHAIRMAN CAPLAN: Could I just ask you to identify yourself for the record?

MS. JACOBS: Yes, Mary Beth Jacobs from FDA. I have a follow-up question to the last one.

About a year ago, I saw an ad in the Washington Post directed toward women from a company saying: The next time you go to your gynecologist, why not ask if you should be tested for hepatitis C?

Has CDC evaluated the effectiveness of that type of direct ad to consumer, not the approaching of having companies fund the PSAs, but the comparison between that kind of approach in someone who has not yet been diagnosed?

DR. MARGOLIS: No, we haven't.

MR. CAVANAUGH: Dave Cavanaugh, Committee of 10,000. The occasion for this presentation is the letter, which is stopped. There are several barricades to the letter going out. We understood kind of elliptically from Dr. Satcher that a sentence is being changed, and I don't know if that means the letter's been pulled back or never went to other Congressmen. And even with the ban, is there any kind of assurance that something will happen that any number of the 435 members will be sending it when they come back in January?

Thank you.

DR. NIGHTINGALE: Just for the record, I spoke to Mr. Slobodan of the House Commerce Committee yesterday. We do have a plan, and we'll be in touch with you. There are separation--because of the separation of powers, I'm not going to say anything else right now, but I will say for the record that we continue to work actively with the Congress and fully respectful of their prerogatives.

CHAIRMAN CAPLAN: We will come back, undoubtedly, to the letter with, I'm sure, other illuminating responses. But let's stick with Hal for now. I'm going to take one more question, if that's to Hal, and then we'll take--we're getting ready for a break, although Steve has one comment to make before we do.

DR. SAYERS: Merlyn Sayers from Carta (ph) Blood Care, which is the community blood program for Dallas-Fort Worth. Heaven forbid I should delay getting into the break, but some comments that relate to remarks by Dr. Satcher, Dr. Busch, Dr. Gilcher, and Dr. Margolis.

It's not all that long ago that community blood banking was a lot simpler. All we really needed to do was recruit donors, collect blood, test the blood, make components, and distribute it. But whether we like it or not, the role for community blood programs to become centers of community and public health is increasing dramatically, and that's understandable. Something like 40,000 volunteer donors a day are scrutinized by an extensive health history and extensive serological testing. So our role in community and public health then immediately relates to counseling those individuals that have been identified as potentially worthy of counseling.

That community and public health role then gets extended with targeted lookback, and I have no doubt that that role is going to be extended even further when this letter comes out announcing to the nation at large what the risks are of hepatitis C, the silent epidemic. And whether we like this or not, I have no doubt that even though individuals will be cautioned against going to their blood program to donate to get tested, I would not be at all surprised if we do not see a small surge in individuals who are found to be reactive in HCV because simply they're one of the many millions that do not have health care coverage.

So at every point, the cost of doing business at blood programs is increasing, and a significant element of that increased cost has to do with the fact that we now have a community and public health role.

Now, we cannot exactly pass those costs, understandably, on to the individuals that we sell blood to. Goodness knows they can't get reimbursed for the additional testing that we're doing. So, Dr. Margolis, you posed the question just a couple of minutes ago, is there the money? And what I'm wondering is, if there is the money which is going to recognize that community blood programs are now a very valuable and very important source of community and public health, could there be creative ways to fund these public health programs which are centered at the blood centers?

End of sermon.

DR. MARGOLIS: Well, let me just tell the group, the Committee, because it's public record, you know, our budget through this year, the end of this fiscal year, is about $13 million. So that pays for all these things you're hearing about and some things you're not hearing about, like the sentinel counties, the NHANES, all of those things, and also pays for some staff. Congress, in the current President's budget for 2001, the estimate mark is an additional $5 million, and that's kind of where we are, and that's how we put it together.

There's been testimony in a number of hearings as to what the estimates might be for a program that would fund counseling and testing and support of the various community activities that you're describing, and that's in the range of $40 to $60 million per year. So we're a long way and, you know, we're trying to be as creative as we can.

Yes, we think it ought to be a part of the mix, and if you look at HIV, you know, some of those types of things do occur. But we don't have that for hepatitis C.

DR. GILCHER: Merlyn, in response to your statement, something that we have done for over 12 to 15 years is offered what is called non-donor testing. We clearly found out that there is a segment of the population who wants anonymous testing not at a doctor's office but are willing to pay for it. And we believe that that has actually enhanced the safety of our blood supply and has removed test seekers from donating blood because we now offer this kind of program through our system, which is really in a sense a public health maneuver.

CHAIRMAN CAPLAN: Okay. Thank you, Hal.

Steve, you wanted to say a word about the WHO issue that the Secretary brought up, I think.

DR. NIGHTINGALE: A word or two, and about several subjects. I am taking over Dr. Snyder's obligation to be brief before the break. I'm not sure that I will succeed.

Hal said that you had to hear a message seven times before you really understand it. This will be the tenth time that the Committee will have heard either in full or slightly abbreviated fashion the conflict of interest statement.

Relative to what we're up to, I would ask you to listen to it at least as carefully as you have on the previous occasions because there are some very important things in it, and it reads as follows:

The following statement 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 Committee members present no conflict--potential conflict of interest when evaluated against this agenda.

In particular, specified in Title 18 of the United States Code at 208(b)(2), a special government employee, which all Advisory Committee members are, may participate in a matter of general applicability, for example, advising the government about its policies on 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 the decision of the Committee--and here is the key point--provided that the matter will not have a specific or distinct effect on the employer or the employee other than as a member of that class.

The example give in 5 C.F.R. 2640.203 is as follows: A chemist employed by a major pharmaceutical company has been appointed to serve on an Advisory Committee established to develop 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 a class of all pharmaceutical companies and other research entities that are attempting to develop an AIDS vaccine.

In the event the discussions involve a specific product or a specific firm in which a member has a financial interest, that member should exclude him- or herself from the discussion, and that exclusion should be noted for the public record.

With regard to the other meeting participants, we ask in the interest of fairness that they disclose any current or previous financial arrangements with any specific product or any specific firm on which they plan to comment.

The point here, the tenth time, is that conflict of interest is an extremely important issue in a democracy. The process of regulation--it's very important that we do this right on several different levels. We have and will continue to talk about issues where the advice--we cannot get the advice we need as a government unless we get it from people who will have a conflict of interest. This Committee is intentionally much more inclusive than some of the other Advisory Committees, and I think that has been one of its strengths. And one of the things that--perhaps my personal agenda is to try to make other committees stronger by being more inclusive.

I believe that we have in the statement that I just read, and, as you can see, I deeply respect, a principle analogous to the principles that we will be trying to elucidate--to gather from you today on the broader issue of blood safety that goes part of the way but not all of the way. And that's why I wanted you to focus on it. The principle for conflict of interest works extremely well, I think, for individuals. Does it work as well for aggregate committees? That's where we fall short.

I saw the lawyer to my left give a knowing smile. I think there are a few others.

For example, it is perhaps not quite in our technical capacity yet to clone the chemist that I mentioned earlier and several times previously, but clearly a committee that was made up of 10, 18, or 24 clones of the chemist would not be an ideal committee. We really don't have the principles quite yet for aggregates as we do for individuals in regard to conflict of interest. How we develop a committee that is not collectively biased is something we haven't figured out yet. We have some standards, though, and I think you should look--when we make our disclaimers or our proactive statements that we encourage members of minorities, women to apply, that geographic diversity is indeed a criteria for membership on the committee, these are perhaps sentinels that we would use to see whether--as a first pass, but they're clearly not sufficient.

So as you are thinking today about either the certain matters or the principles, however we formulate the statement, I would encourage you to consider that we've come part of the way towards that but not all of the way.

Now, in that context, one other thing that I think we have that we don't use perfectly but I think use well is the charter that we have for this committee identifies people--the class from which we wish to draw nominees, and, in fact, this is my segue to the comments on our request for nominations for membership in the committee.

Our charter does not identify specific people who have chairs on the Committee other than that there are six non-voting governmental representatives. There is somewhat of a split between people on the left, people on the right, and people in the center. That is not cast in stone. That's something we're still working on, and comments on that either now or sometime in the future from the Committee would be helpful. But as we actively solicit nominations for membership in the Advisory Committee, we would be interested in nominations that make the whole Committee stronger rather than individuals.

One final point, of course, is that the Committee, while it might be the people around the table, we have made and will continue to make a deliberate attempt to act as much as we can as a Committee of the Whole. Dr. Caplan has been superb--and I would like to make that compliment for the record right now--in including members of the audience. The audience has been equally superb in their contribution, and for the record, thank you for your continued support.

With that, then, on May 31st, notice was published in the Federal Register, Volume 65, No. 105, page 34705, soliciting nominations of individuals to serve on the Advisory Committee in accordance with its charter. As Dr. Satcher noted, the terms of five members will expire on September 30, 2000. Appointments will be made for a term of four years, and it is now necessary to renominate individuals previously nominated.

In accordance with the Committee's charter, persons nominated for membership should be from among authorities knowledgeable in blood banking, transfusion medicine, bioethics and/or related disciplines. Members shall be selected from state and local organizations, blood and blood products industry including manufacturers and distributors, advocacy groups, consumer advocates, provider organizations, academic researchers, ethicists, private physicians, scientists, consumer advocates, legal organizations, and from among communities of persons who are frequent recipients of blood and blood products.

Membership is by secretarial appointment, and I can assure you that it is by secretarial and not by staff appointment.

A copy of the announcement is available at the back of the room. We have attempted to make the nomination process as simple as possible. We need to know who the nominee is, how to reach her or him, which of the very broad categories I just mentioned the nominee fits into, and that is only because of the requirement of the Committee charter, and a written statement of the nominee that, if appointed, he or she will serve.

We need a copy of the nominee's C.V. Additional supporting materials are welcome but not necessary. Individuals may and are encouraged to nominate themselves. In accordance with well-known Department policies regarding nondiscrimination and diversity, women and members of minority groups are encouraged to apply. If someone other than the nominee is the nominator, we need that person's name and address. If the nominator is a corporation, we need a human contact in that organization.

Finally, we need to receive the materials by 4:00 p.m. on August 31, 2000, which will be the 92nd day since the notice was published on May 31, 2000.

If anyone has any questions, please contact CAPT McMurtry. His direct telephone line is 202-260-1351, and it will not be changed until after the close of business on August the 31st.

[Laughter.]

DR. NIGHTINGALE: Now, to the statement of issue for the meeting, at your request you are meeting to discuss the role of various considerations in decision making related to new and additional safety measures. Dr. Satcher suggested the alternative but not contradictory title of what are the principles on which a blood policy to assure a safe, available, and affordable supply should be based. This is meant to encourage rather than to limit comment. I think one of the uses, perhaps the immediate use of the comments will be as the Department considers how best to support the efforts of Dr. Emmanuel, who you met at the last meeting, and certainly Dr. Epstein, who has made huge contributions to this process, to the meeting in Geneva on November 13-17 by WHO, the first Global Collaboration for Blood Safety. A copy of the announcement was distributed with your briefing memoranda.

We approach this with an open mind, with, as you heard from Dr. Satcher, a desire to participate in a constructive manner both in regard to the needs and the policies and the political conflicts of developed countries as well as developing countries.

Finally, having made that comment about the immediate purpose, that is, of course, not the only purpose of the meeting. The Department is aware, in part because of its response to your previous recommendations, of the issue of reimbursement for blood products and reimbursement for the services that are incorporated into the provision of blood products, many of which economists would call externalities. The issue of what the market recognizes and what it doesn't is one of which we are aware, but do not mind being reminded once again at this meeting.

The agenda for today's meeting is much less structured than it has been in the past and much less structured than I anticipate it will be in the future. The reason we have done this is to provide the members of the Advisory Committee and the members of the public in attendance an opportunity to say whatever they want to say on this issue and to do so in an unbiased context as possible. The one request I have, although I may not have honored it myself, is to keep it short.

CHAIRMAN CAPLAN: Steve, just for the record, some members of the Committee have asked me, having perhaps not been as intimately acquainted with the charter of this Committee as you are, with a new election how does that affect if there's a turnover at HHS, with the Secretary, how does that affect our business, our charter, what goes on?

DR. NIGHTINGALE: On November 9th, all bets are off. At the same time--I've actually--I've never gone through a government transition, particularly not being kind of in the--I don't want to call it "the bunker," but in the Secretary's office.

What I do anticipate, however, is that there would not be a complete change of administration. I am aware of very broad bipartisan support for this Committee. It's been incorporated into report language in the past. It's been expressed to me privately, and I communicated it to you because, folks, it's your work that has been recognized.

Where are we going? The speech that Dr. Satcher said was this Committee, I believe very successfully, has addressed six very complex issues. The burden of Dr. Satcher's--at least the text of his message was that these problems, while addressed, remain, have not gone away, and if we let them drop, they could become problems again very soon.

To give a little bit of my political feel for this, it is that the establishment of this Committee and the maturation of this Committee was a very labor and emotionally intensive process. I know of no one in the government or I think in the private sector who wants to start all over from scratch.

DR. DAVEY: Steve, one quick question about membership. Assuming the Committee continues, I would recommend--and I think we've discussed this--that we include a representative from the Health Care Financing Administration as a representative on the Committee joining our other government representative colleagues.

DR. NIGHTINGALE: Noted. Also, I think membership on the Committee by a nongovernmental individual who may have expertise in that area would also merit consideration and will be considered.

Dr. Davey did remind me to say one of the many things that I wanted to say and didn't say when I was reading my text real fast: Membership on this Committee is a membership of individuals in accordance with the charter. We nominate, the Secretary approves individuals for membership in the Committee.

Having said that, I would say something else. The Committee needs new blood. You get tired of listening to me read that conflict of interest after a while, and you get tired of listening to some of the other things. At the same time the Committee needs continuity. These are issues for which we don't have good guidelines. We make it up as we go along. But I think in a government, the more, first of all, that the public participates in the process and the more--the better the road map, the easier it is to govern with the consent of all who are being governed. That's what we're looking for.

CHAIRMAN CAPLAN: Okay. Unless there are any other questions about our membership and what to do to put people forward, why don't we take a 15-minute break? Then what I would propose is we come back and follow up on the issues raised by Dr. Satcher and Dr. Margolis in terms of hepatitis C lookback, notification, that area. Then I think we have some public comment to do, which I suspect is going to take us toward the values and principles issue about increasing efforts at safety relative to cost and practicality, which I know members of the Committee want to talk about, and that should get us up through lunch.

So let's plan on thinking about what we heard this morning, going to the lookback issue and notification and public awareness, and spend some time with that and then move on to the public testimony as a way to move us toward the consideration of continued efforts to push for safety.

DR. NIGHTINGALE: Could I have a show of hands about how many members of the Committee wish to make statements? One, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen.

CHAIRMAN CAPLAN: Well, forget it.

[Laughter.]

CHAIRMAN CAPLAN: Okay.

DR. NIGHTINGALE: On that note...

CHAIRMAN CAPLAN: We have time, so we will go there. Did you want to do that sort of pre-public testimony? You want to go around that way?

DR. NIGHTINGALE: Yes.

CHAIRMAN CAPLAN: All right. We'll do it that way. Maybe we'll get us into that and then move into the public testimony side after lunch, if that's how that's going to work. Okay.

[Recess.]

CHAIRMAN CAPLAN: Could we take our seats back here, please?

What I'd like to do is have the members of the committee spend whatever amount of time they want, but just a few minutes on the presentations we heard this morning on hepatitis C on the look-back. I know we've had discussions about, and requests about this matter of sending the letter. I understand that this is a subject under discussion, and has legal and even constitutional issues in play, but you may want to say a bit more about that in terms of advice to the Secretary.

One idea that I had which I can toss up in front of the committee is that we might want to say if something hasn't happened by a certain date, than we would hope that monies would be appropriated to make sure that something happens by another date, but that's just my particular thinking about letters.

But let me open the floor and see if, based upon the presentations, we have any discussion, comment that you want to make about the hepatitis C, the look-back, the notification issue.

One thing I think we might want to urge, if not recommend, is that there be, with acknowledgement to Dr. Nightingale's comment about intensity versus duration, some effort to coordinate the letter with CDC efforts, patient and foundation activities in private sector activities. It seems to me, whether you want to commit to an intense effort or make sure that something is there that's going to go on over time, it's just important to get the ducks lined up so that you get a maximum impact of sending the letter. Plus, if the Secretary--if you remember what he said, he said in part, we're not sure we're ready for a response that might be large, to sending out a letter. Other organizations and other groups need to be on board here in terms of knowing what's going on, being ready to both field questions, but also perhaps to bring pressure to bear to make sure that the infrastructure for an adequate response, if not right after the letter goes back, that at some point in the future is there. So that is of concern to me, that we try to push that they coordinate on this kind of thing, and that we urge everybody to try and work together, all the interested parties here. Jim?

DR. AuBUCHON: I certainly agree with you that coordination would appear to be helpful, although we have no data to know exactly what is going to work, and that is an unfortunate impediment, as Dr. Margolis identified, but even beyond coordination, I would urge the federal government to identify resources to put toward this problem.

If I could make a--what will probably be perceived as a cynical observation--when this committee began its existence several years ago, there was a great push on from the Congress that we had to address this hepatitis C problem immediately, and we have addressed it from a transfusion point of view, but as Dr. Epstein pointed out, that is a very small piece of the puzzle. The larger piece of the puzzles is not getting the attention and the resources it deserves. One might suggest that some in the federal government--and I do not mean those around this table--directed attention to hepatitis C through transfusion as a cheap means of addressing what they thought was the hepatitis C problem, because the federal government didn't have to pay for hepatitis C look-back, primarily. They foisted it off on someone else. I think it's time, and the situation deserves additional resources from the federal government to address the larger part of the problem.

CHAIRMAN CAPLAN: Fernando?

DR. GUERRA: I think as we continue to take the hepatitis C national effort to the scale, we need to somehow--and I'd be interested in Dr. Margolis's response--we need to build that onto the efforts that have been in place for HIV/AIDS, the national campaign, and not take away from that, because that continues to pose a very significant threat in communities.

CHAIRMAN CAPLAN: Well, perhaps we can come back after we listen to committee presentations up until the lunch period, to what we want to say, if anything, about both budget resource commitment and coordination in general. Since we've been around for the three years, I continue to find it somewhat surprising that the total budget to send out the letter is bigger than the CDC Hepatitis Office budget, but all right.

Okay. I guess the way to go on this, we have a lot of people who took the request for comment very seriously, and that's great, and I am now in the unfortunate position of trying to steer a group, in terms of time, that I have learned to be unruly about these matters. But I think we have a 5-minute aspiration on presentations and statements, and what I'd like to do, is instead of organizing us by height or alphabet or something, I'm going to start down with John over there. I tend to--these people have accused me of looking to the left first, so let me go over there, and then we'll just move right around the room for committee members to make their presentations. I didn't watch all the hands, so not everybody has one, but if you do have one, let's start there and just come down.

So, John, I give you the first 5-minute opportunity.

MR. WALSH: Thank you. I'm used to being at the end of the alphabet.

First of all, I'd like to express the appreciation on behalf of the alpha one community to this committee for taking the shortage situation with respect to A1PI products as seriously as we have. The Alpha One Foundation is dedicated to providing the leadership and resources that will result in increased research, improved health, and worldwide detection, and ultimately a cure for alpha one. AAT is a single-gene defect leading to loss of one serum protein, and there is currently only one product available, manufactured by one manufacturer, naturally, to provide augmentation therapy for patients with alpha one.

The resolutions that I would like to report on in the form of an update that helped us through a crisis that lasted some 24 months with supplies decreasing for allocation between 40 and 80 percent throughout our population.

On April 28, 1998, resolution: "The Department of Health and Human Services should explore, in collaboration with industry, health care providers and appropriate consumer groups, methods to optimize and standardize allocation of available products in an equitable manner, including management of emergency supplies and programs that distribute products directly from manufacturers to registered consumers."

This distribution issue was addressed by the Alpha One Association, the alpha one community, in conjunction with the foundation and the medical and scientific advisory panel. We did address it, and a direct distribution strategy was developed to respond to the request for direct consumer allocation, and deliver prolastin directly to the consumer. Prolastin is no longer sold to distributors. It is allocated directly from the manufacturer to the consumer, ensuring that the fully-prescribed dosage is available to each alpha as long as there's product available, which includes issues related to lot releases and ultimate supply issues.

Everyone enrolled in the program has received their full prescription at 28-day intervals, resolving the need for reduced dosages or increased intervals at this time. In addition, over 200 consumers that did not have access prior to November '99, are currently on augmentation therapy. So a controlled direct distribution in the case of a one-product-one-manufacturer community like ours has definitely resolved the inequities and directly related to decrease and severe shortages.

April 28, 1998, the committee made a recommendation that industry should explore with the FDA strategies for reallocating partially processed plasma materials from one manufacturer to another, you know, to optimize production of alpha₁-antitrypsin deficiency and other plasma derivatives.

We are able to work very closely with industry, and again, on behalf of the Alpha One community, I'd like to thank the American Red Cross and Baxter for working very closely with Bayer in a cooperative relationship that ultimately provided enough 401 paste to optimize production capacity at both of Bayer's manufacturing facilities.

So for now we have enough raw paste to produce at maximum capacity. That does not mean we're going to have enough end product or throughput to be able to satisfy demand.

April 28, 1998, again the NIH and industry should immediately evaluate alternative dosing schedules and alternative delivery systems for alpha one therapy, including prophylactics strategies and strategies for treatment during acute exacerbations of disease, and accelerate the development of gene-based products and gene-directed therapies for alpha one.

This definitely supported the evaluation of new delivery technologies. The advisory committee recommendations for expedited development of new and non-plasma derived options helped break the logjam for aerosol or inhaled development of A1PI, and we currently have three manufacturers that are in various processes of development for an aerosol product, including one transgenic product, will be the first recombinant product available to our community, potentially available to the community, obviously, pending trials and licensure, but it's already gone through a Phase I.

The current situation, with only one manufacturer and one product, with limited production capacity, it is inevitable that demand will exceed supply. In fact, I believe we're there right now, where we're going to see, within the next two months, the inability to be able to dispense 100 percent of prescribed dosages to patients, so we've already hit the wall in optimizing the distribution. We need another product. This will ultimately affect every consumer. The product will continue to be shipped in sequence with no prioritization given to reimbursement issues, which was one of the problems in our distribution that's corrected by this, effectively, or clinical triage. There's been no determination by medical and scientific advisory committee that clinical triage is possible, let alone appropriate in relationship to augmentation therapy for alpha one. It failed in Europe. The European Respiratory Society tried to implement one in 1999.

The future IV products--there are two IV products currently under different stages of development. One is finished the Phase III and delayed in PLA application for numerous reasons. The other is in Phase III now. It's fully recruited for enrollment in the trial and should be completed, and once their data is analyzed, will obviously get to the FDA for expedited licensure.

There are three initiatives, as I said, with respect to the aerosol delivery, which would--we hope, would make a more efficacious process to deliver the drug directly to the lung. It's hoped that aerosolized products will provide increased access to more consumers, being able to take care of up to five times as many consumers with the same raw material, and also be more cost effective.

The Alpha One Foundation will continue to work closely with industry and the FDA to promote the development of new therapies. Alpha One has a meeting scheduled with the FDA and CBER, which has been very cooperative in addressing the issues related to clinical trial design and the IND issues. One of the issues we're discussing is a recommendation to form a working group between the FDA, the NIH and the Alpha One Foundation Medical and Scientific Advisory Group, to be able to actually look at some of the surrogate marker endpoint issues and other impediments to design of clinical trials and approval of products.

And the foundation is organizing and HR CT scan, using high resolution CT scanning to look at the progression of lung disease as a potential surrogate marker, and also an animal model study workshop, which will be conducted in Sienna in Italy.

There's just a couple other comments that I would like to make to the committee. Regards HCFA, the committee's action, I think HCFA had more response to the outpatient prospective payment issues. The APC code change, where there would be a direct path to plasma derivatives, definitely made it possible so that all of our HCFA consumers would not be cut off from product and create a real problem for access. So we thank the committee for the support in that.

We've taken the responsibility to communicate directly with all of the distributors, all of the providers for HCFA treating alpha one patients, and let them know how to actually do the billing, and we're working closely with HCFA to accommodate that.

The transition to recombinant is a result of this committee's strong recommendation, although I notice that the--in the final recommendation that was published, it only mentioned hemophilia factor products. I believe the committee discussed that in the broader context of plasma derivatives, and I'd like to state for the record that I think that very much helped the PPL Therapeutics out of Scotland to focus their attention on alpha one, and not just cystic fibrosis.

Finally, I'd like to thank the members of this committee for their support for the Five Points of Life, speaking of donor awareness, and the Surgeon General's remarks earlier, the Five Points of Life event is to raise donor awareness for organ tissue, DNA, plasma pheresis, obviously, donations country-wide. Dr. Gilcher, his group has a rider involved with that program that raises a lot of awareness, and I think it's just a ripple and we need to do more, as much as possible, we're committed to. ARC, AABB, ABC and ABRA have all contributed to sponsor the event, and there will be an activity here in Washington, a reception for congress people. And even the insurance industry is involved. State Farm, I think, is the only one I'm aware of so far that's embraced this, but I think it's important for us all to take on the responsibility to get involved with creating more donor awareness.

I would also like to thank the organizer of the ride, Life South, for all their efforts, and to thank our committee's Executive Secretary, Dr. Steve Nightingale, for his ongoing participation and support throughout the process. Dr. Nightingale is actually riding the first week, from Bar Harbor, Maine to Boston, Massachusetts.

So again I thank the committee on behalf of our community, and look forward to making more progress in the future.

CHAIRMAN CAPLAN: Thank you. Unless it seems--I mean if someone--I'll take a minute to see if there's a question or a comment after each speaker, but you don't have to feel compelled to do so, comment or--that's a polite way of--

[Laughter.]

CHAIRMAN CAPLAN: All right. Jerry?

DR. WINKELSTEIN: Well, I was unprepared. I'm usually last alphabetically, so thank you very much.

Well, I wanted to make two comments. The first is in the form of a thank you, which is heartfelt, and the second is in the form of a proposal for a future agenda item.

Now, the first is a thank you, and if you will remember, one and two years ago I presented information to this committee when I was not on the committee, but a member of the audience, about the shortage of IV gamma globulin and the many patients with primary immune deficiency diseases. I'll remind you that well over 10,000 patients receive IV gamma globulin, and it is the only thing for primary immune deficient patients which is therapeutically beneficial. There's no substitute for the IV gamma globulin. But during the past few years there had been a very significant shortage of IVIG for these patients, which was impacting very significantly on their health status.

Now, the part of the thank you is that through the efforts of this committee, a similar committee advising the FDA, the Immune Deficiency Foundation, and under the leadership of Dr. Epstein, the FDA itself, all of these groups developed a realistic and achievable clinical protocols which will speed the licensing of new IV gamma globulin preparations from a number of old manufacturers and new manufacturers. One such protocol, my understanding is, nearing completion, if not been completed, from the patients' point of view at least. Another clinical protocol has begun to enter patients over this summer, and two other manufacturers are developing clinical protocols as we speak. I believe that the availability of these new preparations will help very significant in alleviating the shortage. So my thank you is that I would like to publicly thank both this committee and the FDA for their efforts to alleviate the shortage. I do believe it made a difference, and I think we're seeing the results of that even as I speak. So if you ask yourself if the committee has done anything worthwhile, which I had to ask myself before I joined the committee, rather than sit around, I can give you evidence that you made a significant difference for these patients.

Now, my second point relates to asking your advice as to whether or not there should be consideration for a new agenda item over the next number of months or year, and I'd like you to consider whether this is an appropriate agenda item. Now, as you know, patients with primary immune deficiency diseases are the only long-term users of IV gamma globulin, one of the plasma products. Many of the patients have been on for decades. In fact, there are patients entering their third decade of use of licensed IV gamma globulin in this country, and most of them will remain on IV gamma globulin for a period of four, five or six decades if the therapy is as good as we think it is. From that point of view they're quite unique, and represent, if you will, a canary population for patients receiving IV gamma globulin and many other disease states in the short term. These long-term patients receive it for decades, as I said.

Now, in recent years, there's been a growing suspicion that long-term consequences have not been well documented. There are at least two articles of anecdotal case reports of patients with primary immune deficiency disease, who have received IV gamma globulin, presenting with unexplained central nervous system diseases. In addition, there are some other problems associated with the use of this material, as there would be with any pharmacologic or biologic material. Renal disease, immediate adverse events, and the consequence of long-term use have been looked at, but not in a formal way.

And so what I'm wondering is whether or not this committee should consider adding a future agenda item which would include presentations on the value of a formal assessment or prospective study of the long-term and short-term adverse effects of IVIG. Obviously, I would hope then that they would endorse such studies because these studies are not being done currently. Whether that's a role for this committee or not, I'm young on the committee, and so I'm not sure, but I did want to bring it to your attention.

CHAIRMAN CAPLAN: Thank you.

DR. NIGHTINGALE: I would comment briefly that there are many ways to view the role of the committee and many readings that you can make of the charter, but one that I think that would encompass not only your statement but the statements that I anticipate from the other side of the room here, would be that this committee very fundamentally addresses what economists call externalities. For those of you who are not either economists or children of same--and I am in category B--and externality is a cost of producing a good or product that the market for one reason or another does not recognize. So I think I've answered your question constructively.

DR. WINKELSTEIN: Then my impression would be that this would be an appropriate agenda item, depending on priorities of the committee.

CHAIRMAN CAPLAN: Jane.

DR. PILIAVIN: I was under the impression that our remarks were supposed to be addressed to the precautionary principle. So of course, as soon as I start to talk, my voice acts up. And I guess I'd like to start by referring to the article that you included in our voluminous materials for this meeting, entitled, "Will Blood Transfusion Ever Be Safe Enough?"

And that's the point that I guess my remarks are all oriented around that. Whether that puts me on the left or on the right, I don't know, because I don't know where that dimension goes from to. I also want to note that we were just handed out a bunch of new stuff, one of which is a memo from Merlyn Sayers about leuko-reduction, which just ties in with this same issue.

First I want to say that I read everything you gave us about the precautionary principle and I still don't know what it is. That's because very early on in the material it says that it's not going to give a definition of it, and then as you read the examples, clearly, the precautionary principle goes everywhere from saying if something has any kind of potential harm to the environment, to human health, you shouldn't do it, to a very basic kind of risk cost benefit analysis on the other hand, that says when it comes to new technological things, you should be really, really careful and think about the concerns for human health. So I don't know what the precautionary principle is.

I think we all have been trying to be careful, and if the precautionary principle says "Be careful", then we've been following it. I get the sense that because of the examples they use about the European community, there's more attention in regard to this principle to new developments than to long-standing situations, and I'm wondering whether that's appropriate. Is it only about new technological things or is it about any kind of dangers? And I'm going to deal with it more as if it's any kind of dangers.

Okay. I kind of liked one of the things I read in here which said that when dealing with data under the precautionary principle, you need less than a preponderance but more than a scintilla of evidence of harm. I just love the word "scintilla" anyway. And I'm wondering to what extent we in the past and other committees have been dealing with scintillas or less rather than with preponderances, and that we should take that into account. I'm specifically referring to the NBCJD issue, which strikes me as having less than a scintilla of evidence. As you all know, I have been opposed to that regulation regarding people who have been in Great Britain.

Also in the materials on the precautionary principle, one of the things that they said--and this was clear--is that you should deal comparably with things, that you should not have one sort of reaction to one problem and a different kind of reaction to another problem, that things should be dealt with in some equitable kind of way. And again, referring to the response to NBCJD, I would like to ask why did we respond that way to that issue and have not responded to what struck me as more evidence about Chagas Disease, and certainly lots more evidence about problems with errors, simply blood matching and other kinds of errors. Now, these--I mean, the latter is of course not technological in the usual sense and it's not new, but if we're going to apply this principle to concerns about risk, I think we have to look at having comparable responses to issues, and certainly there are far more people who die from errors of the sort we talked about last time than have, obviously, NBCJD--nobody's died--and Chagas Disease, I don't think anybody's died from transmission, and certainly there's all sorts of things that could come down the pike.

In terms of equity issues of a different sort--no, I think I'm going to skip over that because I know I don't have that much time here.

I want to get back on my usual hobby horse of safety equals availability. At the level of infectivity that we now have in the blood supply, the idea of adding leukocyte depletion and individual NAT testing strike me as inappropriate use of money for a variety of reasons. Of course it's going to drive the price up, which will lead to both a decrease in the number of people who can afford the product, and a decrease in money that's available for other things. Certainly it will lead to an increase in medical premiums. It will put an excessive drain on the public funding, Medicare, Medicaid, and from what I saw in terms of the estimated dollars per year of quality adjusted life that will be added by the individual NAT testing, this struck me as really inappropriate use of money.

I want to think, in terms of other uses of money and how much life could be saved, things of the sort of child immunization, sex education and HIV prevention, prenatal care, visiting nurse programs and even cancer research, and certainly putting in funds for getting more information to more people about Hepatitis C would come under better uses of money.

In regard to availability then, these things also have the imp