Blood Safety Transcripts

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

Eighteenth Meeting

"Prioritizing Decisions in Transfusion Medicine: Transfusion Transmissible Diseases."

8:33 a.m.
Thursday, January 23, 2003

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

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

Committee Members

• Mark Brecher, M.D., Chairman
• Larry Allen
• Celso Bianco, M.D.
• Richard Davey, M.D.
• Ronald Gilcher, M.D.
• Edward D. Gomperts, M.D.
• Paul F. Haas, Ph.D.
• W. Keith Hoots, M.D.
• Dana Kuhn, Ph.D.
• Jeanne Linden, M.D.
• Lola Lopes, Ph.D.
• Gargi Pahuja
• John Penner, M.D.
• Mark Skinner, J.D.
• John Walsh

Non-Voting Government Representatives

• Mary E. Chamberland, M.D.
• Jay Epstein, M.D.
• Colonel G. Michael Fitzpatrick

Consultants to the Committee

• Christopher Healey, J.D.
• Captain Lawrence McMurtry

C O N T E N T S

AGENDA ITEM PAGE

• Call to Order, Introduction of Members, Conflict of Interest 4
• Review of Original Institute of Medicine report- Paul McCurdy 18
• Introduction and review of prior ACBSA recommendations - Mark Brecher, Chair 28
• Break
• Ethical Considerations of Medical Deciions - Jonathan Moreno 87
• Remarks Regarding the Committee Charter - Eve Slater 125
• Lunch
• Putting Risk in Perspective
• Overview of Viral Risks and Critical Issues of NAT screening - Michael Busch 135
• CDC Update on West Nile Virus - Mary Chamberland 184
• Procleix NAT Testing Platform - Neil Gunn 218
• Roche Platform NAT Testing - Paul Chapman 247
• NAT Testing for Source Plasma - Gerold Zerlath 259
• Prioritizing Risk in Transfusion Medicine - James AuBuchon 276
• Committee Discussion 310
• Adjournment 324

P R O C E E D I N G S

DR. BRECHER: Everyone please take their seats. We would like to begin.

I would like to welcome everyone to the 18th Meeting of the Advisory Committee on Blood Safety and Availability. I'm going to work hard to keep this on time. There was an agenda that's available in members' packages, and we're going to try to stick to that, although we're going to do a couple flip-flops of speakers.

We're going to have a roll call and a conflict of interest which is going to be reviewed by Mac McMurtry.

CAPTAIN McMURTRY: Let's do the roll call first. Larry Allen?

[No response.]

CAPTAIN McMURTRY: Celso Bianco?

DR. BIANCO: Here.

CAPTAIN McMURTRY: Mark Brecher's here. Rajen Dalal called last night, said he's not going to be able to come.

Rick Davey?

DR. DAVEY: Here.

CAPTAIN McMURTRY: Ron Gilcher?

DR. GILCHER: Here.

CAPTAIN McMURTRY: Ed Gomperts?

DR. GOMPERTS: Here.

CAPTAIN McMURTRY: Paul Haas?

DR. HAAS: Here.

CAPTAIN McMURTRY: Chris Healey?

MR. HEALEY: Here.

CAPTAIN McMURTRY: Keith Hoots?

DR. HOOTS: Here.

CAPTAIN McMURTRY: Harvey Klein is not here yet.

Dana Kuhn?

DR. KUHN: Here.

CAPTAIN McMURTRY: Jean Linden?

DR. LINDEN: Here.

CAPTAIN McMURTRY: Karen Lipton is with the AABB Board of Directors.

Lola Lopes?

DR. LOPES: Here.

CAPTAIN McMURTRY: Gargi Pahuja?

MS. PAHUJA: Here.

CAPTAIN McMURTRY: John Penner?

DR. PENNER: Here.

CAPTAIN McMURTRY: Mark Skinner?

MR. SKINNER: Here.

CAPTAIN McMURTRY: John Walsh?

MR. WALSH: Here.

CAPTAIN McMURTRY: And Dr. Winklestein called, and he's not going to make it today.

Next is the new and approved ethics statement. I'd like for all of you to settle back and get comfortable, take a deep breath.

Ethics rules for Committee members appointed to Federal Advisory Committees as special government employees. The Ethics Division of the Office of General Counsel has asked that I explain the rules that apply to you as special government employees or SGEs. If you have any questions, let me know. I'll seek assistance from the attorneys in the Office of General Counsel. All matters I'll be discussing are explained in more detail in a handout that I will provide to you, but haven't yet.

Pursuant to several sections of the Public Health Service Act, as amended by the U.S. Code and various provisions of the Federal Food Drug and Cosmetic Act, the Secretary of the United States Department of Health and Human Services has authority to carry out research in health fields including diseases involving blood and blood products, and for issuing and enforcing regulations concerning the collection, preparation and distribution of blood and blood products. The Advisory Committee for Blood Safety and Availability will advise, assist, consult with, and make recommendation to the Secretary and the Assistant Secretary of Health regarding these broad responsibilities.

The Chair and other members are special government employees, appointed to perform duties on an intermittent basis not to exceed 130 days during any 365-day period. I have the U.S. Code reference for this authority if anybody would like to see it.

All Committee members appointed as SGEs are required under the Ethics in Government Act, amended by the Ethics Reform Act of 1989 to file a financial disclosure report when first appointed and annually thereafter. The information reported is used to determine the matters for which a Committee member must be disqualified under the Criminal Conflict of Interest Statutes.

Let me discuss the Criminal Ethics Statutes here for a second. SGEs are subject to a number of criminal ethics statutes. Violation of the bribery provision imposes substantial fines and/or imprisonment. A violation of any of the other U.S. Code provisions is punishable as a Class A misdemeanor, and subject to fine and imprisonment. Willful violation of the Code elevates the commission to a felony, and the Attorney General may opt for several penalties.

In a civil action the government need only prove the violation by a preponderance of the evidence rather than by the criminal standard requiring proof beyond a reasonable doubt.

I need to describe these various statutes. First is a bribery statute which prohibits Federal employees, including SGEs, from seeking, accepting or agreeing to receive anything of value in return for being influenced in the performance of an official act. There is the example of a person receiving a brown paper bag of money in exchange for recommending to the Secretary.

There is the Anti-Representation Statute, which prohibits an SGE from receiving compensation for representational services rendered by the employee or another person before HHS or another Federal agency or other specified entity such as a court or committee in any particular matter involving a specific person (1) in which the SGE has participated personally and substantially as a government employee, or (2) which is pending in a government agency in which the SGE is serving if the SGE has served more than 60 days during the immediately preceding 365 days.

The Post Employment Statute imposes a lifetime ban on a former SGE from representing another person or entity to HHS or other Federal agency or other specified entity such as a court in any particular matter involving a specific party in which the former SGE participated personally and substantially while serving in the government.

The Financial Conflict of Interest Statute, the main Conflict of Interest Statute, prohibits an SGE from participating personally and substantially in any particular matter that could affect the financial interest of the SGE, the SGE's spouse, minor child, general partner, and organization in which the SGE serves as an officer, director, trustee, general partner or employee, or an organization with which the SGE is negotiating or with which the SGE has an arrangement for prospective employment. Specifically, you as an SGE cannot work on matters affecting your financial interest or those of your spouse, minor children or organization with which you are affiliated.

An example would be owning stock in pharmaceutical company X which produces a test for viral contamination. You cannot participate in decisions or discussions to partner with company X to promote that test.

You must also disqualify from matters affecting your financial interest as a class. For example, the same scenario, you own stock in a pharmaceutical company that produces a test for viral contamination. You cannot participate in decisions regarding testing for viral contamination. However, broad matters of national policy that don't focus on a specific industry are not a problem.

Under regulatory waiver issued by the Office of General Ethics, you may participate in matters affecting your employees a matter of a class, but not in a manner that will affect the employee specifically. For example, you may recommend a grant program be established even though the university for which you work will be eligible, but you may not participate in consideration of a specific grant application submitted by your university.

Additionally, while this exemption will allow you to participate in any matter of general applicability that would affect the financial interest of a specific, we'll say Harvard Medical School and/or Harvard University as a member of a discreet and identifiable class of similarly situated medical schools or universities. The exemption will not protect you from violation of the criminal statute if the matter will have a special or distinct effect on Harvard Medical School or Harvard University. This means that you can participate in generally applicable matters such as legislation, regulation or policy that affects medical schools or university as a class. The same rule applies with respect to other types of employers, so that if you work for a pharmaceutical company, you can participate in matters affecting your employer as a member of a class. However, if you have any other interest besides employment, such as stockholding, you must disqualify from all matters, even if it only affects that employer as part of an industry sector.

On the other hand, another regulatory exemption, if you're under another regulatory exemption, if your financial interest is in publicly traded securities valued at less than $25,000, you can work on matters affecting as part of industry sector. But again, you have to avoid matters that will have a specific effect on that company.

You may receive compensation for speaking engagements, or writing undertaken in a personal capacity. However, you may not receive compensation for speaking or writing that was undertaken as part of your official duties as a member of the committee that draws on nonpublic information to which you have access as a member of the committee, nor if the invitation was extended primarily because of your membership on the committee. You may receive gifts where circumstances make it clear that the gift was not offered as a result of your membership on the committee.

Generally you should not use your position to imply that the Committee or the government endorses your private activities. You should not disclose nonpublic information to which you have access. You may state your personal opinions, but should not imply that you were speaking for the Committee unless you are actually authorized to do so.

There is an issue regarding fund raising. You may do personal, charitable fund raising, but you may not personally solicit funds from someone who has business before the Committee. Under the Constitution. While you serve as an SGE, you may not have an employment relationship with a foreign government. That is, you can't be reimbursed by a foreign government. This may include foreign public universities and government owned companies, depending on the degree of control the foreign government exercises. Under the Foreign Gifts and Declarations Act, you generally may not accept gifts from a foreign government unless the worth is under $260.

In your official capacity or as a group, Committee members are prohibited from engaging in any activity which directly or indirectly encourages or directs any person or organization to lobby one or more members of Congress. When authorized, Committee members may appear before any individual or group for the purpose of informing or education of the public about a particular policy or legislative proposal. Committee members may also communicate to members of Congress at the request of any representative or senator. Communications to members of Congress initiated by Committee members in their official capacity as members of the Committee, should be coordinated through the Office of the Assistant Secretary for Legislation.

As private citizens Committee members may express their personal views, but not the view of the Committee as a whole or the opinions of HHS to anyone. In so doing, Committee members may state their affiliation with the Committee, may factually state the Committee's official position on the matter to the extent that nonpublic information is not used, but may not take new positions and represent those views as the Committee's position on the matter. Moreover, in expressing their private views, as will all other personal nongovernment activities, Committee members are not permitted to us government computers, copiers, telephones, letterhead, staff resources or other appropriated funds. All personal activities must occur off-duty time.

And finally, the Hatch Act prescribes that restrictions on certain political activities of Federal employees. Unlike the criminal statutes and most other ethics rules, which are fully applicable to an SGE throughout your entire term of appointment, the Hatch Act restrictions apply only during the period of any day in which you are actually performing government duties. For example, if an SGE attends an Advisory Committee meeting from 8 to 1, and at 3 o'clock the--if you attend the meeting during the day, the SGE may attend a political fund raiser or even solicit political contributions after they leave the Committee meeting that day.

That's it. Thank you.

DR. BRECHER: That was enough, Mac.

[Laughter.]

CAPTAIN McMURTRY: Well, I tried to get us off to a flying start.

DR. BRECHER: All right, thanks.

The purpose of this meeting is to review prioritizing decisions in transfusion medicine, and we're going to use transfusion-transmitted diseases as a take-up point for our discussions, but before we get into the meat of that, most of this morning is going to be going over some background material for the Committee, why we have this Committee, where we've been before, and what has the Committee accomplished.

So to start that off, and for those of you who have the agenda, I flipped the first two speakers. And so we're going to review the original Institute of Medicine report which led to the creation of this Committee, and Paul McCurdy is going to do that. And there is a copy of a transfusion article in the Committee members' packages that summarize the IOM report.

Paul?

DR. McCURDY: I gather they have the Executive Summary of the report; is that what you referred to, Mark?

DR. BRECHER: Yes, that's essentially what they have.

DR. McCURDY: I think Mac forgot one item, and that is, pay attention under penalty of law.

[Laughter.]

DR. McCURDY: Mr. Chairman, Committee members and guests, I'd like to thank the organizers for inviting me to present today on some of the activities surrounding the genesis of this Committee. When you get old enough, you are considered a historian, I guess, and maybe you remember these things and can talk about them.

This report that's entitled on the screen here, "HIV and the Blood Supply: An Analysis of Crisis Decision Making," was a major factor in the genesis of this Committee. As you will see, there were other factors, most notably activities of the Committee on Oversight of the Congress of the United States that played a major role.

In 1993 Senators Kennedy and Graham and Congressman Porter Gross asked Dr. Shalala, who was then the Secretary of DHHS, to review the government's role in the matters that led to the infection of patients with hemophilia and blood transfusion, following blood transfusion, their infection with HIV in the early '80s. Dr. Shalala responded by commissioning the IOM to do this study.

The report was released in July 13th, 1995. I well remember a late afternoon briefing for some members of the administration, and I was privileged to be one of the representatives of NIH that attended that briefing one or two days before the release of this report. It was highly critical of PHS leadership in failing to override long-standing blood bank conservatism. There was discussion using core antibody for hepatitis B as a surrogate test for HIV. There were very limited data in 1983 to lead to that, but in retrospect--the retrospectoscope is an excellent instrument--in retrospect it would have been a good test.

Anyhow, there was concern expressed that changes in recruiting donors, in asking questions of donors, would lead to shortages and patients would die for lack of blood. There was also discussion that changes would be too costly and who would pay.

I sat on the sidelines during this--some of these discussions, and I think that many of the people involved did remarkably well with what they had to work with. But nevertheless, they were criticized because of the alleged limited public health response.

Nevertheless, Dr. Shalala, when she received the report, despite its many faults, had a public relations press release that accepted the report and its recommendations except for a compensation plan which was mentioned in the report and has essentially disappeared.

One of the things that happened was a task force was put together to implement the recommendations of the Committee. This rapidly became the Internal Blood Safety Committee, which was not recommended by the IOM report, but it was in keeping with its goals. That comprised of the directors of CDC, NIH and the FDA Commissioner, and they often brought people to the meeting with them when these--when various matters were discussed.

The acceptance of the report was reiterated at a meeting of the Subcommittee on Government Reform, who held a hearing on October 12th, 1995. This is one of the few committees in Congress that has individuals testifying under oath, and hence what they say carries perhaps a little more weight, and they can be held responsible for it. It's a little different than many of the other committees of the Congress.

The first recommendation was that the Secretary appoint a Blood Safety Director at a very high level, and Dr. Phillip Lee was appointed the first Blood Safety Director. At that time he was the Assistant Secretary for Health, and most commonly, that office has been filled by the Assistant Secretary for Health. And he chaired the Internal Blood Safety Committee.

The Internal Blood Safety Committee began by meeting fairly frequently, but now meets essentially on call when an item seems to be of sufficient import to take it to that level.

The second recommendation which is most pertinent perhaps to this committee, was a recommendation for what they call the Blood Safety Council, but this now has metamorphosed to the Advisory Committee on Blood Safety and Availability. It was meant to report to the Secretary through the Blood Safety Director, and advise on global public health service issues, and differed in that fashion from BPAC.

In you handout you'll find that the Blood Safety Council--and this is a quote--was "to assess current and potential future threats to the blood supply; to propose strategies for overcoming these threats"--this is the recommendation now of the IOM--"to evaluate the responses of PHS to these proposals; and to monitor the implementation of these strategies."

The Council should alert scientists. The Council should alert scientists about opportunities and needs for research to maximize the safety of the blood supply, and it should take the lead to ensure the education of public health officials, clinicians and the public about the nature of threats to the blood supply and the public health strategies dealing with these threats.

Now, the congressional subcommittee that I mentioned previously, the Subcommittee on Human Resources of the Government Oversight and Reform Committee was chaired by Congressman Shays, and there was a great deal of interaction between his committee and DHHS staff. The congressional committee actually undertook a long-term, four or five-year period of continued careful oversight of what the Federal Government and the PHS was doing in the way of blood safety.

The charter of the Committee, which is how it operated for the first, I guess, six or eight years of its activity, the charter was molded with the help of this Committee and the high-level echelons in DHHS. The initial charter was to advise the Secretary, via the Blood Safety Director, on the implications of economic factors on blood safety and availability, define public health factors that have an effect on safety and availability, and also advise on broad public health, ethical and legal issues related to blood safety.

This is a very broad charter. I think the Committee has done much of this, but I don't know that it's done it all. The most important thing is that it is advisory in that the government can take its recommendations and do or not do what they think is appropriate.

There was a lot of discussion about this Blood Safety Committee. There was a considerable delay, as is often the case in government I getting it off the ground, but there was one meeting where Phil Lee set a deadline for the first meeting, which was not made--we came close--asked that NIH run the meeting, that the FDA handle appointing the members of the Committee and CDC to pay for it. That as a rather three-headed animal that was a little hard to manage. With the efforts of a number of people, including my secretary at the time at NIH, the meeting came off. The first agenda item, which was near and dear to the heart of the congressional committee was hepatitis look-back. There were several other meetings subsequently that dealt with that, and there was another item, CJD and variant CJD as a potential threat to the blood supply, was given as an informational item to the Committee.

Now, there were several simultaneous things that went on about that time. They were not very--from my perspective--not very important, didn't have a great impact on what was going on, and did not ultimately, as far as I know, have much to do with this Committee. But it is of some interest that there was a forum on blood safety and availability convened by the IOM and supported by public and private sector organizations. It was mainly for discussion in a nonthreatening environment. It could not give advice. The FDA was one of the supporters of this group, and it had to be chartered as an advisory committee if it was going to advise.

It put forth three books over 21 months, and I think many parts of those book published in the middle '90s are still pertinent. This is a list of the organizations that supported this forum which lasted about a year and a half, and examples of subjects of blood bank regulation, blood banking and regulations, innovations and alternatives and regulation, and congressional oversight. There wa a book that deal with blood donors and the supply, spoke about enhancing collections, and of great interest to me at the time, perishable logistics. A member of a supermarket managerial staff talked about how they managed seafood in their supermarket chain around the country, and some of this is, I think, quite pertinent to the management of blood. There was also a booklet on blood and blood product safety and risk, and as I said, some of these are worth looking at.

I thank you.

DR. BRECHER: Jay? Committee members will you please identify yourselves for the transcript?

DR. EPSTEIN: Sure. Jay Epstein, FDA.

Thank you for the very nice summary, Paul, and it brings back memories to me too. One memory though that I have is that there was a lot of overlap between recommendation two, about establishing a blood safety council, and recommendation 13, about convening a standard expert panel, and my recollection, faulty as it may be, is that what happened is that the Blood Safety Committee looked at those two recommendations, tried to sort out which of the functions belonged within government and which were more properly advisory and oriented toward public process, and it's on that basis that the respective roles and functions of the blood safety committee within government and this advisory committee were crafted.

So it's not purely that the recommendations under number two are the basis for the charter of this advisory committee. It was a little bit of mix and match.

DR. McCURDY: You're absolutely right, and there was a lot of discussion with the congressional subcommittee staff that tried to formulate how the committee should, this committee should operate. I appreciate your better memory than I, in some of the areas at least.

DR. BRECHER: Other questions or comments?

[No response.]

DR. BRECHER: If not, thank you, Paul. That was very helpful.

We're going to move on to a review of the Committee recommendations. And I had asked Mac to pull together a grid of all the prior recommendations and the current status of what has happened with those recommendations through the years, and they are in the Committee members' package. Now, this is a rough draft, and we welcome input from members and others who know the impact of these recommendations that may have gone beyond the government, and so--I know there are a few typos in here as well. We'll capture those.

This is a long document, and we only scheduled an hour and it's going to be somewhat dry, but we're going to try to very quickly run through this document.

So as Paul originally outlined, that the Committee initially began its work on hepatitis C in 1997, and the initial recommendations were that the Committee recommended that a program to educate providers in medical care regarding the importance of identification of persons at risk of HCV, including those who received blood or blood products prior to '92, and appropriate measures for prevention, counseling, diagnosis and treatment. Two, that there would be an aggressive and sensitive public education campaign to notify test recipients prior to '92, and that there be a targeted look-back program triggered by donors that were detected as HCV, and there were three stipulations that went with that.

In terms of the action, the FDA issued its guidance supplemental testing notification of consignees of donor test results for antibody to hepatitis C for March 20th of, I believe it was '98. It was withdrawn on September 8th, following further Committee recommendations, and a new guidance was issued on June 17th, 1999.

Anybody have anything to add from that committee recommendations?

[No response.]

DR. BRECHER: If not, the next meeting was January 30th, 1998. At that time the Committee addressed emerging transmissible spongiform encephalopathies. The report made special reference--I'm sorry--the Committee recommended the Public Health Service coordinate an effort, develop a report within six months that would include references to food borne transmission, particularly through consumption of central nervous system tissues, iatrogenic transmission and transmission through blood components and plasma derivatives. A BSE action plan was developed and adopted by the Department in 2001.

The Committee further recommended the Public Health Service, professional groups and patient advocates emphasize the importance of post mortem exam to the protection of the public health. They supported the training physicians to recognize new pathological patterns or emerging disease in autopsy tissues, and it is now common practice to screen suspected deaths by autopsy for variant CJD. The Committee recommended nationwide standardization of procedures for screening donors at risk for transmissible spongiform encephalopathies, and the FDA developed guidelines for screening donors at risk for TSEs.

The Committee recommended the NIH specify its need for research and infrastructure support necessary to promote research on the TSEs with particular reference to animal testing that can discriminate among these conditions within each species. And this was done. And I think this is, as an overview, one of the successes of this Committee, is we've identified areas that needed further research, and largely that has happened.

The Committee recommended that during the next year the FDA worked with the industry and consumer groups to relax current Jakob Creutzfeldt disease guidelines on quarantine and withdrawal of blood products to the extent necessary to relieve shortages. This particular recommendation was rejected.

MR. HEALEY: Mr. Chairman, just a point of clarification. Is the purpose of this exercise to just reach consensus among the Committee members about the status of the action?

DR. BRECHER: Right. I'd like to make this as accurate a document as possible, and then with the Committee's agreement we would then post it on the Web as part of the Committee's site to basically illustrate what the Committee has done. This is actually a charge from an earlier Committee didn't ever seem to happen.

MR. HEALEY: So we should be reviewing this with an eye toward whether we agree with the current status, and provide you any feedback whether we think it's accurate or not.

DR. BRECHER: That's correct.

Jay?

DR. EPSTEIN: If that's the task, Mark, I think we're not in a position to vote at this meeting, that we have to take this back and look very carefully, because there are addenda and corrections that I see. For example, the matter most recently stated, it's true that we have continued to recommend withdraw of components. However, we did adopt a recommendation to discontinue the withdrawal of plasma derivatives in the case that at-risk donor was found to have contributed to the pool for fractionation. So, you know, there are some subtle, you know, clarifications that are needed, and on a cursory reading I think that's true throughout the document.

DR. BRECHER: I think that's a good point. So what I propose we do is we just briefly roll through what we have here with the caveat that we know there are going to be a lot of changes and you have to take it back. If you could funnel all those changes to Mac, and then we'll put it together, and then we will redistribute it by e-mail to the Committee members for their blessing, once we have put it all together, with a short-range goal that maybe within a month we could have all the comments back, a month after this meeting.

April 28th, 1998, recommendations for the short term. The FDA, the International Plasma Producers Industry Association, individual manufacturers and distributors of plasma derivatives and recombinant analogs, should on a monthly basis collect and disseminate standard information on production, distribution and demand for intravenous immunoglobulin, clotting factors, and alpha1-antitrypsin. And the PPTA since 1998 has been distributing this information.

Two. The Department of Health and Human Services, should explore in collaboration with the 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, and distribute the products directly from manufacturers to registered consumers. Emergency allocations of IVIG and direct distribution of alpha1-antitrypsin programs were established through direct collaboration between consumer groups and the industry.

Three. Industry should discuss triage for specific plasma derivatives, specific patient groups with the FDA, and the Federal Trade Commission Healthcare Providers and appropriate consumer groups, to promote accountability to the public. Most programs were set up at the local level. The FDA did issue a "Dear Doctor" letter on the issue, and articles appeared in professional journals addressing this subject. It was further recommended that the industry should explore with the FDA the possibility of importing additional supplies of intravenous and intramuscular immunoglobulin. Discussions continue, and the FDA did hold a workshop on clinical comparability in October of 2000.

Five. The industry should explore with the FDA strategies for reallocating process plasma materials from one manufacturer to another, and this has occurred.

The industry should explore with the FDA labeling and disclosure strategies in which to increase product availability without compromising public safety. The FDA has addressed this issue, and pretty much remedied the situation.

Seven. The industry and government should explore the impact of a temporary decrease I exportation of derivatives while they are in short supply in the U.S. This one was received by the Department, but I believe it was basically no action.

And the long-term recommendations were that every effort should be made to make recombinant clotting factors available to all who would benefit from them, and all barriers to conversion from human to recombinant clotting factors should be removed, and this has largely been accomplished.

MR. HEALEY: Mark, would this be an appropriate time to comment on that?

DR. BRECHER: It's a good time, Chris.

MR. HEALEY: I mean I can tell you it's our impression, and perhaps those in the hemophilia community can speak better to this, but I think the impression is that this hasn't been adequately accomplished and that indeed there's some more work to be done.

MR. SKINNER: Mr. Chairman, it would be my intent--and I'll mention it now and you can decide the appropriate point in the meeting to bring it up, but I concur with what Chris has said. The National Hemophilia Foundation and others in the bleeding disorders community have been greatly concerned recently about the backsliding, particularly since the shortages of the last couple years in terms of recombinant clotting factor availability, and in fact, we're now seeing that some of the states, in light of their budget crunches are actually going backwards and beginning to try to transition the population back to plasma-based therapies from recombinant therapies, and restricting choices in treatments.

And what I would like to propose is that Committee adopt yet another recommendation reaffirming its position and putting it in context of some antiquated Medicare guidelines which the states are using to justify this, which speak to things such as heat-treated and non-heat-treated factor, which is not even current nomenclature. And so we've been word crafting a resolution that whenever it's appropriate we'll bring forward and ask the Committee to look at it again, hopefully with the intent of adopting at this meeting so it can be useful I this state legislative cycle.

DR. BRECHER: I think we can do that, and when we get to making our resolutions for that, that will be one of those that we will discuss.

Two. The NIH was asked to convene a consensus conference on the use of recombinant clotting factors. This was referred back to the Committee, which considered the issue again in its August '98 meeting, which we'll come to in just a minute.

Three. The industry should explore strategies for development of reserves of plasma derivatives and their allocation during shortages, and this was accomplished.

Four. The NIH should immediately evaluate alternative dosing schedules and alternative delivery systems for alpha1-antitrypsin therapy, including prophylaxis and strategies for treatment during acute exacerbation, and accelerate development of gene-based product and gene-directed therapies for alpha1-antitrypsin. Those scheduled trials have been limited by the availability of product. Investigation of alternate delivery systems continues, as does investigation of gene-based therapies.

Five. The NIH should support the continued evaluation of the use and appropriate dose of intravenous immunoglobulins for indication where it benefits, and similarly, dose trials have been limited by availability, and there was that clinical comparability workshop from the FDA in October of 2000.

Six. The industry should work with the FDA to expand capacity sufficient to meet anticipated demand for plasma derivatives, and industry members have announced plans to expand capacity.

And industry and government should jointly explore the antitrust implication of efforts to share data in order to prevent shortages. This was done to some extent, but there was some concern however in the question of the projection of demand.

In August of '98 the Advisory Committee recommended that HHS take steps to accelerate the transition from plasma derivatives to the recombinant analogs. This is very similar to what we already discussed a few minutes ago. The Advisory also recommended that HHS support research, develop alternatives to plasma-based technologies for other diseases, such as immunodeficiencies, alpha1-antitrypsin and von Willenbrand's disease, and this research does continue to be supported.

The Advisory Committee recommends that the Department of HHS maintain, and as necessary, expand or intensify surveillance of blood donors and recipients for existing and emerging transmissible diseases. And this is an ongoing issue that is frequently addressed by the Department and also specifically by this Committee.

The Advisory Committee directs its staff to develop options to be presented to the Blood Safety Director for the creation of a sentinel system to monitor production, demand and utilization of blood products, and to create projections for future demand. I think it's fair to say that several systems have been in development or operating within a department, and studies are under way to improve the effectiveness of this monitoring.

Five. The Advisory Committee recommends that the Secretary of Health and Human Services direct the Healthcare Financing Administration and other appropriate agencies to explore strategies to ensure that all patients have access to adequate reimbursement for recombinant technologies and report to this committee in a timely manner. Discussion over reimbursement issues continue at many levels. Reimbursement for outpatient use of plasma derivatives was specified in the April 7, 2000 HCFA final rule on hospital outpatient and prospective payment systems.

The Advisory Committee recommended the secretary examine innovative responses, including regulating the import and export of plasma and finished products in order to ensure a safe and adequate supply of plasma derivatives and recombinant products for American use.

The Advisory Committee encouraged further efforts to develop and communicate standards for the prophylactic and therapeutic use of clotting factors and other blood derivatives. And clinical trials are needed, and they're dependent on particular product and availability, and the Department remains receptive to such initiatives. There is a typo here. This number 7 was duplicated/

The Advisory Committee urges the Secretary to convene a meeting of manufacturers of plasma derivatives and their recombinant analogs, to discuss strategies for distribution in light of shortage. Action on this particular recommendation was deferred as it was thought that it might be anti-competitive.

November '98. The Secretary of HHS, she recommended legislation that would lower barriers to the use of Federal databases for locating individuals at risk of hep-C. This particular recommendation was received by the Department, but no specific action was taken.

The Department of HHS should allocate sufficient additional resources to permit the CDC to work with state and local health departments to facilitate education, testing and referral programs for individuals at risk of hep-C, and in the fiscal year 2000, CDC budgeted $12.9 million for hepatitis C activities.

HHS should investigate supplemental sources of financial support to facilitate prompt completion of targeted lookback for individuals at risk of transfusion transmitted hep-C. Discussion of reimbursement issues continue at many levels. Reimbursement for outpatient use is specified in the HCFA Rule on outpatient prospective payment, but I don't think that that one really addresses that particular recommendation. We need a better answer on that one.

Four. HCFA should remove financial barriers to testing individuals identified by current government standards at being at risk. March '99 HCFA issued Program Memorandum 804 which clarified its coverage policy on HCV testing.

Five. The Secretary should take all necessary steps to ensure completion of current lookback programs within current recommended time frames, and the agency, FDA Commissioner Henney in March 2000, reaffirmed the commitment to enforce this issue. The Advisory Committee on Blood Safety supported recommendations 1A and 3 of the Senate's report to the House Committee on Government Reform and Oversight, and this was noted by the Department.

The current targeted lookback program should be expanded to include recipients of blood from donors subsequently identified as repeat reactive by a single EIA screening test that was licensed in 1990. This recommendation was noted by the Department. Implementation of that particular motion should be deferred until the Public Health Service had an opportunity to review and to present options for its implementation evaluation of the Advisory Committee at its next meeting.

Probably ought to have some more follow up on what the status of the lookback is, and maybe we could get that from, some statement from ABC on the status of the HCV lookback that we can put in here.

7DR. BIANCO: Mark, Celso Bianco. It's not entirely consistent with the previous, earlier, that says that there were guidances that were issued and all that. So they should match in a certain way, the two meetings on HCV.

DR. BRECHER: Well, it gets worse, because we talk about it again in the next meeting.

DR. BIANCO: I know.

DR. BRECHER: And maybe we should just refer all these hepatitis C recommendations to one summary statement. This is what actually happened.

DR. BIANCO: Actually at the bottom of each one of the issues that was read, maybe you could have a short paragraph, kind of the current status of each one of these issues.

DR. BRECHER: Yes. Because many of these issues, as you can see, they come up from meeting to meeting, and it may be simpler to just say in the end, this is what actually happened.

So again, in '99, January, the Advisory Committee recommended targeted lookback on repeat EIAs with some more specific parameters, and in June '97 there was a guidance industry from the FDA that talked about many of these areas.

Two. The Advisory believed that in light of the scope of hepatitis C, lookback current funding was inadequate for notification, testing, counseling, education and therapy. They urged the Secretary to immediately take measures to increase funding. Discussion over reimbursement issues continue.

We see that a lot when we ask people to cough up money for programs. There are discussions, but there's usually not a whole lot of action. That's a Chairman editorial comment.

[Laughter.]

DR. BRECHER: But there was a conference entitled: Identifying and Managing Transfused Patients for Hepatitis C in the 21st Century, which was held in Washington in February 2000.

Three. The Advisory Committee urges the Secretary to consider providing appropriate support and resources for blood centers and hospitals, both public and private to conduct the lookback activities, and again, similar response. Discussion continues.

CAPTAIN McMURTRY: Let me add one thing to that. There was recently an update on the hepatitis C question about a couple of weeks ago, and one of the issues that arose in the Secretary's office was how much money did the Department provide for these activities? Clearly the answer was none. And there was some concern in the Secretary's office that this had--that--the word they used was "edict"--had gone out with no support from the Department. So I don't know what that means in the long term, but at least the Department is aware that this went out, was a burden on blood collection agencies, and that we did nothing to support it financially.

DR. BRECHER: I'm sure the blood collection community is grateful that at least the issue's been raised again, and there is some regret that there wasn't some funding.

That takes us to April 1999. This must have been a short meeting because there was only one resolution here. The Advisory Committee recommended that blood products obtained from persons with hemochromatosis carry no increased risk, and basically it concluded that the Advisory Committee recognized the need for--to incentive for donation due to financial consideration. For this reason, HHS should create policies that illuminate incentives to seek donation for purpose of phlebotomy. Thus undue incentives are removed. The Department should create policies that eliminate barriers to using this resource.

In August '99, the FDA Commissioner wrote the Surgeon General to describe actions to implement this recommendation. A guidance for industry was prepared. And I think it's fair to say that this is still in flux in this country. Some blood centers are collecting hemochromatosis donors and some continue to not.

DR. HOOTS: Keith Hoots. But there is the exemption that was implemented after this recommendation, wasn't there? I mean--yes, Jay?

DR. EPSTEIN: FDA took the position that it would approve variances to waive the requirement that the medical condition of the donor be labeled on the unit, and to waive the restriction for collection only once every eight weeks. In cases where the donor had a documented hemochromatosis and where there were no fees attached to the phlebotomy.

DR. BRECHER: Similarly, the American Association of Blood Banks and their Standards Committee reworded their standards to allow for these types of donations.

DR. EPSTEIN: The part that's in flux is that it would require rule-making to remove the need to request variances, and the FDA is well aware of that.

DR. BRECHER: Thank you, Jay.

August '99 Advisory Committee concurred with the guidelines put forth on variant CJD. Donor exclusion, it was noted by the Department, the Committee requested that it be advised at each meeting about the status of the British donor deferral policy and its impact. This is noted by the Department. I think it's fair to say that sporadically we've re-reviewed this issue at this Committee.

The Advisory Committee recommended the Secretary of Health and Human Services exercise her existing statutory authority to exclude plasma-based therapies, their biotechnology analogs, and blood therapeutic alternatives from the definition of covered OPT services under Medicare hospital outpatient department prospective payment system. The Committee further recommended that the Medicare program separately reimbursed for these therapies when furnished in a hospital outpatient department including emergency rooms on a reasonable basis. And again, discussion over reimbursement issues continue at many levels, and some of this was covered in the HCFA final rule on hospital outpatient prospective payment.

The Advisory Committee recommended that the Secretary use her existing authority to exclude therapies under APC 369 from the prospective payment program for hospital outpatient services and reimburse them on a reasonable basis. This one was received by the Department.

The Advisory Committee recommends that the Secretary direct the FDA to construct the HCV lookback in accordance with prior recommendations by the Committee. November '99, FDA guidance HCV lookback was a response to this.

The Advisory Committee recommends that the Secretary work with Congress to seek additional resources to support the introduction maintenance of mandated blood safety measures, and this was received by the Department. And the Advisory Committee continued to be concerned about shortages of intravenous immunoglobulin and alpha1-antitrypsin despite laudable efforts on the part of industry and government, and the Committee supported new as well as continuing efforts to alleviate the shortages. And the Department continues to monitor the situation.

January 2000, the Committee directed the staff to create on the Committee's website a list of key recommendations that the Committee has made in a format that would permit the public to see what progress has been made on implementing each of these recommendations.

While they were somewhat on the website, I can't say that they were easily accessible on the website, and we are now attempting to bring this particular recommendation to closure, and that's what this effort is.

Two, the experience of aviation and other industries support the use in all blood establishments; i.e., blood and plasma collection centers and facilities to provide transfusion services of a confidential, nonpunitive system for the management of error and accidents not subject to regulatory requirements.

The FDA has examined its current guidance to determine if additional recommendations were needed to address investigational reporting of errors, and we'll talk about this as it pertains to some of the recommendations below as well.

All blood establishments should have a quality assurance program, and there is an FDA final rule on this issue. Quality assurance programs in all blood establishments should capture, analyze and respond to data and all deviations from established procedures, as well as errors and accidents, independent of whether the affected units were distributed or caused adverse medical events. This is thought or understood to be a component of a good manufacturing practice.

FDA should extend its current error and accident reporting requirements to apply to all blood establishments, including hospital transfusion services, rather than just licensed establishments, and this was included in the final rule that we've already talked about.

In order to facilitate improved transfusion safety for errors and accidents not subject to regulatory requirements, there should be established outside of the regulatory framework an effective, confidential nonpunitive system for the accumulation, analysis, and dissemination of data from all blood establishment quality assurance programs. This was referred back to the Committee for further consideration.

Industry and government should be encouraged to facilitate the evaluation and implementation of devices that promise to prevent misidentification of blood products and/or patients. FDA is evaluating its application process for product and recipient identification devices to ensure efficient handling of these applications. This is I think a problem that the industry continues to struggle with, as does the pharmacy industry.

April 2000. Advisory Committee recommended establishment and implementation of a national reporting and analysis system for transfusion medicine as a basis for action to reduce and prevent morbidity and mortality due to human and system error. The Advisory Committee was impressed with the accomplishments of the error reporting correction systems that have been developed to improve air travel by the aviation industry and the federal regulatory agencies within the system. This particular recommendation or acknowledgement was received by the Department.

The Advisory Committee acknowledged the efforts of the FDA, working with the blood and plasma collection industries in reducing errors and accidents and is favorably impressed with the results to date of the MERS-TM Error Management System. While a great deal has been accomplished, the Committee now believes that the opportunity exists to apply these principles to transfusion medicine.

Error Management should acknowledge the right of patients to know of any risk or harm suffered as a consequence of any error or accident related to blood products. At the same time, there should be statutory protection from disclosure for voluntary report information and of quality assurance activities that are not associated with potential or actual harm, provided that the information is also not associated with reckless or intentional harmful acts.

These Error Management Systems should complement, and not replace, current regulatory activities, notably, but not exclusively, in the area of product safety.

All analysis of collected data should be made available in a timely manner to regulatory agencies, national transfusion medicine surveillance programs and other participants in the reporting system. Again, received by the Department.

It was asked that Congress appropriate sufficient funds to develop these systems for an infrastructure, to support and maintain them in the fiscal year 2001, that Congress should stipulate that these funds should not be reallocated for other purposes and that no other funding should be reduced because of the availability of these funds. That's sort of wishful thinking, wasn't it?

[Laughter.]

DR. BRECHER: Funds necessary to maintain these systems should be appropriated annually. This was received by the Department.

Two, there was a small, but non-zero risk associated with the use of blood products or plasma derivatives that cannot be eliminated with current technologies.

The Advisory Committee, therefore, supported the prior recommendation of the IOM, and of others, that a national system to compensate a prospective national system for recipients of injuries or death caused by blood products or plasma derivatives not associated with a reckless or intentionally harmful act should be enacted and funded by Congress.

The Department continues to feel that compensation issues are the responsibility of Congress. However, it stands ready to assist Congress as it considers such recommendations in the future.

The Advisory Committee is dedicated to ensuring patient access to safe blood products and services. And whereas the Committee recognizes that fair, accurate, and timely reimbursement, including Medicare for blood-related therapies is critical to ensuring patient access to the safest possible blood--boy, someone liked a lot of commas in this sentence--the Advisory Committee, consistent with its prior recommendations, recommends that the Secretary and Congress support legislation to ensure fair and accurate reimbursement, through inpatient blood-related products and services.

Such legislation should provide sufficient funding to account for increased blood-related products, including those associated with new blood safety measures and require that these costs be reflected in annual updates of inpatient diagnosis-related groups.

The Department's reaction to this recommendation was favorable. However, the current view is that a comparable policy on reimbursement for inpatient blood and blood products use would require some type of congressional action, which has not been forthcoming.

The Committee recommended that HCFA promptly distribute guidelines for coding and billing of blood and plasma products to all entities covered by the outpatient prospective payment rule. Furthermore, the Committee urged HCFA to work with stakeholders, including consumers, outpatient departments and manufacturers to capture actual utilization and billing data, to be used to establish a permanent payment system for blood derivatives administered in outpatient settings. HCFA stated that it would do so.

Five, the Committee recognized the significant economic issues currently affecting the blood system, and the Committee seeks to review the role of various considerations and decisionmaking related to new and existing blood safety measures. The Committee was to meet in August 2000 to consider that issue.

So we go to August 2000, and our recommendations in August.

CAPTAIN McMURTRY: Well, I'm going to have to ask the Committee's help with this one. It was not clear to me that there were actual recommendations made. I read the transcripts, couldn't find an actual recommendation. Clearly, without a recommendation, I don't know what sort of follow-up there were. It was a time of flux in our office then, and I don't have a record of what happened in August of 2000. It's not in the file. So if anybody knows, please let me know.

DR. BRECHER: This brought us to January 2001, where universal leukoreduction was reviewed, and it was recommended that this be implemented as soon as possible. The Department has taken no action on this recommendation. So what are the current estimates for the percent of leukoreduction in this country?

MR. BIANCO: For platelets, it's pretty close to or--

DR. BRECHER: Apheresis platelets.

MR. BIANCO: Apheresis platelets, it's pretty close to 100 percent.

For random donor platelets from old blood, it's hard to have a figure because this is done at the hospital lab in general. But for red blood cells, I don't know somebody from the Red Cross here, but the Red Cross I believe has close to 100-percent leukoreduction of red blood cells. Among the ABC centers, about 60 percent of the red blood cells that are distributed are leukoreduced. So you could average for the country, it's about 80 percent of the red cells distributed.

DR. BRECHER: That's helpful. We can at least put that in as, in effect, what has happened. Of course, for platelet dosing, apheresis platelets I think make up 60 percent of doses currently.

MR. BIANCO: I would assume so.

DR. BRECHER: Yes. In regard to leukoreduction, the Advisory Committee is concerned about the availability of blood and the resources necessary to implement universal leukoreduction. For these reasons, the Advisory Committee recommended that the actions of the Department of Health and Human Services should strive to minimize the impact on supply, assure adequate funding for this effort, issue a regulation to implement universal leukoreduction to address these concerns and report to the Advisory Committee on a regular basis. No action was taken on this recommendation.

The Committee recommended the Secretary appoint a representative to HCFA as a nonvoting government representative to the Advisory Committee. As we'll hear later, the new charter that was signed in October 2002 does call for a member from CMS.

Given the unresolved scientific issues in the field, the Advisory Committee supports continued research in the effectiveness of universal leukoreduction. No action by the Department.

In the above resolutions, the word "leukoreduction" was intended to mean prestorage, and the resolution is referred to nonleukocyte cellular blood components.

April 2001. The Advisory Committee recognized the importance of international issues of blood safety and availability and the importance to public health in the U.S. The Advisory Committee endorsed the present activities of government agencies in this area and supports the enhancement of these activities. Specifically, the Committee encouraged the HHS to foster research, training and standard-setting activities in international blood safety, including development and transfer of appropriate technologies for the developing world. The Department has not taken any specific action on this recommendation.

The Advisory Committee supports the establishment of a mechanism to identify priorities and coordinate the exchange of information and activities among government and appropriate nongovernment agencies in the U.S. This effort should include appropriate linkages of international organizations and ongoing monitoring of these issues. Again, no specific action by the Department.

Whereas, patient access to a safe and available blood supply is a public health priority, the Committee recommended that the Secretary and Congress, A, ensure appropriate office within the Department has the responsibility to facilitate gathering and disseminating of national blood collection and distribution utilization data, analysis and development of analytical models to predict shortages.

Moreover, adequate federal dollars should be provided to support collection, analysis and distribution of these critical public health data. Specifically, the following actions should be addressed:

One, assign responsibility;

Two, support programs to develop data, assure data is collected and available to the public;

Three, encourage collaboration of blood collection centers for the purpose of identifying and addressing areas of short supply; and,

Four, encourage collaboration of plasma manufacturers for the purpose of identifying and addressing areas of short supply.

This area is being addressed. Actually, a lot of effort from the Office of the Advisory Committee has gone into this within the last two years.

Do you want to say anything more about that, Mac?

CAPTAIN McMURTRY: No.

DR. BRECHER: Okay. Thanks.

[Laughter.]

DR. BRECHER: B, support a program of public and physician education designed to improve blood and blood product donation and utilization throughout the U.S. and encourage support for such programs through the HHS.

The Department hasn't taken any specific action, but you'll see when we come back to it, the HHS has started to take a leadership role in advocating blood donation.

January 2002, a year ago. We mainly addressed emergency responses by the blood banking industry. Basically, we endorsed the AABB Interorganizational Task Force on Domestic Disasters and Acts of Terrorism as the coordinating center for the national response of the blood community. All of the other recommendations basically revolve around that, including some changes to the federal response plan.

Although this was received, it has moved forward.

CAPTAIN McMURTRY: It has moved forward, particularly in regard to Recommendation Bank there, that the responsibility under EFS 8 move to the AABB Interorganizational Task Force. The Department, while it was my understanding when I researched this that it was not complete, the Department was moving in that direction, and they would accomplish that.

DR. BRECHER: That was a quick set of resolutions to go through. It's easy when you've been at the meeting.

September 2002. Whereas, fair payment to hospitals, and blood, and blood components, transfusion service and transfusion laboratories is essential to ensure that Medicare patients have access to the best possible care, the Advisory Committee recommended that the Secretary direct CMS to establish 2003 Medicare hospital outpatient prospective payment systems for blood and blood components, transfusion services and laboratory procedures based on current-year acquisition and actual total costs for providing such products and services, rather than hospital outpatient claims from previous years. Received by the Department.

A similar recommendation on adequate reimbursement for plasma-derived therapies and the recombinant analogues was number two. Similarly, it was received by the Department.

The Department should provide increased public awareness by the ongoing need for routine blood donation by healthy persons via, A, periodic public service announcements, visible blood donations by top officials and paid advertising campaigns, funding of demonstration projects to optimize use of education and other behavior-influencing approaches, supporting specific initiatives to encourage routine donations by young persons and minorities as part of the general message of a healthy lifestyle and community support, and, D, play a leading role in increasing participation of federal employees in donating blood.

And the Department did develop a program entitled, "Give Thanks, Give Life, Give Twice," and is scheduled to be implemented or was implemented--Mac?

CAPTAIN McMURTRY: It was implemented, and there was a subsequent part of the program where the Secretary wanted the Department to step up to the line and donate as much blood as possible.

Then, the Secretary--I have to say to you I was curious whether it was going to happen, but, in fact, it has because I've gotten calls from other Departments. He has subsequently challenged the other Department Secretaries to meet the level of donation within the Department of Health and Human Services. That has actually started, and it's his plan, I understand later on in the year, to challenge industry leaders then to match the donation level of the government. So this is an ongoing plan.

DR. BRECHER: Very good. Thank you, Mac. I think we accomplished something there.

DHHS should maintain or increase funded support for blood supply monitoring, and this issue is currently being addressed within the Department.

Five, DHHS should support activities to improve management of blood inventories, defining the role of liquid or frozen reserves, integration of supply forecasting strategies directed to correct imbalances in supply need and strategies to facilitate movement of blood from areas of surplus to areas of shortage, and this was receive by the Department. I know the Department is looking at this.

CAPTAIN McMURTRY: That's correct.

DR. BRECHER: I hope this wasn't too painful. I think this is an important charge of this Committee that we get this grid as complete as possible and out on the website so that it is available to the public. I think, overall, when you look back, while some of the recommendations little or no action was taken, I think, on balance, this Committee has done pretty well would be my assessment.

Keith?

DR. HOOTS: It struck me, after listening to Paul's historical review of where we've been, and then going through these in order, that, clearly, not surprisingly, resource allocation quickly jumps to the top of the impediment to what we would like to see happen.

I don't have any obviously great solutions to this. It seems like that since, at least in the initiation of this Advisory Committee, Congress did have some sort of imprimatur for its creation that perhaps, at least at some point, we might discuss how, obviously, we advise the Secretary of Health, and that's clearly what our mandate is, but we might want to at least talk about strategies to see how the information about these recommendations get disseminated more widely to perhaps help the Secretary because, obviously, he has not unlimited resources, and obviously they're contracting. But if he has to go and prioritize within existing resources, without at least some exigency from outside, it may be very difficult for some of these things to ever happen.

But if other members of the government, outside of the Secretary's HHS Office, were aware of the importance, perhaps, maybe it would--I don't know. I don't have any great strategy to do this, but it just seems like that's the recurrent theme.

DR. BRECHER: That may be something we might discuss when Dr. Slater comes a bit later.

Ed?

DR. GOMPERTS: Ed Gomperts.

Just looking through this substantial body of recommendations and responses, the Committee has been going for about five-and-a-half years, and it's appropriate that the Committee lookback at its original charge and also what has been accomplished.

Very superficially, as you went through this and reconsidered a number of points here, broadly speaking, there are links over the years between one Committee deliberation, recommendations, et cetera, and quite often there's follow-up in subsequent Committee and subsequent recommendations.

Of course, we've dealt with supply, and we've also dealt with the availability issue again and again looking at different topics. It would be useful, certainly from my point of view, to look back over the years and follow through the links. Some of the issues clearly have been dealt with and closed. The HCV lookback is obvious.

The new variant CJD issue was dealt with, but, to some extent, quiescent, but might become an issue in the future. Just where do we stand with that?

The availability issues, again, we looked at certainly the plasma derivatives, and by and large what is the status today? And, of course, the reimbursement issue, where does that stand.

So it may well be that some topics that were addressed three years ago could well still be very pertinent, and it may be an idea to relook at them from the point of view of status.

So, as we go through this and identify the particular recommendation, the response, current status, it's probably a good idea, also, to bring it back to the Committee to deliberate as to the need for relooking at these things with potentially subsequent recommendations.

DR. BRECHER: We actually have formed an Agenda Subcommittee to try to plan for the future for meetings, and, tentatively, for the next meeting we were talking about discussing national blood policy. Whereas, reimbursement would be a major component of that, and so I think that that's right.

We probably need to bring to closure those early meetings on hepatitis C lookback and probably ought to have a summary of what actually happened, and I think we can certainly do that as part of the next meeting as well.

DR. GOMPERTS: Yes, there's a substantially history that's been established, and it's good to look back and to start tying things together.

DR. DAVEY: Mark?

DR. BRECHER: Yes, Rick?

DR. DAVEY: Rick Davey.

First, I want to commend Mac and the staff. This has been a very useful, interesting historical perspective. I don't know what grade to give the Committee on how we've done, maybe a B, but we've certainly accomplished some good stuff.

DR. BRECHER: Is that a B for blood?

[Laughter.]

DR. DAVEY: B for blood.

Obviously, there are other Advisory Committees, BPAC and TSEAC, that have addressed similar issues. And it might be useful, in pulling together this summary, to occasionally, when appropriate, cross-reference what has been addressed and recommended by these other Advisory Committees because there's often considerable overlap in what the committees address, and occasionally the recommendations may not be entirely consistent or, on other occasions, they may be very complementary.

But I think it would be useful for this Committee, as kind of the oversight committee, if you will, the Advisory Committee to the Secretary, that we have a full understanding, where appropriate, of what the other two key Advisory Committees that have addressed these issues, where they've stood on these particular issues.

DR. BRECHER: Mark, I'd like to echo Rick's comment. I think this is a great work product.

Just a couple of things for consideration. I wonder if it would be useful to take each of these recommendations and try and link them back to the charter just to show that there's some kind of alignment between what the Committee is actually doing and what it was chartered to do just to kind of close the loop there.

As another question, I was wondering if you have a date in mind, if you're giving us an assignment, you want comments back by a certain date in order to try and facilitate this process along so we'll have a final document to look at next time.

DR. BRECHER: Yes, your homework, Committee members, and there is a huge amount of expertise and experience on this Committee, is to please look at this very carefully. Let's make this as accurate a document as we possibly can.

I would ask that you get all comments back to Mac within a month, let's say by March 1st. We'll then integrate all of those comments and distribute them. I'd like to have the next draft available by the next meeting, and at that time, we'll get it to you before the meeting. I apologize that this came late.

Mary?

DR. CHAMBERLAND: Mary Chamberland.

One thing I think that we're going to have to do, and I agree with taking a careful look at this and getting comments back by March 1st, one thing that we're going to have to try and struggle with is this balancing act between the document as it's structured now I think is to, with the intent of sort of at a glance to be able to tell you what the recommendation was and what the action was.

I have some concern that for several of these recommendations, the appearance in the result column of no action is really an inaccurate representation of what's happening within the PHS. For example, the first recommendation for April 29, 2001, had to do with international blood safety-related activities and encouraging the Department to foster research, training, standard setting, et cetera, and the response is Department has taken no action.

Clearly, agencies like CDC, the NIH have very extensive programs that relate to international blood safety and support for these et cetera. So I don't think what we want to have is this document then become some sort of summation of the PHS activities in these pertinent areas, but by the same token, it's not accurate to say that there's no action. So I think we might have to struggle a little bit about these responses.

There were similar things that had to do with surveillance systems for CJD, for emerging infectious disease agents, et cetera. A lot of those have been developed. Actually, some of them are quite mature now, speaking for some that come out of the CDC. So I think maybe we might want to have a little bit of guidance as to how we want to approach this because this could then become some voluminous document, and I don't think that's the intent here.

But by the same token, I think it's misleading to give the impression that not a lot has been done, when in point of fact, a lot of the PHS agencies, sort of in parallel with the Committee, have been working in these ares to develop and implement a number of activities.

DR. BRECHER: I think that's a very good comment, Mary. I agree with you completely. I think we strive to be succinct, and we can link out to many of those other sites, if the Committee members could provide us the pertinent links. That way I think we can be short, but still informative.

Jay?

DR. EPSTEIN: I want to come back to the point that Ed Gomperts was making, that many of the issues at different meetings are, in fact, linked thematically. I'm just wondering whether it would not be more useful, as a public communication, to summarize this work thematically, rather than recommendation line-by-line.

I think, to get back comments in a month line-by-line and fix all errors makes good sense, but I think we would have a better summary if we had the theme, a summary of all recommendations that were made over time, and then a discussion of the responses that have been made, both by government and the private sector on the issue because I think that the line-by-line analysis is too simplistic.

It ignores the fact that the actions taken by government and the private sector may not be in direct response to the recommendation, but may reflect other inputs and influences, and I think that we'll get further down a path of useful communication if, instead of pretending that it's a one-to-one relationship, we have instead a description of the issue, a description of the recommendations, and a description of the events that have transpired because I think that will then somewhat mitigate against a simplistic one-to-one interpretation which would not be correct.

DR. BRECHER: Yes, I think that's a very interesting alternative approach. We could have thematic approaches for HCV lookback, errors, blood supply, reimbursement.

We're here to do the Committee's bidding. And so I guess what I would ask the Committee, what is it that the Committee would like us to do?

MR. BIANCO: Yes, I want to support--Celso Bianco--very much what Jay said.

You have the impression, because a lot of the sentences, recommendation was received by the Department or things like that, they give a misimpression that the field did not evolve, and we had a tremendous change in the last five years in many of those areas.

I think that the Committee was, even if I wasn't here, the Committee was instrumental in bringing and raising the awareness, so I missed the opportunity to be part of it, but I watched it, and that was very, very important and I want it to be recognized.

DR. KUHN: Dana Kuhn. I think if the intent of us as a Committee is to review all of this information and to put it on a website where the public can see it and see what kind of progress we have made over the years, it's going to have to be simplistic enough for a citizen to be able to read and understand exactly what's happened.

But I do concur with the Committee that we should have it in a sense of being thematic, seeing what recommendations, and I think there has to be a little bit more detail, like the past recommendations we just had at the last meeting. When I read the letter that Dr. Slater wrote to Mark, there was some very strong comments made in there like, "I will recommend. I will contact," the CMS and so on and so forth, where in this document it just says, "received," the recommendation was received.

So I think there has to be more clarification on a little bit more of what happened because if people read it was received, that might connote that nothing was done, but there has been something done.

DR. BRECHER: So what is the sense of the Committee?

Mike?

COLONEL FITZPATRICK: I think if we relate back to what Paul brought about as the historical perspective, what we have here is more of a table to follow, like the minutes of Committee meetings, what's open, what hasn't been accomplished, what has been. But to communicate the accomplishments or the structure of the committee, what's been happening to the public, we have the IOM study that created the Committee, we have a charter which are both relatively thematic, and then we have resolutions that have recurring themes.

So I think the thematic idea is essential, and as Dr. Goodman said, there's really two constraints; one is resource allocation, the other overall constraint is supply. Every recommendation, every new deferral, everything that has been considered by either BPAC or this Committee has been constrained by its impact on supply or perceived impact on supply.

And if we go back to the IOM study as to why the industry and the government dealt with HIV the way it did, a lot of that was perceived impact on supply. And so I think if we have broad, general themes and indicate the progress of the Committee to impact that relating back to the IOM study, we'd be able to show to the public the progress that has been made to not prevent errors because it's easy in hindsight to say there were errors, but how to change the way we deal with risks to the health of the public through blood transfusion.

I think, thematically, you may want to portray it that way, but you may want, for purposes of clarity to the Committee as to where they're going, provide them something like this table so that you have an idea from meeting to meeting what's following through, and then you have a broad, general overview thematically of the progress of the Committee since the IOM study.

DR. BRECHER: Dr. Penner?

DR. PENNER: As I see it, the weakness of the document relates to its failure to provide the responses and that it hasn't been developed, and the follow-up has not been present for a number of these items that we've considered over the years, particularly the first item that we covered, which was the hepatitis C lookback. Despite the fact that it was reexamined on a number and revisited on a number of occasions, we have no idea of any significant accomplishments in that area because we have not had any update to see what has occurred.

DR. BRECHER: Let's take a vote of the Committee. I think the basic question before is, well, I think we all agree that there has to be some report card of what's happened, and then we can either do it, basically, as line items, as outlined here, or in broad, thematic strokes.

So all those who would prefer that we reconfigure this in a thematic approach, please raise your hands.

DR. LINDEN: Can you tell me who is the target audience for this.

DR. BRECHER: The public. I think this is to educate the public about what the Committee has accomplished.

DR. KUHN: Are you talking about thematic, with what the Colonel just said about linking it back to the charter?

DR. BRECHER: I was thinking more in terms of the major themes that have run through these meetings, such as supply, errors, HCV lookback, those kind of themes.

MR. WALSH: Mr. Chairman--Walsh--I agree with the thematic approach. I think that would be the most constructive and understandable for the general public, but I think it would also be beneficial to complete this analysis in the sense of making it more accurate and more complete on a line-item basis, and then utilize that as a background for the thematic presentation.

DR. BRECHER: Sort of do both.

MR. WALSH: Yes.

DR. BRECHER: So we now have three choices: line item, themes or do both.

All of those in favor of doing both, please raise your hands high.

[Show of hands.]

DR. BRECHER: I think that's clearly the majority. We will do both.

We're running a little ahead of schedule, but why don't we take our break now, and we'll reconvene at 10:30.

[Recess.]

DR. BRECHER: If everyone could take their seats, we will reconvene. We're going to restart.

Our first speaker in this second part of the morning is Jon Moreno, University of Virginia, talking about ethical considerations of medical decisions.

Jon?

DR. MORENO: Thank you. I want to thank the members of the Advisory Committee for giving me the opportunity to talk to you this morning.

When Mac called me a couple of weeks ago to ask me if I would do this, my first reaction was that I really had nothing to say about this that wasn't painfully obvious and that I ought to decline. In a few minutes, you may well decide that my first intuition was the correct one.

Nonetheless, since I paid to rush in where supernatural creatures fear to tread, the more I thought about the subject matter, the more interested I became and the more complicated, it seemed to me, it was.

I want to say that the way that this topic was framed by Mac, and I suppose by others as well, was, well, really, in the face of a matter of grave public concern, partly media driven, to which, therefore, elected officials feel the need to weigh in, taking, as an example, the West Nile Virus experience, how in the face of that kind of pressure and the need to satisfy public concern, how can people in authority, who are supposed to be experts and professionals, how can they continue to exercise their expertise and continue to focus on ongoing chronic, continuing public health problems, while at the same time being responsive to public concerns.

So one of my first reactions was, damnit, they ought to just get some backbone and do it, and they don't really need anybody like me to come in and tell them to do it, but then I started talking to people about this, and they said, "Well, I think somebody like you ought to come in who is disinterested and unburdened by a lot of knowledge about blood and the way the system works," and so I've decided to do this rather eclectic presentation that I put together the last couple of weeks, and really perhaps it ought to be called ethical, and philosophical and historical considerations as much as ethical considerations.

But this is sort of roughly the way I'm going to approach the issue:

First, by putting some facts on the table that come from several of you, actually, in your publications--facts that are as well known, better known to you, certainly, than they are to me; and then talk a little bit about what I call creeping precautionism as a reaction to some of these recent concerns; and conclude with a little disquisition on what I call the burdens of expertise, involving the notion of fiduciary knowledge. That's the trust that resides in you, as experts, that people like me reside in you to protect me from things I don't understand and to keep a balanced view of matters, the virtue of equanimity; and then a little reminder from Philosophy 101 about where the idea of expertise comes from in the Western tradition, and I'm actually going to conclude by making some historical remarks about the role of scientific advisory committees in a democracy.

First, just some facts that I've gathered from Mark, as well as others, with respect to the ongoing continuing problem of bacterial contamination in the blood supply. This is not data that you're unfamiliar with, of course. I was struck by the observation that perhaps one patient a day develops a life-threatening infection due to bacterial contamination, and that it's vastly more likely to transmit infection than HIV, hepatitis C or West Nile and that some of the sickest people in our hospitals are the most likely to be recipients of these units.

There seems to be consensus in your community that contamination-related transfusion reactions have been continuing in the past two decades, but the number of deaths that are reported to the FDA each year has been said by Jim MacPherson to be probably the tip of the iceberg; namely, about 10 to 15 a year, and I would actually challenge the Advisory Committee to examine the reporting problem and figure out ways of ameliorating it because it seems to me that we do need more data on the actual number of deaths from bacterial contamination than we seem to be getting.

Now, I know that there's going to be disagreement around this table about whether these are examples of what I'm going to be calling in a minute "creeping precautionism" in blood services, and I accept that there is going to be disagreement. Yet, a number of people I've spoken to in the blood world and in public health, more generally, have spontaneously given me these examples when I've asked for them.

I've asked colleagues in different parts of the country, in different fields, what are some examples in which we might have actually gone too far in recent years and been too cautious, been to risk averse, in other words. And the examples that come up, in fact, have already been mentioned this morning, interestingly; the deferral of people who lived in Europe for CJD, and p24 antigen testing for HIV.

Again, I'm not here to assert that these are examples of excessive risk aversion or what I call creeping precautionism, but let's suppose that they are, just for the sake of argument. Humor a visitor.

I think part of what's going on here might be that the original precautionary principle articulated by Europeans in the last 10 years or so has been taken, to some extent, out of context. Here is a sample statement from the European Environment Agency that articulates the precautionary principle, a principle adopted by the U.N. Conference on Environment and Development:

"That in order to protect an environment, a precautionary approach should be widely applied; meaning that where there are threats of serious or irreversible damage to the environment, lack of full scientific certainty should not be used as a reason for postponing cost-effective measures to prevent environmental degradation."

Now, that's a double negative, but you get the point.

Secondly, that the precautionary principle permits a lower level of proof of harm to be used in policymaking whenever the consequences of waiting for higher levels of proof may be very costly and/or irreversible, and I've emphasized the phrase "very costly and/or irreversible," just to show you that again because I want to come back to that. Because I think that the way we interpret this notion of cost and irreversibility is critical with respect to blood services.

Here is another statement, a more recent statement about the Commission that I want to also refer to in a moment, again. This communication that they're talking about makes it clear that the precautionary principle is neither a politicization of science--or at least it should not be a politicization of science--or the acceptance of zero risk, but that it provides a basis for action when science is unable to give a clear answer; namely, preventive action.

Now, I think that the precautionary principle has become, in recent years, a basis of support for a very risk-averse attitude in areas other than the one for which it was originally intended; namely, environmental protection. I think that this has happened partly because the original context of the principle has been torn away in some recent conversations.

Removing the concept or the principle of precautionism from the environmental or ecological context and applying it directly to the public context requires more analysis I think than it's been given. In particular, to take the notion that the possible harms might be very costly and/or irreversible, to take that notion and to imply that even one death is unacceptable is a respectable view, but it's a view that requires defense, and I don't know that it has been adequately defended.

The original notion, again, was that the notion of high cost and irreversibility should be applied to profound climatic change. If we now take that notion and move it into a different area, then I think that transportation of the principle requires more defense than it's gotten among people like us in the last few years. That's not to say that it can't be defended, but I don't think it has been.

Now, of course, precautionism, particularly in the context of blood services, and I actually gave a talk once to the AABB in which I used the term "the blood industry," and some people were offended by that language, so I'm going to say, more neutrally, blood services.

The principle of precautionism, arguably, is supported in this context in light of the HIV experience; that blood services are an especially sensitive area and public trust must be retained in order for the system to work. Obviously, I'm very sensitive to this argument.

But it doesn't follow that a zero-risk philosophy must always be adopted in order to retain public trust. In fact, one could argue that this is a two-edged sword. The other edge of the sword is that the public trust in the expertise of people like you may eventually be eroded if immediate concerns, media-driven concerns, politically-driven concerns, are permitted to eclipse the bigger picture, and that I think, arguably, is, to some extent, what has happened with respect to blood services.

Now, the people sitting around this table, and your colleagues at your institutions, universities, agencies, are burdened by being experts. I want to reflect, for a moment, with you on what it means to be an expert, what it means to have special knowledge.

It means, for one thing, to be a steward of some specialized knowledge that the rest of us don't have, either because we haven't spent all of the time learning it or because we're not equipped, by virtue of our educational background or intellect, to obtain it. The knowledge that you possess is communal, but not everybody in the community can have access to it. You are literally stewards, people like you, are literally stewards of that knowledge.

Experts have what people in ethics called a beneficence-based duty to express their educated opinion; that is to say, the knowledge that you hold on behalf of the wider community is a trust, and we expect you, I, as a nonscientist, expect people like you to express your opinion and, in some cases, be willing to take some hits if you're wrong.

For you to express your opinion is not, it seems to me, an exercise in paternalism. Paternalism is a distorted expression of authority over people. There's nothing in appropriate or distorting about people who actually have some knowledge to make a reasoned, educated judgment, and again that expertise resides in a scientific community and not in individuals

I expect that you're going to talk to your colleagues, that you're going to consult with your colleagues about the judgments that you make so that it's the entire scientific community, upon which I, as a nonscientist, rely for information and ultimately for protection.

Part of what you possess is what the philosopher, Peter Caus, one of my old professors, calls fiduciary knowledge. I trust you, as I trust my doctor in the clinical setting or a lawyer I might consult or my stockbroker, to know some things I don't know. Even though I can never know them, I have confidence in your judgment because I respect you as an expert. I trust your knowledge, I trust that you will advise me honestly.

And even when, as is often the case with our portfolio managers these days, you may turn out to be wrong, I believe that you owe me the responsibility, as someone who has invested in your skill and your expertise, you owe me the responsibility of telling me what you think is the best course of action for me.

Now, to take the hits associated with being an expert requires the possession of an old virtue that hardly anybody ever talks about any more that the old medical philosophers used to talk about, which is the virtue of equanimity. In fact, if you look at the Hippocratic writings, you see that Hippocrates talks about equanimity when the doctor goes into the patient's room, and the patient is suffering and dying, and the family is in agony, and it's so important for the doctor to retain a sense of detachment and judgment in the midst of the chaos that surrounds the doctor.

This is, in fact, a cornerstone of medical professionalism, the virtue of equanimity. I don't expect my doctor to get upset when he reads my chart in front of me. If my doctor starts to get upset, and looks panicky and tears come to his eyes, that doesn't help me.

I expect, in fact, a kind of detachment, a friendly detachment, but a detachment nonetheless. Sir William Osler put this well more than 100 years ago, and he expressed also how experts, like doctors, can take their hits from appearing to be cold and insensitive, when, in fact, they're trying to retain a measure of personal detachment. From its very nature, he wrote, this precious quality, imperturbability, he put it, is liable to be misinterpreted, and the general accusation of hardness so often brought against the profession has here its foundation.

Of course, it's only within a few years of Osler's statement that the profession of public health emerged, and I'd argue that imperturbability, the virtue of equanimity applies as well to people in public health fields as to clinical physicians.

To make this point, in a larger philosophical sense, I want to remind you of the origins of the notion of expertise in our culture. Now, those of you, again, who haven't been reading "Plato's Republic" recently, there's an image in "Plato's Republic" that's very powerful. It's part of our culture, it's part of our language. We're inured to it. We don't even remember it any more.

But it's what is supposed to separate people who really know something from people who don't. And the general image, you might recall from your philosophy course, is that of slaves, shackled in the bottom of a cave from birth. They can't move, they can't look anywhere except at the wall in front of them. There are people carrying objects behind them, in front of a light source, and the shadows of the objects are cast on the wall in front of them.

What's the result? If you ask these people, "Well, what's real in the world," they would say, "Well, these things I see in front of me." In fact, of course, those things that they see in front of them are only shadows.

Well, one day, according to the story, one of these slaves gets free, climbs up to the top of the cave and sees that there's a whole world out there and that, as a matter of fact, what he thought was a real thing was only a shadow, but that there are real objects that are more real than the shadows, that the sun gives light, and therefore that the sun is the source of the good, the source of truth.

He is illuminated. He is illuminated, and he knows now that what he thought was real was not. He's become an expert, and he's become an expert because he's been illuminated by the light of truth. This is the original notion of expertise in Western society.

And when Socrates' students say these are very strange people indeed, this is a very strange situation indeed, Socrates shocks them, the climatic line is, "They are like us." All we see is the shadows.

Now, expertise, particularly scientific expertise, gives people like you the opportunity to see beyond the shadows in a way that I never will. So can we, in a democracy, function with experts? Plato didn't think so. Plato, as a matter of fact, as you might recall, regarded democracy, in its literal Greek meaning, as the rule of the mob, partly because the mob killed Socrates or at least found him guilty of making the lesser the better cause and corrupting the youth of Athens.

Plato did not think, and by the way Aristotle didn't either, the first real observational scientist, that expertise, that people who knew the truth could really function in a democratic context.

And so what your job is, and not to make this too grandiose, but I think it's nonetheless true, the job of scientific advisers in a democracy is to prove that Plato was wrong and that your expertise, while it must bend to public concern, must not break.

And in fact this is a fairly recent experiment; the idea of systematic, scientific advice being given to government. That idea is only about 100 years old. Teddy Roosevelt appointed the first Presidential Advisory Committee, the Country Life Commission, about 100 years ago. It's only since about the 1930s, and since the Roosevelt administration, the second Roosevelt administration, that experts really had a systematic role in policy development, and this is an ongoing experiment, and there's no guarantee that it will succeed.

If it succeeds, it will be because people like you have decided to resist the pressures of the moment and continue to give your best wisdom knowing that you might turn out to be wrong.

So I'll end with Dr. Osler, again, on the equanimity of the expert: "A rare and precious gift is the art of detachment, by which a man..." and presumably a woman "...may so separate himself from a life-long environment..." something like the slaves in Plato's cave, right? "...as to take a panoramic view of the conditions under which he has lived and moved. It frees him from Plato's den long enough to see the realities as they are, the shadows as they appear."

So your job, speaking again as a citizen and as a nonscientist, is to help me look beyond the shadows and to help me to be illuminated.

Thank you very much, Mark. Thank you, Mr. Chairman.

[Applause.]

DR. MORENO: I don't know that there's any questions that could possibly be asked of me, but I'll hang around here in case there are.

[Laughter.]

DR. BRECHER: Thank you, Jon. It was very illuminating.

[Laughter.]

DR. MORENO: Well said.

DR. BRECHER: And I didn't put him on my bacterial stuff.

[Laughter.]

DR. BRECHER: Paul?

DR. McCURDY: One of the things that was recognized, I think, in the IOM report that I summarized earlier was that patients were not taken into consideration and were not included in the equation when decisions were made in the '80s, as to what to do.

At that time, I was a blood center director. I brought together the physicians taking care of hemophilia in the Washington area, asked them if they were interested in shifting to cryoprecipitate as the treatment, rather than concentrate, and they said, no, they did not want to do that. I was prepared to make enough, so they could, but they said, no. They made this decision on behalf of patients, and the whole patient-physician relationship is still evolving from the point where the physician sits up here, and the patient sits down here, and the doctor orders.

Whereas, it's now getting closer to where the doctor discusses and discusses the alternatives and the risks, and I think that's very important to include in that area, in the equation, that this may be a group of experts, but there was a similar group of experts or several groups of experts in 1992/1994 that made decisions on behalf of patients and were seriously criticized. They did their best, they took their shot, and they got shot.

MR. MORENO: I mean, I think you're--what Dr. McCurdy said is quite accurate, and we're still trying to figure out how to address this balance.

My field, bioethics, of course, got started because of, in large measure, concerns about physician paternalism. And nothing I've said, I hope, suggests that we ought to return to the bad old days. Nonetheless, it doesn't seem to me to be paternalistic for people in a position to know more than I know to give a strong recommendation. And to remove it now from the clinical setting to the policy setting, it seems to me even more important that the scientific community, speaking through you, speak with a clear voice about what's best for me, and if I ignore it, I ignore it at my peril. But at least I can't come back to you and say you weren't straight with me and didn't give me the benefit of your best thinking.

DR. BRECHER: Jay Epstein?

DR. EPSTEIN: Well, more or less along the lines that you were just discussing, the question that we face is what lies after the so-called precautionary principle, albeit in the supply. And a lot of energy and effort has gone into trying to craft systems that will somehow come up with perhaps not better answers but better accepted answers. And I just wonder what your thinking is on the nature or characteristic of such processes. What would it look like if we did it right?

MR. MORENO: Well, that wasn't what Mark asked me to talk about.

[Laughter.]

MR. MORENO: I'm not going to pretend, Dr. Epstein, to be an authority on public health systems. My question is this, or my point, I suppose, is this: If people walk away from a meeting like this, if people finish drafting a document in an advisory group like this, and yet have the sense that they haven't been as forceful as they should be about what they think is in the best interests of the society, then I think that would be an earmark of what I've called creeping precautionism. That's the standard that I want to adopt this morning. I'm going to leave it to people who know how to design these systems to fill out the details. I'm not going to go beyond my expertise, having praised expertise in principle this morning.

DR. BRECHER: Dr. Penner?

DR. PENNER: I'll support Paul's comments and perhaps maybe take a slightly different view of the expert's role as we see it right now. That seems to me that we have the responsibility for conveying information so that the public can make educated choices. We can't make the decisions for the public. And that seems to me much different than we've had in the past in the way of approaching situations where we have information and we're not willing to divulge it and make the decision then for those individuals.

DR. BRECHER: Chris, do you want to go first?

MR. HEALEY: Thank you. Chris Healey.

A potential contradiction I see in what you've said is that if we act with equanimity and detach ourselves from our environment to some extent, to exercise expertise in the best interest of society, we almost by definition are going to incur the ire of that society or at least the suspicion of that society because we won't be viewed as being sensitive and engaged to their particular needs.

So one of the challenges--one of the contradictions I see is how do we attain that level of detachment to act appropriately, yet at the same time act within the democracy where we don't incur their ill feelings, ill will.

MR. MORENO: Well, "contradiction" is a fighting word, you know, talking to a philosopher. I think it's a tension, and I think it's an inherent tension. And if people take on the kind of role that professionals take on, then it's an illimitable tension in the role. I don't see a way around it. I think it constantly has to be negotiated.

Now, as an attorney, you undoubtedly have occasion to talk to clients to whom you give advice, and the advice turns out not to be--I'm sure you're an excellent attorney, but it might not turn out in retrospect always to be the best. You've done the best you could. And that's really all that we can ask, but I don't think that there is any easy exit. I think that's part of what it is to be an authority in a subject area which people invest some trust, reside some trust in you. And it's especially hard in a democratic context.

MR. HEALEY: So are we doing our jobs right if people aren't particularly happy with us who--

MR. MORENO: Yeah, I think sometimes you are. But I think it does have to be done with sensitivity and making every effort to reach out and explain to people what the position is. But sometimes the best medicine is--you know, this is heteropathy, not homeopathy. Sometimes it's necessary to take a position that is unpopular, and you're not elected officials so you have the luxury of doing that without worrying about the next cycle, the next election cycle.

DR. BRECHER: Larry?

MR. ALLEN: While I agree with some of the statements that you made and some of the people on the committee have made, I think that when I look at it in one respect, there's a history here that this field is not--we didn't start out with a level playing field and that for certain people makes a difference.

I think for the average person in this country going to the doctor, it's okay if you want to be a spectator in your own health care and let that doctor dictate the path for you. But in many cases, that's not the way it should work. And something you mentioned earlier about we don't expect our doctor to get emotional when he reads our chart, nor at the same time do we expect our doctors or researchers to accept our fate without compassion. And I think there has to be that balance, that understanding within the patients that the doctor--at some point the doctors have to go beyond the norm because of what these people might be dealing with.

MR. MORENO: Absolutely, and nothing I've said should be construed as an argument, again, for old-fashioned paternalism or for lack of compassion. All I've argued is that it is--that the phenomenon that I see happening among physician colleagues these days, which is worrisome, namely, that too often if a patient asks for a recommendation, a doctor will essentially hide behind the principle of autonomy, which, unfortunately, people like me have been teaching for the last 25 years, and say, "Well, I can't make a recommendation; it's your decision. I can't tell you, you're the one; it's not me." And that I think is an example of going too far.

DR. BRECHER: Rick?

DR. DAVEY: Yes, one of your comments certainly resonated with me, that we have to be careful of letting immediate concerns eclipse the bigger picture. Clearly I think in our field we've been--many of us have been concerned about reacting quickly to the problem de jure, whether it's West Nile or vCJD or any number of other issues. And yet when we perhaps want to look at this in the larger context, maybe some of us have difficulty in defining what the bigger picture is. So we're kind of left at the end of the day with a series of responses to immediate concerns without a context of a bigger picture that we can be comfortable with.

I wonder if you might come in on that at all.

MR. MORENO: I mean, I think that's one of the benefits of working in a group, you know, that you have peer support, you have the benefit of colleagues' expertise about related areas, and you have the opportunity to kick back and try to obtain a bigger picture in a social context that's so hard when you're sitting alone in your office.

So I would say that's--you know, the good thing about a committee is that you have people with whom you can reflect. And the bad thing about a committee is that it's a committee. But there are some virtues in the social process, even though they take a lot more time.

DR. LOPES: I should say by way of outset that I'm the person on this committee who's here representing the mob, or at least the mob psychology. I was interested in reading the executive summary of the IOM report that Recommendation 6 said where uncertainties or countervailing public health concerns preclude completely eliminating potential risks, the FDA should encourage and, where necessary, require the blood industry to implement partial solutions that have little risk of causing harm.

This strikes me to be a precautionary principle stated in the medical arena. We have seen on this committee experts in the blood services industry speak not only verbally but also by the actions of their groups in areas like universal leukoreduction where it wasn't--this is a partial solution to a very unclear problem, but there was a lot of thinking there, I think, if I remember correctly, that this was something that would not cause any harm and might do good in application of the precautionary principle.

I'm just wondering whether you think that a suitably phrased precautionary principle could never be relevant in medicine. I just don't see why the environment is different in principle, given that for at least some of the things that we faced, major and irreparable harm has been done in allowing, say, an epidemic like AIDS to go as far as it did.

MR. MORENO: I agree. There's no reason in principle that it couldn't. And perhaps we get into difficulties when we start to think in terms of avoiding all risk. Perhaps it's the notion that we can live in a risk-free world that begins to create trouble. But I absolutely agree with you that, in principle, it should be possible to apply such a concept.

I think that what often has happened, though, as I asserted earlier, is that it's kind of crept up on us without analysis, and that it seems to be the easy way out, that it seems to be the prudent approach, isn't always, it seems to me, the right approach.

MR. SKINNER: What I'm trying to rationalize in my mind is I come to this committee as a layman or as a consumer. I don't come from a medical or a technical background. So my expertise are life experiences and what I've learned along the way. And what I think this committee is supposed to do is to kind of balance that knowledge and power base into equilibrium. And I'm wondering if we don't come and have different roles and if the consumer's role here has a little bit different standard than what was articulated here, at least the approach which we've taken really is the approach of zero tolerance approach and until, you know, the knowledge and power and we're persuaded otherwise to accept something different than zero tolerance. How do you--do you see the roles of committee members different as opposed to what seemed to be kind of one global role that governed the work of the committee?

MR. MORENO: Well, I've been on advisory committees and I've been staff to advisory committees, and I've thought a lot about this very interesting question about the notion of representation on advisory committees, and I'd like to talk to you about that, actually, on another occasion.

But in this case, I guess I--I'm a consumer, too, and I'm a lay person, not a scientist or a physician. And I want to know what the downside is. There's always a downside. Take zero tolerance, something's going to be left out. And I guess I'd want to know what I'm letting myself in for. If I avoid one risk, what am I--what's the possibilities of others? And I would need, again, the benefit of the experts at the table to let me know, you know, what that balance is.

DR. BRECHER: Mike?

COLONEL FITZPATRICK: Just going back to the creep theory and the zero tolerance question takes me back to what I said earlier about supply. The balance this committee and others struggle with is always the impact of harm in the context of there not being enough blood available from the actions that the committee takes or the regulatory body takes on recommendations of the committee.

MR. MORENO: Right.

COLONEL FITZPATRICK: But the perceived application of the principle is to move towards zero risk, and the closer we move toward that, the less impact we make on safety, the more impact we make on availability. And the models that have been presented to predict the impact on availability for each new thing we have incurred have not been correct. When we say we're going to see a 15-percent reduction in donors, we don't see a 15-percent reduction in donors. And we don't have good, factual explanations of why that occurs, but we have observation that it does.

But we have observation now that we have a distinct problem with supply, and I guess one of the questions I have for you is: How do we as a committee measure that irreversible harm to an individual versus the group? And how do we arrive at an acceptable model of--you know, one failure in 5 million for brakes on a car is acceptable. One failure in 12 million for testing for blood appears not to be. How do we balance that?

MR. MORENO: Lots of people have talked about this, as you well know. There's no right answer. There's no algorithm. I think finally it's a political judgment. But it's a political judgment in the grander sense of politics. It's a social judgment, what people in general are comfortable with given the risks on the other side, the availability problem, if we were to know them. And I appreciate that we don't know them too well.

But, again, I think that's--in order for people like me to make a judgment like that, I need information that you can provide. But I think that there is no magic bullet that's going to give us that answer. It is a political judgment, and it may vary, irrationally, from one context, as you mentioned, to another.

DR. HOOTS: You emphasize knowledge in terms of expertise. Mark was talking about coming at it from a different perspective. Is that really what we're striving for rather than knowledge in terms of conferring expertise in bringing to the occasion, decisionmaking, some semblance of wisdom which would reflect both knowledge and experiential impact of exercising of knowledge?

MR. MORENO: Absolutely. Experience counts for a lot in the clinical setting. It counts for a lot in the public health setting and policymaking. The knowledge that a representative of the consumer can bring is the viewpoint of the consumer to make sure that's on the table all the time. That's got to be part of the mix. Absolutely. Otherwise, we're in an aristocracy rather than a democracy, but I would hope that we'd be in a scientifically informed democracy. That's the hard thing.

DR. HAAS: The broad model you sketch out is relatively familiar to me in the sense that my training as an economist gets me into the abstract world of philosophers on many occasions. A point that Larry made a little bit earlier is one I think that's really important here in the sense of trying to get the big picture, as you stated. I would suggest certainly in this area it's not the big picture, it's the big pictures. They're different in this group, the population at large or groups of individuals who have chronic blood needs.

MR. MORENO: Right.

DR. HAAS: And that, again, creates another one of the trade-offs that you're talking about.

MR. MORENO: Right. Agreed.

DR. BIANCO: Ron first.

DR. GILCHER: In a sense, this is--one could relate it to the two basic biologic drives, that is, self-preservation and species preservation. And I take that then to individual rights versus society's rights. And that's the balance that we have here and have to determine which is the right approach.

If I as an individual am going to be transfused, I want zero risk. On the other hand, we know that we can't attain zero risk. So we have this very fine balance.

MR. MORENO: Right. Moreover, of course, we're aware of the individual who's going to be transfused. We're not aware of the individual who doesn't have access to any blood because of the protective measures that have been used to make sure that individual who's going to be transfused is not at risk. So it's also important to keep in mind the statistical victim as well as the concrete recipient.

DR. GILCHER: What I might say is that statistics don't apply to a single event. It's either/or.

MR. MORENO: Right.

DR. GILCHER: We can only apply statistics to the total number.

MR. MORENO: Right. But I'm simply saying that it's a standard allocation problem. The psychology of resource allocation is such that we're aware of the person who is in need now and doesn't get it. We're not aware of those who down the line will not get something or are put at risk because of a decision we make now about a concrete individual. It's hard for us psychologically to get our heads around them.

DR. BRECHER: Celso?

DR. BIANCO: Just to emphasize one point about the precautionary principle that maybe you could have emphasized a little bit more. There is a balance between what we apply and the results of that that we often forget as we are driven towards zero risk.

Second, I think that our role as experts is confused by the question of trust that you raised, too. We have been trying to regain trust for the last 20 years, and that is the struggle. And I think that the tipping of the balance towards the zero risk is very much the result of that.

MR. MORENO: I agree.

DR. BRECHER: Larry?

MR. ALLEN: That's essentially what I was going to say, that we're dealing with two issues here: risk versus trust. And if I accept the risk of a procedure or a transfusion, then I also must trust you and the information that you're giving me prior to make taking that risk. And, historically, not just with a community like say, for example, the hemophilia community, but minority communities, that trust is not there. It essentially has never been there.

MR. MORENO: Right.

MR. ALLEN: So there's a balance that is probably impossible to meet or match. But it's still there, and it's something that we have to be aware of and accept.

MR. MORENO: I agree.

DR. BRECHER: All right. Thank you, Jon. I think we have to wrap this up.

MR. MORENO: Thank you.

DR. BRECHER: This was a good discussion, and I think your talk was right on the money as to what this committee needs to think about.

We are fortunate that Dr. Slater is here now, and she's going to be talking about the committee charter.

DR. SLATER: Good morning. I'm happy to be here. I have two minor comments other than to urge you on on this fascinating and very ambitious agenda. I will try and stay a little bit this morning. My schedule is obviously crazy, so I will not be able to join any of the discussions tomorrow, which is very regrettable, but I think through dialog with Captain McMurtry and others from HHS, I will be amply educated on the conversations from today and tomorrow.

Again, just to thank you on behalf of the Secretary for your time, your service. It's even more exemplary today given the extreme weather conditions that we have here in Washington, but again, the Secretary is very grateful to the time that you give to our government and your expertise, and we very much try and value and process your recommendations and very much respect them.

The main change from my office this year I think has to do with the input that we did provide to the revision of the charter. You all have a copy of that charter.

The revisions to the charter were routine in that, as you know, the charter of this Committee is reauthorized on a 24-month basis, so the timing of the revisions were perfectly in keeping with that, but upon my taking this office, I noted immediately that the charter needed to be altered a bit in keeping with some of the charters that we hold for some of the vaccine committees, where members of the Committee, by necessity because of their expertise, are also members of the industry that is being commented upon. And so it's very important to make sure that the charter reflects that sensitivity and that allows you then the avoidance of the appearance of conflict of interest, and really, it's the appearance of conflict of interest that is of concern.

In this, obviously, we want to avoid real conflict of interest. That was not at issue here. It's simply to protect you in the legal terminology that conforms to these charters. Any of the other wording of the charter, I'm not going to be able to perhaps respond to. Those are the lawyers who do their job very elegantly and well, and so you have all had the charter to read.

As you know, the October 9 charter now codifies the balance that we have on this Committee of consumer, academic and industry representatives. The designated industry members, as you've read, will represent the AABB, one of the two major distributors of blood, on a rotating basis, a company that produces nucleic acid tests, a company that produces local reduction processes, major hospital organization that purchases blood and blood products, and a plasma protein therapeutic association.

As was the case in the previous charter, the 18 public and industry members are voting members. The 6 Federal