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Blood Safety Summary - November 1998

DATE: November 30, 1998

TO: Interested Parties

FROM: Stephen D. Nightingale, M. D., Executive Secretary Advisory Committee on Blood Safety and Availability

SUBJECT: Summary of Meeting


The Advisory Committee on Blood Safety and Availability met for the sixth time on November 24, 1998 at the Omni Shoreham Hotel, 2500 Calvert St. N. W., Washington, D. C. 20008. The agenda of the meeting was the Seventh Report of the House Committee on Government Reform and Oversight titled "Hepatitis C: Silent Epidemic, Mute Public Health Response." Voting members present were Drs. Caplan and Albrecht; Mr. Allen; Drs. AuBuchon, Busch, Gilcher, Gomperts, Guerra, and Hoots; Ms. Jones; Dr. Kuhn; Ms. O'Connor; Drs. Penner, Piliavin, Schiff, and Secundy; and Mr. Walsh. Ex Officio members present were Drs. Chamberland, Feigal, Goosby, and McCurdy; CAPT Rutherford; and Dr. Snyder. Consultants present were Drs. Davey and Moore. Also present were Dr. Jay Epstein, Director, Office of Blood Research and Review, Food and Drug Administration (FDA), Dr. Nightingale, CDR Lawrence McMurtry, the Deputy Executive Secretary of the Committee, and approximately sixty members of the public.

The meeting was called to order at 8:01 AM. After announcements regarding the conflict of interest statutes which governed the meeting, roll call, and welcoming remarks from Dr. Caplan, Dr. Miriam Alter of the Hepatitis Branch of the Centers for Disease Control and Prevention (CDC) reviewed the advantages and limitations of both direct notification of individuals at risk, and of general notification campaigns directed at both the public and health care professionals. She noted that current policy is to perform direct notification for recipients of blood from donors who had subsequently tested repeatedly reactive by the multiantigen screening test for hepatitis C infection that was introduced in 1992 (the second generation enzyme immunoassay or EIA-2), and general notification for those transfused prior to 1992.

Dr. Alter presented the following information. About 850,000 individuals received blood from donors who were subsequently found to be repeat reactive by the single antigen screening test for hepatitis C infection (the first generation enzyme immunoassy or EIA-1). This test was introduced in 1990 and replaced by the EIA-2 in 1992. About 10% of these recipients are still alive. About 30% of these subsequently EIA-1 repeat reactive donors were also tested by the supplemental, multiantigen, recombinant immunoblot assay (RIBA-2) test for hepatitis C infection that was licensed in 1993. About 25% of EIA-1 repeat reactive tests would be confirmed by this supplemental test. About 90% of notifications based on a subsequent EIA-1 repeat reactive, RIBA-2 confirmed donor test would be made to a recipient truly at risk. However, only around 32% of notifications based only on a subsequent EIA-1 repeat reactive, unconfirmed test would be made to a recipient truly at risk. Overall, Dr. Alter estimated that about 53% of notifications triggered by a subsequent EIA-1 repeat reactive and, when available, RIBA-2 confirmed donor test would be made to recipients whose donors were "truly anti-HCV positive". She suggested extending direct notification to all individuals who had received blood from a donor whose repeat reactive test screening test was subsequently confirmed by a supplemental test, without regard for the year in which the tests were performed.

Dr. Alter then summarized previous and planned general notification programs, including the March 1997 National Institutes of Health (NIH) Consensus Development Conference on Hepatitis C, the November 1997 CDC teleconference, the January 1998 announcement by Secretary Shalala, the February 1998 Hepatitis Summit of the American Digestive Health Foundation, the March and September 1998 Guidances published by FDA, April and July 1998 meetings at CDC, the October 1998 Morbidity and Mortality Weekly Report on hepatitis C, and the July and November mailings from CDC and FDA to health professionals. Dr. Alter noted that general notification directed at health professionals was scheduled to precede general notification directed at the public. She then outlined CDC plans for public education campaigns and for evaluation of the success of these various efforts.

Dr. Caplan complimented CDC for its educational programs directed at health care professionals, and inquired if sufficient funding were available for the public education programs. Dr. Alter responded that the answer to that question would be contingent on the evaluation of current efforts. Dr. Moore emphasized the need for more support at local levels. Dr. Epstein asked if Dr. Alter's estimates included RIBA-2 indeterminate results. Dr. Alter responded that the estimates did not, but that doing so would not affect the magnitude of the relationships she described. Dr. Penner stated that direct notification triggered by a repeat reactive EIA-1 test would involve only about 54,000 surviving individuals. Dr. Alter responded that this figure did not include families of deceased recipients. She stated further "... we feel that it's just as important for people not to receive false notification as it is for people to receive notification based on a high level of certainty." Dr. Penner also asked about notification of individuals who might not know they were transfused. Dr. Alter responded that general notification to both physicians and the public identified such individuals. Dr. Secundy asked for clarification of the time frame for implementing, evaluating, and intensifying current efforts. Dr. Alter responded that notification of transfusion services by blood establishments was to begin no later than March 1999. Dr. AuBuchon complimented CDC for their support of the efforts of the blood banking community to implement the notification process.

Dr. Paul Mied of FDA then summarized his agency's actions to implement the hepatitis C lookback, including the Guidances issued in March and September 1998. He cited the availability of the currently investigational RIBA-3 supplementary test, requests by blood organizations for additional time to complete notification, and government regulation of its own regulatory process as factors which prolonged completion of various tasks. Dr. Mied noted that FDA will continue to respond to comments on its current Guidance as it prepares a Final Rule on hepatitis C lookback. Meanwhile, the current Guidance stipulates that blood establishments should begin retrospective notification of transfusion services by March 23, 1999 and complete notification by March 23, 2000. Transfusion services should complete retrospective recipient notification within a year of receipt of a notification from a blood establishment. Recipient notification should be completed by March 32, 2001.

Dr. Mied then summarized two recent reports of lookback efforts in Quebec and in southeastern Wisconsin. In Quebec, 355 of 3197 (11%) components were traced to recipients who were tested for hepatitis C infection. Of these 355, 217 (61%) tested positive for hepatitis C infection, and of these 103 (47%) did not previously know of their infection. In Wisconsin, 9 of 319 (2.8%) components were traced to recipients who were tested for hepatitis C infection. Of these, 5 of 9 (56%) did not previously know of their infection.

Dr. Mied next summarized current responses by blood banks to recipients of blood from donors who were subsequently found to have a repeat reactive EIA-1 test. The Department of Defense (DOD) has included donors who subsequently develop a repeat reactive EIA-1 test in their lookback program. However, Dr. Mied noted that DOD blood donors are typically first-time donors, and as a result DOD has fewer lookbacks to perform. The American Red Cross presently intends to do lookback on EIA-1 repeat reactive tests that have been confirmed by an investigational RIBA-2 test. The Community Blood Center of Kansas City, MO is conducting a similar program; they anticipate this will double the volume of their lookback efforts.

Dr. Mied concluded by summarizing two previous studies of lookbacks. In San Francisco, 4.4% of 17,331 individuals notified by letter of risk of exposure to HIV-infected blood (prior to the implementation of screening of blood for HIV infection) sought testing, and in Cincinatti only 1 to 5% of a population who received general notification about hepatitis C sought testing, and only 6.2% of those individuals tested positive for hepatitis C infection.

Dr. Gomperts asked if the availability of testing had been evaluated as a constraint on response to notification efforts, and if HIV testing centers were being considered as a site for hepatitis C testing. Dr. Alter responded that the American Red Cross planned to offer free testing, and she mentioned some of the difficulties that use of HIV testing centers might create. Dr. AuBuchon noted that the Health Care Financing Administration (HCFA) had not yet required its carriers to pay for hepatitis C testing mandated by lookbacks. He also inquired about licensure of the RIBA-3 test. Dr. Busch stated that the DOD was the only program currently performing lookback triggered by unconfirmed repeat reactive EIA-1 tests; he also stated that use of RIBA-2 indeterminate results to trigger lookback would double the number of notifications, and that a RIBA-2 indeterminate result implied only a small probability of true infection. Dr. Caplan then asked about the speed at which implementation was being performed. Dr. Feigal responded that the previously mandated program was well under way. Dr. Secundy asked about enforcement. Dr. Mied responded that FDA would enforce its regulation.

Dr. Darrell Triulzi then addressed the Advisory Committee on behalf of the Interorganizational Task Force on HCV Lookback, comprised of the American Association of Blood Banks, America's Blood Centers, and the American Red Cross. He emphasized the magnitude of the task. He then requested that HCFA publish a guidance for hospitals, and that HCFA ensure reimbursement for hepatitis C testing. He supported the extension of direct notification to recipients of blood from donors whose subseqent repeat reactive EIA-1 test was confirmed by RIBA-2; but he also stated that, if lookback were extended to all recipients of blood from donors who subsequently had a repeat reactive EIA-1 test, it would be impossible to complete this task within current time frames. Dr. Triulzi requested

1. adequate time be provided if lookback is mandated for all repeat reactive EIA-1 donors;

2. licensure of the RIBA-3 confirmatory test;

3. assistance from Social Security for locating recipients;

4. assistance from state bureaus of vital statistics; and

5. coverage of testing costs by Medicare and Medicaid.

CAPT Rutherford voiced support for use of a Social Security locator service. Dr. Gilcher suggested use of the currently licensed third generation (EIA-3) multiantigen screening test to retest samples that were repeat reactive by the (EIA-1) test.

Following a break, Mr. Terry Rice of the Committee of Ten Thousand addressed the Advisory Committee. He noted that the prior experience of the hemophilia community with HIV and hepatitis C infection was the perspective from which he viewed the proposed lookback initiative, and the importance he attached to the right of members of a free society to self-determination. He supported extension of the lookback to recipients of blood from all donors who subsequently developed a repeat reactive EIA-1 test. He also requested lookback for users of plasma derivatives. He requested that leadership and direction of the lookback reside within the Department of Health and Human Services rather than industry. Finally, he thanked Congressman Shays for his concern over this issue.

Ms. Jan Hamilton of the Hemophilia Federation of America also praised Congressman Shays for his efforts. Ms. Hamilton then reviewed the history of hepatitis C lookback in the context of the 1995 Institute of Medicine report titled "HIV and the Blood Supply: An Analysis of Crisis Decisionmaking." She also supported extension of the lookback to recipients of blood from all donors who subsequently developed a repeat reactive EIA-1 test.

Mr. Donald Colborn of the National Hemophilia Foundation supported previous consumer requests to extend lookback to recipients of blood from all donors who subsequently developed a repeat reactive EIA-1 test, and to recipients of plasma derivatives as well as blood components.

Ms. Miriam O'Day of the Immune Deficiency Foundation requested that lookback include patients who receive intravenous immunoglobulins, and that studies be performed to determine if type of immunodeficiency can be associated with presentation, course, or outcome of hepatitis C infection. She also requested that studies be performed on the response by patients with different immunodeficiencies to antiviral therapy and to liver transplantation.

In the discussion that followed, Dr. Hoots supported the request for notification of hemophiliacs, patients with von Willenbrand's disease, and other users of plasma derivatives by noting that, because of severity of disease, geography, or personal preference, not all such individuals regularly access comprehensive care programs. Drs. Penner and Caplan questioned the applicability of past studies of lookbacks to the current situation, particularly in view of better treatments now available. Mr. Allen stated that, as a representative of a family with members who would be targets of direct notification, he would rather get a notification that at some point turns out to be negative rather than not be part of the process at all. Mr. Allen stated that an arbitrary decision about who should be notified, and who should not, would compromise public trust. Dr. Caplan asked Dr. Harold Margolis of CDC about the adequacy of current funds budgeted for hepatitis C-related activities. Dr. Margolis responded that his greatest concern was support for programs at the state and local levels. Dr. Kuhn asked if some of the resistance to lookback was generated by fear of litigation, and whether a compensation program analogous to the Vaccine Injury Act might ameliorate these concerns. Dr. Moore advocated a health educator in every state health department. She felt that this would be a much more effective strategy than trying to go back and base decisions on a first-generation test.

Mr. Alan Brownstein of the American Liver Foundation then addressed the panel. He noted the increasing interest in hepatitis C by the media, and he stated his concern that the Department's plans to combat the hepatitis C epidemic be implemented as quickly as possible. Dr. Albert DiBusceglie, the Medical Director of the American Liver Foundation, then reviewed recent therapeutic advances against hepatitis C infection. He recommended that direct notification be extended to individuals who received blood from a donor who subsequently developed a repeat reactive EIA-1 test. He also recommended that the government explore the feasibility of tracing recipients prior to 1998. He then urged that the CDC public education plans be implemented as soon as possible. He expressed concern that women who had undergone caesarian sections and adults who were born prematurely might not be aware of their risk of hepatitis C infection through blood transfusion.

Mr. Brownstein then returned to the podium. He proposed that at least $73 million be allocated for general notification and a comprehensive public health campaign against hepatitis C, including $20 million to help support the cost of testing. He also proposed that $404 million be allocated for research on hepatitis C over a seven year period. He concluded by reading extracts of letters about hepatitis C from Drs. Tony Rodriguez and C. Everett Koop, both of whom supported extending direct notification to recipients of blood from donors with a subsequent repeat reactive EIA-1 test.

The final speaker of the morning was Ms. Phyllis Greenberger, who supported Mr. Brownstein's call for more attention to be paid to women who had had a caesarean section. Dr. Caplan concluded the morning session by listing topics for recommendations that the Advisory Committee could consider over lunch. He suggested that any such recommendations be framed so as not to interfere with ongoing lookback efforts.

Following the lunch break, the Advisory Committee unanimously approved the following recommendations:

1. The Secretary of Health and Human Services should recommend legislation that would lower barriers to the use of federal data bases for locating individuals at risk of hepatitis C infection.

2. The Department of Health and Human Services should allocate sufficient additional resources to permit the Centers for Disease Control and Prevention to work with State and Local Health Departments to facilitate education, testing, and referral programs for individuals at risk of hepatitis C infection.

3. The Department of Health and Human Services should investigate supplemental sources of financial support to facilitate prompt completion of targeted lookback for individuals at risk of transfusion-transmitted hepatitis C infection.

4. The Health Care Financing Administration should remove financial barriers to testing of individuals identified by current government standards as being at risk of hepatitis C infection.

5. The Secretary of Health and Human Services should take all necessary steps to insure completion of current lookback programs within currently recommended time frames.

6. The Advisory Committee on Blood Safety and Availability supports Recommendation 1A and 3 of the Seventh Report of the House Committee on Government Reform and Oversight.

At this point the Chairman recognized Dr. Nicole Lurie, the Principal Deputy Assistant Secretary for Health. Dr. Lurie remarked that in all the time she had been doing public health and health policy, she had never encountered an issue that has been as emotionally contentious as the hepatitis C lookback. She encouraged the Advisory Committee to identify a resolution of this issue that was science-based and in the best interest of the public's health.

The Advisory Committee then considered the following motion, which was introduced by Dr. Penner and seconded by Dr. Schiff.

7. The current targeted lookback program should be expanded to include recipients of blood from donors subsequently identified as repeat reactive by the single antigen (EIA-1) screening test for hepatitis C infection that was licensed in 1990.

In the discussion that followed, Dr. Epstein observed that the net effects of this proposal would be to double the size of the direct notification program, and to reduce the yield from 9.7% for confirmed test results to 1.5% for unconfirmed test results. Dr. Davey supported the alternative suggestion of the Interorganizational Task Force on HCV Lookback, which was to extend notification to recipients of blood from a donor whose subsequent repeat reactive EIA-1 test was confirmed by a supplementary test. Dr. Caplan asked the Advisory Committee to consider whether, if their child had been transfused between 1990 and 1992, they would like to know whether that donor had subsequently had a single antigen repeat reactive screening test for hepatitis C infection. Dr. Gomperts responded that he would test the child for hepatitis C infection regardless of the outcome of the screening test. Drs. Piliavin and Secundy agreed with Dr. Gomperts. Dr. AuBuchon proposed that the Advisory Committee support the recommendations of the CDC. Mr. Allen supported the motion as stated. Dr. Moore felt that the spirit of the House report, that people who have received transfusions get tested, could be achieved by insuring that proposed public education programs were implemented.

Dr. Piliavin raised concern about those, who she estimated at 25% of people, who would be falsely reassured by a negative test. "The only fair thing," Dr. Piliavin said, "is to put a lot of effort and funding into finding people who were transfused before 1992 and forget about this testing thing." Dr. Penner disagreed, stating that the EIA-1 test was not substantially less sensitive than subsequent screening tests. Dr. Penner also noted that estimates of the percentage of individuals with hepatitis C infection that would be identified by a lookback triggered by a repeat reactive EIA-1 test had risen from 1% to between 30 and 50%.

Dr. Gilcher suggested extending lookback to recipients of blood from donors whose screening test is repeat reactive at their first encounter with one blood establishment, but whose screening test was negative when they previously donated blood at other blood establishments. He also suggested extending lookback to recipients of blood from donors with no subsequent screening test result who are identified when a recipient with no risk factor other than transfusion is subsequently diagnosed with hepatitis C infection. Dr. Guerra raised concern for those recipients unable to pay for their own testing for hepatitis C infection. Dr. Chamberland anticipated that the question of lookback would arise again for other pathogens, and expressed hope that the precedent set by the Advisory Committee would be consistent with good public health policy; Dr. Hoots concurred with this. Dr. Goosby felt that preservation of the trust between the patient and the provider, or health care system, was the critical element in his own decision process. Dr. Caplan stated that his support for the motion was based on the persistent support of patient communities for it, and the issue of trust between patient and provider.

Dr. Feigal reminded the Advisory Committee that implementing lookback through FDA regulation implied that if blood establishments or transfusion services could not comply with the regulations within the allotted time frames, they would be closed. Dr. Secundy, Dr. Piliavin, Mr. Walsh, Ms. Jones, and Ms. O'Connor all expressed concern for those who would not be identified by a targeted lookback. They expressed support for direct notification of all individuals who had received a transfusion prior to 1992. Dr. Gilcher pointed out that this effort would be constrained by the limited retention of medical records prior to that date. Dr. Secundy requested clarification from Dr. Feigal of his previous remarks. Dr. Caplan then called the vote.

The vote was 10 in favor (Dr. Albrecht, Mr. Allen, Dr. Guerra, Dr. Hoots, Dr. Kuhn, Ms. O'Connor, Dr. Penner, Dr. Schiff, Dr. Secundy, and Mr. Walsh), 5 opposed (Dr. AuBuchon, Dr. Busch, Dr. Gomperts, Ms. Jones, Dr. Piliavin) and one abstention (Dr. Gilcher). The motion was approved.

Following the vote, Dr. Gilcher said he would have supported the motion if it had been for direct notification of individuals who received blood from a donor whose repeat reactive EIA-1 test had been confirmed by a positive supplemental test. Dr. Piliavin said she would have supported that motion. Dr. Secundy said she would have supported that motion as well. Dr. Piliavin asked Dr. Secundy if she wished to ask for a re-vote. Dr. Secundy declined to do so.

Dr. Secundy then moved that the Department of Health and Human Services support CDC efforts to develop public service announcements and other communication strategies for all recipients of blood or blood products of their risk of hepatitis C infection. Dr. Busch noted that the Advisory Committee might consider other strategies for implementing a lookback triggered by a repeat reactive EIA-1 test. He then stated that he had data which he could present "... that would show if we simply use the reactive ratio of the screening test, we could capture 90-plus percent of the confirmed positives and avoid notifying approximately 70 percent of the false positives. Dr. Schiff then seconded Dr. Secundy's motion. Dr. Epstein stated that the motion was for things that were already being done. Dr. Secundy stated that her concern was for individuals not reached by previous efforts. Dr. Guerra informed the Committee that local health departments were developing programs to reach individuals outside traditional systems of care, which was the concern on which Dr. Secundy's motion was based. Dr. Caplan asked Dr. Secundy if she would withdraw her motion, and she agreed to do so.

Dr. Caplan then asked the Committee if it wished to review various strategies for implementation of a first-generation lookback prior to its implementation. Dr. Busch noted that the current resolution would require direct notification even if a supplemental test was negative. He also noted that donors who subsequently tested negative may have seroreverted between the time of their single antigen, repeat reactive test and their recall for a supplemental test. Dr. Busch then moved, and Dr. AuBuchon seconded, the following motion:

8. Implementation of the prior motion should be deferred until the Public Health Service has had an opportunity to review it and to present options for its implementation and evaluation to the Advisory Committee at its next meeting.

The motion was approved 15 to 1, with Dr. Secundy dissenting.

Dr. Nightingale stated that it was ordinary practice for committees to keep the record of a meeting open for a period of time so that members could add supplemental testimony to it, and he urged members, including ex officio members, who wished to pursue discussion of various implementation strategies prior to the next meeting that they do so through this mechanism. Dr. Nightingale then summarized other issues that might be brought before the Committee, including leukodepletion, geographic-based donor deferrals, other transfusion-transmissible agents, an updated National Blood Policy, and the continuing shortage of plasma derivatives.

The meeting was then adjourned at 3:28 PM.

This Summary of Meeting was approved by the Chairman, Dr. Caplan, on November 30, 1998.