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.
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