Donor Screening and Deferral
The purpose of donor screening and deferral procedures is to minimize the possibility of transmitting an infectious agent from a unit of donated blood to the recipient of that unit, as well as ensuring the welfare of the donor himself. Donor screening and deferral includes measures taken prior to and during the collection of blood or plasma. Specifically, donor screening includes the identification of suitable donors; the exclusion of high-risk groups (e.g., prisoners); use of questionnaires, interviews, and medical exams at the time of donation; and providing donors with the opportunity to self-defer by privately coding the unit label as "do not transfuse" or "not for transfusion" (self-deferral is discussed in detail at the end of this chapter). Donor screening also includes laboratory tests performed on the unit of blood collected for the presence of markers of infectious disease. Two types of tests can be used to detect an infectious agent; a surrogate test (e.g., antibody to hepatitis B core) or a direct test for the virus (anti-HIV using the ELISA test as of March 1985; see Chapter 3). These tests are performed because donors may be unaware that they are asymptomatic carriers of an infectious agent or may be unwilling to identify themselves as a member of a high-risk group. Donor deferral is the temporary or permanent rejection of a donor, based on the results of the screening measures listed above.
By January 1983, the CDC had accumulated enough epidemiological evidence to suggest that the agent causing AIDS was being transmitted through blood and blood products, and also through sexual contact. The evidence also demonstrated that there were several groups in the United States with an increased risk for developing AIDS. The highest incidence of the disease was
reported in male homosexuals, who were donating blood frequently in some geographic regions. In the early 1980s, the increased evidence of infections in IV drug users suggested that AIDS was an infectious disease similar to hepatitis B in modes of transmission. As a result, debates began regarding the possibility of increasing the safety of the blood supply through the exclusion of high-risk groups as blood and plasma donors. This chapter describes donor screening and deferral measures before the test for HIV (ELISA) became available in 1985 and addresses whether the actions taken were reasonable given the information available at the time.
Donor screening issues arose in mid to late 1982, when the first cases of AIDS in hemophiliacs were reported and the first possible case of transfusion-associated AIDS was reported in an infant (CDC, MMWR, July 16, 1982; CDC, MMWR, December 10, 1982). As a result, the blood bank community began discussing the costs and benefits of several types of donor screening measures in late 1982 and early 1983. Between December 1982 and December 1983, there were two critical events that presented opportunities for the blood services community to enact new donor screening and deferral policies to reduce the threat of HIV transmission through blood and blood products.
Critical Event 1
On January 4, 1983, the Public Health Service (PHASE) held a meeting convened by the CDC in Atlanta on opportunistic infections in hemophiliacs. At the meeting, the blood services community first heard preliminary data on the possibility of a transmissible agent within the blood supply. Scientists from the CDC recommended that blood banks implement specific donor screening measures such as questioning donors about their risk behaviors and running blood donations through a series of tests, among which the most important was for the hepatitis B core antibody insofar as it occurred in most individuals who had AIDS (Curran, Evatt, Foege, McAuley, Pindyck, Rodell interviews; Foege, 1983). There was broad resistance to the implementation of specific donor screening measures, and the meeting ended with no consensus on the validity of such measures for the exclusion of high-risk donors.
Critical Event 2
On December 15-16, 1983, the Blood Products Advisory Committee (BPAC) of the FDA met to discuss, in detail, all possible options of surrogate marker tests for HIV (see also Chapter 3). This meeting is notable for being a second attempt to address the need to implement surrogate tests as a means to increase the safety of the blood supply and a second occasion when testing was proposed but not recommended.
The Committee identified three hypotheses to guide its analysis of the issues of donor screening and deferral:
There was a lack of consensus about the costs and benefits of implementing various donor screening procedures as a means to reduce the risk of transmission of HIV through the blood supply, which resulted in limited responses among organizations to the issues of donor safety.
Information available at the time might have been sufficient to convince blood and plasma collectors of the need to directly question donors about their risk behaviors (e.g., sexual preference, drug use) or to use anti-HBc testing as a means to exclude high-risk donors, but other constraints in the environment in which they operated prevented the collectors from implementing a specific policy in the early 1980s.
Inappropriate incentives inhibited reasonable decisionmaking by the responsible parties.
Testing these hypotheses against the documentary and personal evidence, the Committee concluded that they were able to support the first and second hypotheses, but unable to support the third. Before turning to a detailed examination of these conclusions, we present a brief history of donor screening practices.
DONOR SCREENING PRACTICES
Cases of post-transfusion hepatitis were described as early as 1943 (Bensen 1943) and syphilis screening tests were introduced in 1946. In 1965, identification of the virus causing "serum hepatitis" led to a direct test for the
presence of an antigenic component of the virus. Prior to 1970, the incidence of post-transfusion hepatitis was 8-17 percent among transfusion recipients (Seeff 1988). During the period from 1970-1972, all blood and plasma collection agencies implemented the test for the presence of hepatitis B virus. Subsequently, hepatitis cases continued to appear in approximately 5-18 percent of transfusion recipients (OTA 1985), strong evidence that viruses in the blood supply other than hepatitis B caused hepatitis (non-A, non-B hepatitis).
In the late 1970s and early 1980s, blood donor pools included many groups at high risk for AIDS. The homosexual population volunteered to donate blood frequently during this time frame in efforts to help develop a hepatitis B vaccine and to gain a social acceptance (Evatt, Curran, McAuley, Perkins interviews). In addition to homosexuals, other populations who were at a high risk for infectious diseases, such as prison inmates and persons in other institutional settings (e.g., mental hospitals), served as blood or plasma donors (McAuley, Perkins, Rodell, Shanbrom interviews). People in these groups constituted a large proportion of the paid donors in the United States. Thus, both the paid and volunteer donor pool included many individuals from the high-risk populations.
Early Donor Screening Practices
Efforts to have "safe" donors started in the early 1950s. The aim was to eliminate persons who carried the two known blood-borne infectious agents, those causing syphilis and hepatitis. Blood bank personnel obtained every donor's medical history and deferred any donors who had a history of hepatitis. Blood from volunteer donors was known to be safer than blood from paid commercial donors (Allen, et al. 1959; Eckert 1986). In July 1973, the Secretary of Health, Education and Welfare called for a transition to an all-volunteer blood donation system (for whole blood) as part of a national blood policy. In November 1975, the FDA required that all blood units collected be labeled as from either a paid or a volunteer donor (U.S. Comptroller General 1975). At this time (and currently), paid donors were the principal source of plasma for fractionation into blood products such as AHF concentrates.
In 1982 the American Association of Blood Banks (AABB) standards required that each donor meet the following criteria: the donor had to appear in good health, the skin at the venipuncture site had to be lesion-free, the donor should not have received blood or blood components (known to be a possible source of hepatitis) in the preceding six months, and the donor's arms had to pass inspection for repeated sites of venipuncture prior to donation. In addition,
the standards required permanent deferral of a donor if the donor had a history of viral hepatitis, a history of reactive tests for hepatitis B surface antigen, or had donated the only unit of blood or blood components transfused to a patient who developed post-transfusion hepatitis within the six months following transfusion. Recent travel to areas considered endemic to malaria led to deferral for six months after return, and donors with clinically active hepatitis were unacceptable (AABB 1982). These standards applied to American Red Cross collection centers and to all other community blood banks that were members of the AABB.
In 1982 the AABB required that all its member blood collection sites perform the following tests on each unit collected: determination of ABO type, determination of Rh type, tests for "unexpected antibodies" prior to cross-match, tests for hepatitis B surface antigen, and a confirmatory test on blood type and Rh type after labeling the unit to discover any labeling errors (AABB 1982).
ANALYSIS AND FINDINGS
January 4, 1983, CDC Meeting
As a follow-up to meetings in July 1982 (see Chapter 3), the meeting in Atlanta on January 4, 1983, was convened to consider opportunities to prevent AIDS transmission, both person-to-person, and through blood and blood products. This meeting was widely publicized, and over 200 people attended, including representatives of the CDC, the FDA, NIH, the National Hemophilia Foundation, the National Gay Task Force, blood banks, and the plasma fractionation industry. While there was a consensus among most plasma and blood collection organizations and PHS agencies that steps should be taken to reduce the risk of AIDS transmission through the blood supply, members of the scientific and medical community disagreed on measures for detecting high-risk donors.
William Foege, director of the CDC, opened the meeting, which was chaired by Jeffrey Koplan, assistant director for public health practice at the CDC. James Curran and Bruce Evatt of the CDC presented data they had collected on AIDS in hemophiliacs and transfused patients. They concluded that AIDS was transmitted by sexual contact and through blood (Curran, Evatt, Foege interviews). They also stated that this infectious agent might have entered the blood supply through donations from infected people, particularly male homosexuals. By January 1983 more than 700 cases of AIDS had been reported, of which approximately 70 percent were in homosexual men. The CDC officials suggested changing the donor screening process to identify homosexual donors
with multiple sexual partners by asking male donors whether they had ever had sex with a man (Foege 1983).
At the meeting, CDC scientists also recommended performing a surrogate test for AIDS (to detect antibodies against hepatitis B core antigen) on all blood units. Surrogate testing is "the use of nonspecific laboratory markers" to detected infectious agents that show a correlation with HIV infection. The CDC predicted that implementing the anti-core test for hepatitis B would detect 90 percent of donors with AIDS. There was no agreement that the test would be effective, and there was no consensus to use it.
Outcomes of the Meeting
A series of responses followed the meeting. On January 6, 1983, Donald Francis, assistant director for medical science of the Virology Division at the CDC, wrote a memo to Dr. Koplan, stating that the CDC should proceed to promulgate its recommendations in the hope that the FDA would agree. One of the CDC recommendations was deferral of all blood and plasma donors who
are IV drug users (already in place);
are sexually (heterosexually or homosexually) promiscuous (more than an average of two different people per month for the previous two years);
have had sexual (heterosexual or homosexual) contact with someone who is sexually promiscuous or an IV drug user in the past two years;
have lived in Haiti in the past five years; and
have a serologic test positive for anti-HBc.
Francis estimated that this deferral process would eliminate over 75 percent of AIDS-infected donors (Francis 1983).
The blood banks (American Association of Blood Banks, American Red Cross, and Council of Community Blood Centers) issued a joint statement entitled "Acquired Immune Deficiency Syndrome Related to Transfusion" on January 13, 1983. They recommended that donor screening include specific questions to detect early symptoms of AIDS or exposure to patients with AIDS, but they did not recommend asking about high-risk sexual practices. The joint statement addressed the question of whether it was appropriate to limit voluntary blood donation from groups at high-risk for AIDS, and pointed out that this question involved many medical, ethical, and legal issues that were not easily resolved. The recommendations held that despite pressure on the blood banks to restrict blood donation by gay male donors, "direct or indirect questions about a donor's sexual preference are inappropriate." The joint statement also encouraged the use of autologous donations, especially in elective surgery, and
called upon blood banks to prepare to handle increased requests for cryoprecipitate (AABB, et al. 1983).
During the early months of 1983, prior to any PHS recommendations, many blood banks added to their donor questionnaires inquiries about symptoms associated with AIDS, such as presence of enlarged lymph nodes, night sweats, and weight loss. On January 14, 1983, the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation (NHF) recommended that the plasma product industry take steps to eliminate high-risk donors (e.g., IV drug users, homosexuals) from plasma donation. The plasma fractionators began questioning donors and excluding high-risk donors in the first months of 1983, but did not implement surrogate testing (NHF 1983).
The American Blood Resources Association (ABRA), a trade organization for the manufacturers of blood products, issued its recommendations on donor deferral on January 28, 1983. One of the three focal areas of ABRA's recommendations was surrogate laboratory testing. At the time, ABRA recommended against large scale surrogate testing pending an assessment of the issues underlying the implementation of surrogate testing, specifically determining "the adequate availability of testing reagents and equipment of any of the several possible tests under consideration, their economic and logistical impact upon the plasma supply network, the efficacy of the test to exclude high-risk individuals, and other potential consequences to plasma products resulting from the imposition of additional testing requirements" (ABRA 1983).
The PHS promulgated its first official recommendations on the prevention of HIV on March 4, 1983. Individuals at high risk for AIDS were required to refrain from donating plasma and/or blood. Persons at increased risk of AIDS included the following:
persons with symptoms and signs suggestive of AIDS,
sexual partners of AIDS patients,
sexually active homosexual or bisexual men with multiple partners,
Haitian entrants to the United States,
present or past abusers of IV drugs,
patients with hemophilia, and
sexual partners of individuals at increased risk for AIDS.
Prior to the issuance of these recommendations, donor selection policies (AABB 1982 Standards for Transfusion Services) for both the collection of whole blood and plasma already sought to identify people in the following high-risk groups as being at increased risk of infectious diseases: drug abusers, persons with residence in or recent travel to Haiti, and those with a history of recent treatment with blood products. The PHS made the following new recommendations for preventing transmission of AIDS through blood and blood products:
Sexual contact should be avoided with persons known to have or suspected of having AIDS.
Members of groups at increased risk for AIDS should not donate blood and/or plasma; centers collecting plasma or blood should notify donors of this recommendation.
Studies should be conducted to evaluate screening procedures, including lab tests and physical examinations, for their effectiveness in identifying and excluding plasma and blood with a high probability of transmitting AIDS.
Physicians should adhere strictly to medical indications for transfusions and encourage autologous donations.
Work should continue toward development of safer blood products for use by hemophilia patients.
The PHS did not recommend directly questioning donors about high-risk sexual behavior nor did it recommend surrogate testing of donated blood (CDC, MMWR, March 4, 1983).
Later in March 1983, the FDA notified all establishments collecting source plasma and whole blood for transfusion, and manufacturers of plasma derivatives, of the steps needed to decrease the risk of blood or plasma donation by persons who might be at increased risk of transmitting AIDS. The FDA advised the blood and plasma facilities to train personnel who screen donors to recognize the early signs of AIDS and to establish educational programs to inform persons at increased risk for AIDS that they should stop donating. The FDA issued three letters on the reduction of the risk of transmission of HIV through blood and blood products (see Appendix D for the text of these letters, and Chapter 6 for further discussion). The letters recommended the following steps for whole blood and plasma collection centers:
educational programs should be instituted to inform persons at risk of AIDS that until the AIDS problem was resolved or a definitive test for AIDS became available, they should refrain from donating blood;
personnel responsible for donor screening should be retrained to recognize signs and symptoms of AIDS; and
the standard operating procedure should include the quarantine and disposal of any products collected from a donor that was known to have AIDS or was suspected of having AIDS (Petricciani 1983a,b).
The following additional steps applied only to plasma collection centers:
if plasma was collected from a donor belonging to a high-risk group, label each unit to identify it for restricted use only;
examine donors for lymphadenopathy; and
keep an accurate record of each donor's weight and monitor for significant weight loss (Petricciani 1983c).
These advisories constituted an interim measure to protect recipients of blood and blood products until specific laboratory tests became available.
The FDA recommendations for plasma fractionators stated that ''extensive discussions among licensed manufacturers, the Office of Biologics and concerned groups such as the NHF, have led to a consensus concerning an appropriate approach to decreasing the potential risk of transmitting AIDS by certain plasma derivatives." The recommendations included (a) do not fractionate plasma collected from donors at increased risk of AIDS into derivatives already known to have a high risk of disease transmission; (b) use plasma from donors in high-risk groups only for the manufacture of albumin, plasma protein fraction, globulin, or in vitro diagnostic products; and (c) all establishments must label products containing plasma proteins from high-risk donors with "caution, for use in …" (Petricciani 1983c). The memo made the restrictions effective immediately. Although the FDA did not call the recommendations in these letters regulations, blood and plasma collection organizations promptly implemented them (Bove, Perkins, Petricciani, Sandler interviews).
Donor Questioning and Opposition to It
A representative from Alpha Therapeutics, a commercial manufacturer of AHF concentrate, announced at the January 4, 1983, meeting that the company had instituted direct donor questioning designed to exclude high-risk individuals from plasma donation. On December 17, 1982, Alpha Therapeutics had required the exclusion of all donors who had been in Haiti, used IV drugs, or, if male, had had sexual contact with another man. The announcement of this action met with a great deal of opposition from many groups, including the volunteer blood banks and the gay community. These groups took the position that donor sexual preference was a private matter and that the questionnaire was an invasion of privacy. Additionally, Alpha Therapeutics took the position at the January 4, 1983, meeting that AIDS should be a reportable disease, in order to assist in donor screening (Alpha Therapeutics 1994).
Representatives from other plasma fractionation companies also present at the January 4, 1983, meeting discussed the potential threat to the safety of plasma and their manufactured products. One representative from the Pharmaceutical Manufacturers Association stated: "The fractionation industry voluntarily led the way several months ago in designing and implementing donor-processing programs that were aimed at minimizing participation in plasma collection by members of AIDS high-risk groups. By the early part of
1983, each of the companies … had in place donor education and questioning programs specifically requesting members of high-risk groups to identify themselves and refrain from donating plasma" (FDA, BPAC 1983a). One explanation for the plasma fractionators' aggressive approach to donor screening may have been the profit motive that drives one company to distinguish itself from its competitors. Executives at Alpha Therapeutics and other companies may have acted upon their belief, or strong suspicion, that AIDS was caused by a blood-borne infectious agent, and as a result implemented screening policies to protect both their company from product liability and the recipients of their products from harm. In addition, Alpha's insistence on the exclusion of high-risk donors in late 1982 may have led other companies, which did not want their products to appear less safe than Alpha's, to implement donor screening policies in 1983.
Some nonprofit blood centers initiated projects directed towards excluding donors or removing infected blood from the available supply. For example, by February 1983, the Greater New York Blood Program was providing donors with information about AIDS, high-risk groups, and the possibility of transmitting AIDS through blood. They asked donors either not to give blood or to give it for research purposes if they identified themselves as a member of a high-risk group (self-deferral). Medical screening resulted in the deferral of an additional 2 percent of donors, and a confidential questionnaire resulted in self-deferral by 1.4 percent of the donors (Pindyck, et al. 1985). The prevalence of anti-HBc in the group who indicated their blood was for research only was approximately 12 percent, compared to 6 percent among those donations marked for transfusion. These gains were weighted against the estimated cost of the anti-HBc test ($3.00 per test) and the cost of discarding a unit and replacing a donor (FDA, BPAC 1983c; Pindyck, et al. 1985). As a result, the New York program relied on "confidential unit exclusion" as a safety measure, rather than implementation of a routine anti-HBc surrogate test. (Confidential unit exclusion involves use of a bar code sticker to label a unit "do not transfuse" or "not for transfusion.'' See Afterward below.)
Although blood banks did not implement direct questioning of donors about their sexual preferences at the same time plasma collectors did, they did comply with the FDA's recommendations issued on March 4, 1983. These recommendations included the following steps: to expand medical screening of donors, to provide written educational materials to donors about those groups at increased risk of AIDS and the necessity of refraining from donation if identified as a member of the high-risk groups, as well as allowing for individual methods (e.g., confidential unit exclusion) for confidential self-deferral (OTA 1985).
Some people viewed direct questioning about sexual behavior and drug use as a violation of an individual's right to privacy. Public health officials countered by saying that the individuals' rights were less important than the
collective public health. Many in the gay community objected to direct questioning and donor deferral procedures as discriminatory and persecutory. Many in the blood bank community questioned the appropriateness of asking direct or indirect questions about a donor's sexual preference (Bove, Curran, Evatt, Foege, Sandler interviews). Other individuals and organizations were concerned about providing the public with information about AIDS that might scare them away from donating blood (Curran, Evatt, Foege interviews). The National Hemophilia Foundation, physicians, and hemophilia treatment centers were concerned about AHF concentrate shortages and favored conveying a "let's not panic" attitude to the public (Curran interview).
The blood banks began with the view that a volunteer blood donor is an altruistic person who, despite the inconvenience, takes the time to donate blood. The idea of confronting such a donor with a prying and personal question about his sexual behavior seemed reprehensible and potentially very damaging to donor motivation (Bove, Sandler interviews). In addition, the blood banks perceived that the gay community might not cooperate if gay donors were rejected on the basis of sexual orientation, and furthermore, that they might donate on purpose or out of spite (Evatt, Silvergleid interviews). Because of their fear of blood shortages, the blood banks strongly opposed implementation of direct questioning. It appears that they decided that informal, "out of the spotlight," negotiations with the gay community were more likely to reduce the number of high-risk donors then implementing direct questioning of donors (Bove, Curran, Evatt, Sandler interviews). As one blood banker representative expressed it, "direct questioning will be counterproductive in most ARC regions, given the public nature of the blood donation process. How many men … are going to step forward, out of their closet, in front of their peers and admit they are 'queers'? Or even call in later to have their donation discarded" (Cumming 1983).
With respect to hepatitis, donor selection practices had changed in late 1982 and early 1983 to restrict donations by some populations with a prevalence of hepatitis B greater than the general population (e.g., prison inmates). Although there was recognition that the male homosexual population had a prevalence rate of infection with hepatitis B that exceeded the prevalence rate in the prison population, homosexual men were not included in the exclusionary criteria (Dodd 1982). No one articulated a convincing rationale for failing to exclude the donor group with the highest prevalence of hepatitis (i.e., male homosexuals) while acting swiftly to exclude other groups (Haitians) whose prevalence was lower.
Prior to the January 4 meeting, the CDC had worked with gay groups to enlist their support for deferring from blood donations (Curran, Evatt interviews). By early 1983, the male homosexual population had established groups that defended their interests in the political arena. Spokespersons for some of these groups were present at the Atlanta meeting and appeared to
express concerns that any restriction on blood donations by male homosexuals would be a form of discrimination. Although some representatives of gay groups characterized male homosexuals as willing to undergo testing of donated blood (but not questioning of donors about sexual preference), some expressed doubts that homosexual males would answer direct questions about sexual activities truthfully, in light of the stigma attached to homosexuality (Foege 1983). Representatives of the National Gay Task Force opposed the suggestion to defer homosexual men. The CDC took the position that donor screening procedures were the only way to minimize the risks of infection at the time (Evatt interview).
In sum, the plasma fractionators favored donor questioning as a way to protect their products, and the users of their products from harm and, possibly, to protect themselves from product liability. The gay community saw donor questioning as an infringement of their rights. The CDC viewed it as the sole means of protecting the public health at the time. The blood banks saw donor questioning as damaging to donor motivation and possibly counterproductive to risk reduction. Generally, decisionmakers who did not insist upon direct questioning of donors had several reasons: they were unsure of the propriety of asking donors about sexual activities; they did not believe that direct questions would obtain reliable answers from donors about a sensitive issue such as sexual behavior; and they were concerned about the legal and political ramifications of direct questioning (see for example, American Red Cross memo from Dr. Cumming to Mr. de Beaufort, February 5, 1983, enclosed in Appendix D).
Surrogate Testing and Opposition to It
At the January 4, 1983, Atlanta meeting, CDC scientists also recommended testing all blood units with an anti-HBc test, predicting that the anti-core test for hepatitis B would detect 90 percent of donors with AIDS.
Published data on the accuracy of surrogate marker testing varied in the reported proportion of AIDS patients who had positive tests for anti-HBc. Unpublished data presented by the CDC showed a high prevalence of anti-HBc in AIDS patients, based on data from a cohort of homosexual men with AIDS who attended a sexually transmitted disease (STD) clinic (Foege 1983). Data from several studies based on different groups resulted in findings dissimilar from those reported by the CDC. These studies estimated that the implementation of anti-HBc would detect only between 25 percent and 40 percent of blood donors with AIDS (Foege 1983; Bove, Pindyck interviews). These studies suggest that there may have been variations between groups from different geographic areas. The Irwin Memorial Blood Bank conducted a pilot test on anti-HBc and found a higher correlation between ethnicity and prevalence of hepatitis B than between homosexuals and hepatitis B. The significance of
such data did not clearly illustrate the benefit of using the test as a means to identify donors at high risk of transmitting AIDS (Perkins, Pindyck interviews; FDA, BPAC 1983c).
A careful reading of the evidence shows why people could not agree about the frequency of anti-HBc in people who could transmit AIDS. The CDC claimed that 90 percent of AIDS patients had anti-HBc. This statement appeared in public statements and letters, but the Committee was unable to find any 1982-1984 account that described the clinical characteristics and size of their AIDS study population, the methods for measuring anti-HBc, or a table of results. In other words, the standard basis for evaluating a scientific claim, a published report, was missing.
Because those that claimed a much lower impact on anti-HBc published their work, it is possible to evaluate its relevance to preventing the transmission of AIDS by excluding donors who had anti-HBc. These investigators described the frequency of anti-HBc in various high-risk groups (homosexuals, donors who designated their blood for research rather than transfusion, and residents of San Francisco census tracts that had a high proportion of homosexual men). Of course, only a fraction of these populations were infected with HIV. Therefore, the prevalence of anti-HBc in these high-risk populations would be much lower than in a population of people infected with HIV.
In early 1985, the CDC did publish a well-designed study that showed that 62 percent of donors to whom the CDC had traced a transfusion-related AIDS case had anti-HBc (McDougal, et al. 1985). The ELISA test and the Western Blot would be available within a few months (the 1985 article contained the results of using the ELISA and Western Blot to test their study subject's serum for HIV), and a surrogate test for HIV infection was no longer needed. When it was important to know the effect of surrogate testing on AIDS transmission, however, the evidence was inadequate or unpublished. Apparently, no one examined the evidence from all these studies and did what is commonplace in the mid-1990s: to dismiss conclusions based on inadequate evidence and call for well-designed studies. Those who used inadequate or unpublished evidence to support their position were not called to account, and disputants could not agree on a policy for surrogate testing.
Discussions among the CDC's AIDS Working Group in early 1984 concluded that instituting anti-HBc testing would lead to exclusion of far more donors than would be expected to (or actually) have AIDS. If the test were implemented, its primary benefit would have been to allay patient's and physician's fear of AIDS, not to significantly reduce exposure to AIDS (OTA 1985). Thus during the early debates surrounding the issue of whether or not to use the test for anti-HBc as a means to reduce AIDS transmission, knowledge about the usefulness of the test was inconsistent and the value of the test was highly uncertain. The Committee found no evidence that an evaluation was ever undertaken to systematically examine these differences and to determine the
utility of the test. In the Committee's view, evidence suggested there were differences geographically that may have made the test more useful in some areas of the United States than in others.
The disagreements about the benefits of surrogate testing resulted in the rejection of the recommendation to implement surrogate testing. There were several reasons behind this decision, including
the cost of the test;
the availability of the surrogate test;
uncertainty as to the usefulness of the anti-HBc test as a screening measure for donors at risk of having AIDS; and
the fact that the test was not an AIDS test, and that, as the cause and treatment of AIDS was not yet known, the notification of deferred donors as to why they were deferred would be difficult (Bove, Perkins interviews; FDA, BPAC 1983c).
The blood bank community believed that implementing surrogate testing while there was no specific test for AIDS would appear discriminatory and would result in discarding much noninfectious blood. Blood bank physicians raised doubts about the usefulness of the anti-core test for hepatitis B for three reasons. They questioned the validity of the CDC data on the correlation of anti-HBc to AIDS cases among a cohort of homosexuals who attended an STD clinic. They were concerned about donor attrition, which they estimated at over 5 percent among volunteer donors and up to 20 percent among commercial donors, which in turn could lead to serious blood shortages. Finally, some raised the concern that eliminating donors with the protective antibody for hepatitis B could endanger the blood supply, especially for plasma derivatives like gamma globulin (Perkins, Rodell, Sandler interviews). In addition, many believed that blood banks that performed surrogate testing (e.g., Stanford University in 1983) for HIV would attract high-risk donors who wanted to be tested to see if they were infected (Curran, Evatt, Francis, Perkins, Silvergleid interviews), which would decrease the safety of the blood supply (Bove, Sandler interviews; Doll, et al. 1991). At the time, there thus appeared to be within the blood bank community both many who feared for the safety of the blood supply if surrogate testing were implemented, and some who did not view the possibility of an infectious agent in the blood supply as great enough to warrant such testing. The FDA did not mandate screening for hepatitis B core antibody until the late 1980s as a surrogate test for non-A, non-B hepatitis (CCBC 1994; Evatt, Perkins interviews).
Criticism of the CDC's Data and Motives
Participants in the Atlanta meeting and others in key decisionmaking roles expressed reservations about the validity of the CDC data, as they did not believe the CDC to be a credible source of information regarding AIDS (Donohue, Gallo interviews). Some perceived the CDC's urgency regarding AIDS as a self-serving strategy to ensure its (CDC's) survival. A January 26, 1983, interoffice memo of the American Red Cross stated:
CDC is likely to continue to play up AIDS—it has long been noted that CDC increasingly needs a major epidemic to justify its existence … especially in light of Federal funding cuts … AIDS probably played some positive role in CDC's successful battle with OMB to fund a new $15,000,000 virology lab. This CDC perspective is also obvious from the general "marketing nature" of the January 4, 1983 … meeting. … We can not depend on CDC to provide scientific, objective, unbiased leadership on the topic. … Because CDC will continue to push for more action from the blood banking community, the public will believe there is a scientific basis and means for eliminating gays. … To the extent the industry (ARC/CCBC/AABB) sticks together against CDC, it will appear to some segments of the public at least that we have a self interest which is in conflict with the public interest, unless we can clearly demonstrate that CDC is wrong [Cumming 1983].
In particular, as stated earlier, blood bank physicians questioned the validity of the CDC data on the correlation of anti-HBc to AIDS cases among a cohort of homosexual who attended an STD clinic.
Erroneous assumptions about the incubation period and the mortality rate for AIDS led to widely differing, inaccurate projections of the outcome of more vigorous donor screening. Some of the key decisionmakers relied upon their knowledge of the epidemiology of other viral disease to guide them in developing prevention and control measures. For example, it was believed that the incubation period for AIDS was one year, and at the maximum, two to three years (FDA, BPAC 1983b). A minority of persons proposed that AIDS was caused by a disease agent that had a much longer incubation period. In August 1982 Medical World News published a theory that AIDS was caused by a retrovirus; in 1982 Edgar Engleman, M.D., also proposed that AIDS was caused by a retrovirus (Engleman, Gallo interviews). The U.S. surveillance systems were ill-equipped to identify diseases with a long incubation period such as AIDS. Although 90 percent of AIDS cases were identified, it was difficult to identify those who were HIV infected but did not have AIDS (Francis interview).
The assumption by many decisionmakers that AIDS was similar to other viral agents in being caused by an agent with a short incubation period led to confusion regarding the incidence of AIDS in transfusion recipients or hemophiliacs, given the large number of blood units and blood products transfused annually (FDA, BPAC 1983b). At the time, there was insufficient information to state the mortality rate of AIDS; many believed it was approximately 40 percent or higher (FDA, BPAC 1983b). Decisionmakers did not know the high case fatality rate of AIDS and tended to deny the possibility of an infectious disease agent that could cause a devastating disease that would be fatal to most (if not all) of its victims. This information deficit, combined with incorrect assumptions regarding the natural history of AIDS, led to inaccurate analyses of targeted interventions for donor selection and donor blood testing. Thus, the known costs associated with donor screening interventions seemed to outweigh their benefits, which were unknown but depended on what were still incomplete scientific data.
If decisionmakers had known that AIDS had a long asymptomatic period during which people were infectious, they would have had to admit that the risk of AIDS transmission by transfusion was much higher than "one case per million patients transfused" (estimate of the American Association of Blood Banks, the American Red Cross, and the Council of Community Blood Centers, June 22, 1983; see Chapter 3). In addition, if they had known AIDS was virtually always fatal, decisionmakers might have been more aggressive about donor screening policies.
Lack of Leadership
The January 4, 1983, meeting in Atlanta was an opportunity for someone to take charge, but the meeting ended in disarray. The CDC had expected to leave the meeting with a consensus to draft recommendations to question donors, exclude all homosexuals, and implement surrogate testing (based on work done in their laboratories). The CDC had chosen Jeffrey Koplan, its assistant director for public health practice, to chair the meeting because he was believed to be a neutral figure in the AIDS effort (Curran, Evatt, Foege interviews). Whereas the CDC had hoped to pass the lead role over to FDA (Evatt interview), Dr. Bruce Evatt said he was stunned that the CDC "hit a brick wall" with the FDA. The CDC had been looking for overall agreement, but the crowded and raucous atmosphere made it impossible to achieve consensus (Curran, Evatt interviews).
The American Red Cross representative, Dr. Gerald Sandler, recalled that everyone at the meeting was "very frustrated" that the meeting did not reach a consensus on actions needed. He also noted that not one of Donald Francis' superiors had supported a recommendation to implement hepatitis B core testing. As a result, few in attendance accepted Francis' suggestions, as they assumed
he did not have the support of CDC Director William Foege (Sandler interview). The FDA's role in implementing surrogate testing was not clear, as the FDA representatives believed that more research was needed before the FDA could issue a recommendation (Parkman interview). The lack of good interagency communication was a problem, and some participants believed that someone should have established an interagency, national task force (Sandler interview).
After the meeting, the sentiment at CDC was one of frustration that they had failed to convince others that the evidence supported their hypothesis that the disease was transmitted through blood and blood products (Curran, Foege interviews). Several CDC scientists recall that it was difficult to convince others of the potential for blood-borne transmission and to motivate them to respond (Curran, Evatt interviews).
In his summary report of the meeting, Dr. Foege recommended that each Public Health Service agency provide candidate sets of recommendations for the prevention of AIDS in patients with hemophilia and for other recipients of blood and blood products to Dr. Koplan, assistant director for public health practice, CDC, and the three agencies (CDC, NIH, FDA) should then develop a uniform set of recommendations on AIDS. In addition, Dr. Foege expressed his belief that the meeting had been successful in presenting the most recent data on AIDS and had served as a "forum" for different views to be expressed (Foege 1983).
Blood banks, government agencies, and manufacturers were unable to reach a consensus on how extensively to screen for high-risk donors in order to substantially reduce the risk of HIV transmission through the blood supply. There was no consensus at the January 4, 1983, meeting, and it appears that no individual or organization took the lead to develop a consensus in the months that followed. Lack of agreement on the interpretation of scientific data, pressure by special interest groups, organizational inertia, and the unwillingness of the regulatory agencies to take a lead role in the crisis resulted in a delay of more than one year in implementing strategies to screen donors for risk factors associated with AIDS.
December 1983 Blood Products Advisory Committee Meeting
Interim Local Efforts to Screen Aggressively
In early to mid-1983, studies had shown that AIDS patients had a low ratio of CD4 lymphocytes to CD8 lymphocytes when compared with healthy
individuals (Evatt, Engleman interviews; Goedert 1989). On July 1, 1983, Stanford University Blood Bank became the first in the United States to screen donated blood with a surrogate test, which identified reversed T-cell ratios, to reduce transmission of AIDS. Between July 1983 and June 1985 at Stanford, a total of 33,831 blood donations were screened for CD4:CD8 ratios. Of those donations, 586 had CD4:CD8 ratios less than or equal to 0.85 and were discarded. However, serum samples from these donors were retained and later tested for HIV when the test became available. Dr. Edgar Engleman found that 1.9 percent of the 586 discarded donations were later found to be HIV positive (Galel, et al. 1995). The 1.9 percent of 586 donations translates to approximately 11 infected donations that were discarded. Each donation is usually divided into three components (red cells, platelets, and plasma), each of which is typically transfused into a different patient. Therefore, the removal of 11 infected units of blood may have protected 33 patients from acquiring HIV (Engleman interview; Galel, et al. 1995).
The test was relatively easy to implement at Stanford because the Stanford University Blood Bank was conducting immunological research at the time. Others interviewed stated that the CD4:CD8 ratio test would have been difficult to implement on a nationwide scale because the equipment required was costly and the test had to be performed manually (Perkins, Sandler, Osborn, Gompert interviews). It was believed that large-scale use of the CD4:CD8 ratio test required a flow cytometer, which was available only in research laboratory settings (Gompert interview).
In July 1983, NIH's National Heart, Lung, and Blood Institute released a request for application to develop tests to identify the AIDS carrier states and to measure the sensitivity of the tests. Shortly thereafter, Irwin Memorial Blood Bank in San Francisco, directed by Dr. Herbert Perkins, evaluated the anti-HBc test as a surrogate marker for HIV. The study took approximately three months, and the results were difficult to interpret, as the correlation between a positive anti-core test and selected areas of residence in San Francisco was more prominent by ethnic origin than sexual preference. Overall, 6 percent of donors tested positive for anti-HBc. The frequency of anti-HBc was higher in males than females, and the difference in frequency was larger between people of differing ethnic origins than between homosexuals and heterosexuals. The author concluded that implementing the test would not be of clear benefit and that the subsequent exclusion of 6 percent of donors could lead to blood shortages. In general, anti-core testing showed a 6 percent positive rate in blood donors, a 12 percent positive rate in blood donors who self-excluded, a 70 percent positive rate in gay men, and a 95 percent rate in AIDS patients in STD clinics (Pindyck interview). Irwin Memorial Blood Bank did implement the test in May 1984 to ease recipients' fears of receiving blood (Perkins interview).
Reliability of Surrogate Tests
On December 15-16, 1983, the FDA's Blood Products Advisory Committee (BPAC) held a two-day meeting to discuss the possible implementation of surrogate tests on blood donations to exclude high-risk donors. The objective of the BPAC meeting was to "review the results of research to define tests which could be applied to blood, plasma, or donors that would indicate an increased risk of the transmission of AIDS" (FDA, BPAC 1983).
Dr. Dennis Donohue, director of the FDA's Division of Blood and Blood Products, had recommended that hepatitis B anti-core testing be incorporated for routine plasma screening (in addition to current requirements) since it would identify 90 percent of all potentially infectious (or high-risk) donors (FDA, BPAC 1983c). In his opinion, the implementation of anti-core testing would add a further measure of confidence in product safety at a relatively low cost (Donohue interview; Ojala 1983). He stated, "Anti-core testing lends itself to the plasma situation," with only five to six central testing laboratories and one site responsible for product safety within each laboratory (CCBC 1983).
At the December BPAC meeting, industry representatives proposed the creation of a task force to deliberate the details of the recommendation and provide further information in three months (FDA, BPAC 1983c). According to CDC and FDA documents, industry proposed the task force in order to delay the implementation of surrogate testing (Donohue interview; Ojala 1983). An internal memorandum of one participant, Cutter Biological, stated that the proposal to convene a task force "was one that had been agreed upon by all the fractionators the previous evening" and that "the general thrust of the task force [was] to provide a delaying tactic for the implementation of further testing" (Ojala 1983). Although Dr. Donohue was not completely satisfied with the task force approach, he agreed to it; and thus the BPAC created an industry task force to consider the logistics of anti-HBc (core antibody) as an additional screening test.
Task Force Report on Surrogate Testing
The task force created at the December 15-16, 1983, BPAC meeting reported their findings on March 6, 1984. The members were divided as to "whether routine testing of potential blood and/or plasma donors for the presence of anti-HBc was an appropriate means of identifying members of high-risk groups associated with AIDS" (Rodell 1984). The report contained a majority position paper opposing the implementation of anti-HBc and a minority report favoring its implementation.
The task force reviewed several pilot tests performed at blood banks in high-risk areas. The pilot tests comprised four studies on anti-HBc; two studies
on B2-microglobulins; and one each on Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), immune complexes, Neopterin, T-cell ratio measurement, Thymosinal, and Alpha interferon. The discussion focused on the anti-HBc test.
Data showed that 5 percent to 18 percent of blood and plasma donors had a positive test for anti-core. The CDC data showed that 84 percent of homosexual males tested positive for anti-HBc and that 96 percent of IV drug users had a positive test for anti-core. The test itself was highly sensitive (98 percent) but not specific (70 percent).
The discussion at the December BPAC meeting had stipulated that ''cost-benefit analysis and disease prevalence must be considered in the decision regarding whether or not to use the test" (FDA, BPAC 1983c). However, the task force could not agree upon the true cost of the test, with estimates as low as $2.50 per test for plasma collectors and as high as $12.00 per donation for whole blood collections (Rodell 1984). Additional costs were the blood that would be discarded and the recruitment and replacement of donors. The task force could not agree on the costs and the benefits of using the anti-core test as a surrogate for high-risk donors.
A contemporaneous internal Cutter memorandum indicated that industry believed core testing would eventually become a requirement. At that time, Cutter executives recommended that the company implement core testing as quickly as possible to "obtain a competitive advantage in the market place" and that they "[make] no mention of [their] plans to others" (Ojala 1983).
Support for the Implementation of Anti-HBc. The minority who favored implementation of the anti-HBc test presented the following arguments: 60-80 percent of homosexuals tested positive for anti-HBc; the test would reduce the need for recall of blood products (i.e., AHF concentrate); the test could help reduce the incidence of non-A, non-B hepatitis in recipients of blood products; and blood and plasma collectors had an obligation to do all that was possible to increase the safety of the blood supply.
Opposition to Surrogate Testing. The majority against using the test believed that the anti-HBc test was insufficiently specific for AIDS and would exclude excessive numbers of donors. In addition, some speculated that there would be a reduction in the availability of donations from groups such as Mexican, African, and Asian Americans, who have a higher prevalence of core antibody but whose rare blood types are needed in the blood supply to service that very population. Finally, the high proportion of positive sera from known homosexuals suggested that the test was not distinguishing homosexuals with multiple partners who may have been carriers of AIDS from homosexuals who were not at increased risk of having AIDS (FDA, BPAC 1983c; CCBC 1983). They argued that wide-scale
implementation of core testing of donated blood would eliminate approximately 15 percent of plasma donors and 6–7 percent of whole blood donors (FDA, BPAC 1983c). Additional arguments were that the epidemic seemed somewhat contained within defined risk groups; the test would cause blood banks to incur high cost, and there would be a loss of the protective antibodies to hepatitis B in the blood supply.
Comment on the Blood Products Advisory Committee
The BPAC served in this instance as a forum through which the blood banks and plasma industry could, and did, influence the FDA to adopt policies that favored their interests at the expense of the public interest. The membership of BPAC included blood and plasma organization representatives, scientists, and physicians (FDA, BPAC 1983c). The group was not a monolith. Its members differed on the role of government agencies and actions to take regarding blood safety. There is also evidence from internal, nonpublic correspondence that some BPAC members deemphasized the risk to the blood supply in their public remarks but were very concerned in private. At a BPAC meeting in Washington in December 1982, Joseph Bove, M.D., committee chairman (and also chair of the American Association of Blood Bank's Committee on Transfusion Transmitted Diseases), said that there was not enough evidence that the blood supply could transmit AIDS to restrict donations from male homosexuals. However, in a contemporaneous report of the American Association of Blood Banks, Dr. Bove acknowledged the likelihood that AIDS was transmitted by blood. "I believe the most we can do is buy time," he stated, adding, "there is little doubt in my mind that additional transfusion-related cases and additional cases in patients with hemophilia will surface" (Bove 1983).
Informing the Public
The blood industry was concerned about providing information on AIDS to the public lest donors take fright and stop donating blood (Curran interview). In January 1983, Dr. Bove reported on behalf of the AABB's Committee on Transfusion Transmitted Diseases that "we do not want anything we do now to be interpreted by society (or by legal authorities) as agreeing with the concept—as yet unproven—that AIDS can be spread by blood" (Bove 1983).
Although many groups within the U.S. population had a stake in blood donations and blood transfusion, male homosexuals were well represented at the table where policymaking occurred, while other affected groups had minimal representation (e.g., patients with hemophilia were represented by the National Hemophilia Foundation) or no representation (e.g., future recipients of blood or blood products). The influence of special interest groups was reflected in the inconsistent recommendations about donor screening in the early 1980s. For example, as discussed earlier, prisoners could not donate blood even though their rate of hepatitis B infection was lower than the rate reported in male homosexuals. Haitians and tourists who had visited Haiti within the past three years could not donate (Katz 1983). There were no restrictions on donation, however, by the group with the highest prevalence of AIDS and hepatitis (homosexuals). Representatives of the homosexual groups demanded protection of gay rights to privacy or confidentiality. Moreover, there was a concern that homosexuals might lie about their sexual orientation and donate blood if blood banks implemented direct questions about sexual orientation (Evatt, Silvergleid interviews). Given the scientific uncertainties and lack of representation by other consumer groups, the demands of the gay groups exerted considerable force in the debates regarding donor screening (Rodell interview).
This review of the issues and central events concerning donor screening and deferral before the test for HIV (ELISA) became available in 1985 leads to several conclusions, the first of which follows:
When confronted with a range of options for using donor screening and deferral to reduce the probability of spreading HIV through the blood supply, blood bank officials and federal authorities consistently chose the least aggressive option that was justifiable.
In adopting this limited approach, responsible officials rejected options that may have slowed the spread of HIV to individuals with hemophilia and other recipients of blood and blood products. Among these options were asking male donors about sexual activity with other men and screening donated blood for the anti-HBc antibody. The Committee believes that both of these activities were reasonable to require in January 1983. The question is, given that these options were reasonable and justifiable, why did public health authorities reject them?
Having reviewed the available documentary evidence and having interviewed many of the key participants, the Committee believes that two of its three
hypotheses were powerful influences on decisionmaking about donor screening and deferral during 1983. The first hypothesis stated that lack of consensus about costs and benefits of screening and deferral resulted in decisions that took a limited approach to issues of donor safety. The second hypothesis stated that other constraints in the environment—which we categorize below as political, organizational, and historical—prevented decisionmakers from implementing screening for high-risk sexual practices and for anti-HBc. Though both of these hypotheses are supported by the facts, the first hypothesis explains rather different outcomes and events than the second. Their policy relevance differs widely as well.
There is little question that lack of consensus about the method of HIV transmission, the natural history of HIV-related disease, and the consequences of alternative modes of intervention to prevent its transmission was an important factor in decisionmaking on donor screening and deferral. There was, for example, uncertainty about the sensitivity and specificity of anti-HBc antibody screening as a method for identifying high-risk donors, and about the consequences of such screening for the safety of the blood supply. Some observers believed that the test was insensitive and would reduce the availability of naturally occurring antibody against hepatitis B infection. Others believed that the test was comparatively sensitive and that the benefits of its use would outweigh any possible costs. Lack of consensus also affected decisionmaking about using a history of homosexual encounters as a screening question. Though some observers, including most at the CDC, had concluded that HIV was spread in a manner analogous to hepatitis B (by exchange of bodily fluids, including blood), other reputable scientists continued to dispute this point of view or to argue that the probability of blood-borne transmission was very slight—a matter of one in a million, and therefore not a threat to those dependent on blood and blood products.
The absence of consensus on these basic matters of epidemiology led to second-order disagreements about the costs and benefits of alternative actions. These cost-benefit calculations were often hidden and unspoken. Indeed, the Committee suspects that many of those arguing alternative views would have been surprised and uncomfortable if told they were actually engaged in a dispute over cost-benefit calculations. However, as they projected the scenarios about what would happen if they undertook one strategy or another (e.g., the implementation of a screening test, the deferral of a high-risk group) and drew conclusions about the desirability of those scenarios, they were, in effect, tallying advantages and disadvantages of alternative courses of actions and reaching sums and totals that diverged from those advocating other approaches.
Uncertainty of this type is common in public decisionmaking, and it would be a mistake to relieve public health authorities of responsibility for their actions every time such legitimate disagreement occurred. When present, however, it has important implications for how decisions are made. Thus, when present, the forces postulated in the first hypothesis heighten the impact of the forces postulated in the second.
It is worth dwelling at some length on the nature and manifestations of environmental influences on decisions concerning donor screening and deferral, for the working of these influences reveals the clearest opportunity for improving decisionmaking with respect to the safety of the blood supply. The environmental forces working on the process of deciding about donor screening and deferral fit the following general categories: political, ideological, organizational, and historical.
The political circumstances influencing the outcome of decisions on HIV/AIDS took at least two general forms. First, interest group politics were at work in the efforts by homosexual groups to prevent the PHS from recognizing homosexuality as a risk factor in donor screening and deferral. The strong opposition of gay organizations undoubtedly had a major impact in heightening the sensitivity of FDA and CDC personnel to the potential negatives of taking a public health action—avoiding donation by men with a history of sex with other men—that would otherwise have made considerable sense. Interest group politics were also at work in the opposition of the blood products industry to screening for anti-HBc antibody. For the blood banks, and plasma fractionators, this was a matter of dollars and cents, and they used their access to FDA and to the BPAC to make their case.
Gay groups, plasma fractionators and blood banks had more freedom to make their self-interested cases because the scientific information that would have clarified the nature of the calamity facing the United States was still in dispute.
Political influences took a second form as well in this debate, expressed in the general lack of sensitivity that the executive branch of government showed toward HIV and AIDS during the 1980s. The precise reason for this insensitivity is unclear, but it is clear that the administration was generally reluctant during
the first half of the 1980s to treat AIDS as an urgent and serious public health threat. Thus, there was little potential political reward, and some political cost, associated with taking a leadership position in AIDS prevention, especially one that attracted political opposition from vocal and powerful groups that could argue that proposed actions were not required by scientific information.
An important ideological consideration at work during the period under review was a general antagonism or the part of the administration toward regulation. Even if AIDS had not been a topic of distaste for the Reagan administration, the issue of regulation itself made controlling the blood supply to prevent AIDS—in the absence of incontrovertible evidence of a public health crisis—an uphill battle.
The ideological position of the executive branch with respect to regulation put the burden of proof on agencies that wanted to take leadership in regulatory affairs.
This consideration occasions the Committee's fourth conclusion about donor screening and deferral.
Interagency squabbling, lack of coordination, and miscommunication are part of the bureaucratic landscape in any governmental setting whether one is talking of towns, cities, states, or national governments, in this country or abroad. Such forces were clearly at work in the case of decisionmaking with regard to donor screening and deferral during the period under review. The Committee concluded:
By far the most important organizational factor at work in explaining the cautious choices of public health authorities with regard to donor screening and deferral was mistrust and rivalry between the CDC and the FDA.
The Committee was particularly struck by comments made by FDA officials indicating a lack of confidence in the scientific capabilities of some of the CDC personnel. This lack of confidence seems to have reduced the credibility of CDC's early warnings and led FDA regulators, blood banks, and plasma fractionators to discount warnings presented at the January 4, 1983, meeting. The history of the CDC's handling of the swine flu episode less than a decade
earlier (during 1976–1977) might have colored FDA perceptions, but the startling fact remains that key personnel in the agency primarily responsible for preventing epidemic transmission through the blood supply (namely, the FDA) harbored significant doubts regarding the competence of the primary U.S. agency responsible for warning of the threat of such an epidemic. It is hard to imagine an instance in which such interagency disagreement could have contributed to a more unfortunate outcome.
The Committee drew another conclusion about organizational influences:
The structure and process of the FDA's Blood Products Advisory Committee (BPAC) lacked dimensions required to address nontechnical aspects of the controversy.
Because of the highly technical nature of many of its decisions, and the uncertainty that often accompanies them, the FDA has a history of relying on outside advisory groups to provide direction for many of its potentially controversial decisions. The area of blood policy and regulation was no exception. However, in this instance, the advisory system may have failed the FDA because the agency itself failed to understand the extent to which nontechnical issues, that is, issues of how to compare risks (such as the risk of HIV transmission versus the risk of further stigmatizing homosexuals), were actually at stake. The BPAC did not have the social, ethical, political, and economic expertise necessary to understand fully the ramifications of the decisions it was making. Furthermore, given how much authority FDA in effect has ceded to this advisory group, it did not sufficiently represent all potentially affected groups. In hindsight, such representation would have assured that all pertinent points of view would be considered during BPAC deliberations.
Throughout the Committee's review of events concerning donor screening and deferral in the early 1980s, we were struck by how one historical event influenced the way in which individuals and organizations conducted themselves and interpreted the evidence they were presented regarding the HIV epidemic. This episode, already mentioned above, was the federal government's experience with the swine flu epidemic. In early 1976, at the urging of officials of the CDC, the federal government, with the visible participation of President Ford, engaged in a crash program to immunize every American against a disease that never materialized. Millions were vaccinated, however, and some died of complications attributed to the vaccine (Neustadt and Fineberg 1978).
The swine flu episode seems simultaneously to have reduced the self-confidence of the agency and increased the skepticism with which its warnings have been regarded by other public health service groups.
It may be that CDC officials did not take a more forceful stand in urging their views out of fear of jeopardizing the CDC's remaining credibility. To what extent the lessons of the swine flu experience have positively influenced the behavior of the CDC, for example, by increasing the care with which it assesses the scientific evidence before issuing a warning of a new or threatening epidemic may never be known. However, the HIV case constitutes one clear example in which the experience and its lessons, however they were applied, led to disastrous results because of concern that being wrong on AIDS and the blood supply could destroy what remained of CDC's ability to see its warnings lead to public policy.
Although participants at the January 4, 1983, CDC meeting did not come to an agreement on actions regarding donor screening, there were several plasma fractionators and blood centers that initiated donor selection and screening interventions that surpassed the recommendations of the blood bank community and federal agencies. The decisionmakers could have defended wide-scale execution of these strategies in two ways: by obtaining information from a broader base of constituents, and by obtaining more information about possible consequences of action or nonaction from representatives of different theoretical premises regarding the epidemiology of AIDS. Instead, swine flu was used as a model by decisionmakers to illustrate the consequences of imprudent action. An important difference between swine flu and AIDS, however, was that swine flu was a threat that did not materialize, whereas AIDS cases were real, not theoretical, and were growing exponentially. Given the serious nature and devastating consequences of AIDS, all parties vested with the protection of the public health or the safety of the blood supply would have been justified in initiating both direct donor questioning and blood testing.
The Committee has not documented that any actions taken by decisionmakers were inconsistent with their responsibilities, but does believe that decisionmakers chose the least risky course (to them) throughout the events as they unfolded. A good example of this is that blood and plasma collection organizations failed to undertake anti-HBc testing and failed to recommend direct screening of homosexuals in 1983.
More stringent donor screening activities were not implemented in 1983 because of the limited scientific information related to AIDS and the influence of political, economic, and regulatory forces with different agendas. The lack of adequate scientific knowledge prevented the key actors from making an accurate (or reasonable) risk-benefit analysis of proposals to change the blood donor selection process. As a result of these uncertainties and pressures from the blood industry and special interest groups, options that would have reduced HIV
infection were not chosen, and policies that resulted in minimal change to the blood donor selection process were implemented. These policies not only provided a minimum of political risk to the blood banks and regulatory agencies in 1983, they also provided a minimum of protection from HIV for recipients of blood or blood products.
Donor Screening 1985–1995
With the implementation of HIV testing in 1985, the extent of the problem of the HIV infectious agent in the blood supply was quickly understood. The perception of the safety of the blood supply changed both in the public's view and among the blood bank professionals. The era of HIV shifted the field of blood banking from one dominated by serology to one in which infectious disease transmission, donor concerns, and the quest for total safety have become paramount (Bove 1990). Several changes were introduced concerning donor screening, mainly the introduction of new laboratory tests.
Since 1985, donor screening has involved "lookback." Lookback is the tracing of a blood donor found to have anti-HIV (and who had donated in the past), to all recipients of the previous donation(s), who in turn are tested for HIV. Donor deferral lists have been used in the blood banks since the 1970s regarding donors positive for hepatitis B surface antigen (HBsAg), as well as donors linked with post-transfusion hepatitis. These lists have been extended to include donors found to be HIV positive and donors positive for other disease markers. Every donation is checked for previous donation by that donor to see if any unit from the donor has been rejected in the past.
The measures taken up to 1985 are still in effect: avoiding high-risk individuals, questions regarding HIV-associated symptoms, and confidential self-exclusion. Questions regarding foreign travel have been added in order to defer donors visiting areas endemic for malaria or those visiting central Africa, which has a high HIV prevalence. Questions regarding previous treatment with growth hormone have been added to defer previously treated donors because of the fear of transmission of Creutzfeldt-Jakob disease.
Additional screening tests for donated blood have been considered and were added after 1985, both for HIV and for hepatitis.
The anti-HIV test implemented in 1985 (ELISA) became more sensitive and specific following the first available kits. In spite of the improvement, a few
post-transfusion HIV infections from donations in the "window" period (the time period between infection with the virus, but prior to a detectable antibody response in blood or plasma) continued to occur. In order to evaluate the effect of adding the p24 antigen test (a viral antigen that can be present in the window period), 500,000 donors in 10 different areas in the United States were tested for p24 (Alter, et al. 1990). As no cases of p24 positive blood donors were found, the test was not implemented on a wide-scale basis.
HIV-2 is a retrovirus that is distantly related to HIV-1 (HIV) that also causes AIDS in humans. Although it is prevalent in areas of West Africa and other parts of the world, it is only very rarely found in the United States. Despite its rarity in the United States, the FDA required that all blood donations be screened for HIV-2 in April 1992. A new variant, known as HIV subtype 0, has also been described and may also be included in the routine screening in the future.
Post-transfusion non-A, non-B hepatitis cases continued to be reported. Without any evidence that the causative agent would soon be elucidated, surrogate tests were suggested. Based on previous studies and new evidence, the surrogate testing for non-A, non-B hepatitis was instituted during 1986–1987 by using both the ALT and Anti-HBc tests. In 1989, the genomic structure of a putative NANB virus (Hepatitis C virus [HCV]) was discovered. As a result, a test for antibodies to the HCV virus was licensed and implemented as a screening test for HCV in 1990.
In an NIH consensus conference held in January 1995 (there was no other consensus conference held earlier by the NIH), it was recommended that the ALT surrogate test be discontinued. However, anti-HBc was retained, not as a non-A, non-B surrogate marker, but as a second hepatitis B screening test for cases with low HBsAg titer.
HTLV-I and HTLV-II
In 1988 six positive HTLV-I cases were reported among 40,000 donors (Williams, et al. 1988). In November 1988, a screening test for HTLV-I (virus that causes leukemia and myelopathy) was instituted for all blood units. HTLV-I has been found in the United States, but HTLV-II has been seen more frequently. Not all blood donors with HTLV-II infection are effectively identified using the HTLV-I antibody tests; instances of transmission of HTLV-II by blood screened negative for HTLV-I have been reported.
Current Donor Screening Procedures
Currently, donor screening provides a potential donor with four opportunities to self-defer. Prior to donating blood, each donor is asked to read an introductory pamphlet about donating blood and about infections transmitted by blood, especially HIV. Those who think they are at risk are asked not to donate. This is the first opportunity to self-defer. A trained health professional then conducts a confidential interview with each donor, taking a health history and asking direct questions about high-risk behaviors, including drug use, sexual relations with drug users, and, for men, if they have had sexual relations with another man since 1977. Answering yes to one or more of these questions results in a temporary or indefinite deferral, in accordance with FDA recommendations and requirements. At this time the donor is asked to sign a release statement confirming that he or she has no risk for infection with HIV. This is the second opportunity to self-defer.
Donors are tested for anemia and checked for physical signs of intravenous drug use. Donors receive a ''confidential unit exclusion" form and a call-back card. High-risk donors who may not wish to publicly acknowledge their risk behaviors may confidentially exclude their unit of blood by peeling a bar code sticker off the unit exclusion form and placing it on their donation record. A computer reads the bar code as "transfuse" or "do not transfuse" depending upon which sticker is used. This is the third opportunity to self-defer. The call-back card gives donors a telephone number to call within 24 hours and a special identification code to use if for any reason after leaving the donation site they decide their blood should not be used. This is the fourth opportunity to self-defer.
Any unit of blood found positive for any of the tests is destroyed and the donor is permanently deferred by being placed in a computer database (American Red Cross Blood Services 1994).
Current Infectious Risk Through Blood Transfusion
The current estimated risk (Dodd 1992, 1994; Busch, et al. 1995; Lackritz, et al. 1995) of becoming infected by the viruses being tested for is:
HCV (hepatitis C)
1:2,000 to 1:6,000
HBV (hepatitis B)
HTLV (leukemia and myelopathy)
1:50,000 to 1:70,000
Other infectious agents that are possible hazards are an additional hepatitis agent (non A,B,C), Chagas disease, Creutzfeldt-Jakob disease, Babbeiosis, new
zoonotic infections, and new unknown agents. The problems associated with bacterial infection in blood units and especially in platelet concentrates have also not been completely resolved. Other issues concerning the safety of blood transfusion involve the long-term effects of lymphocytes transfused along with red blood cells, as well as with platelet transfusions.
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