5
Donor Screening and Deferral

INTRODUCTION

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



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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 5 Donor Screening and Deferral INTRODUCTION 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Critical Events 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.

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Explanatory Hypotheses 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 Hepatitis 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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). Donor Pools 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,

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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:

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Hypothesis Two 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. Political Factors 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Ideological Factors 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. Organizational Factors 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Historical Factors 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).

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. AFTERWORD 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. HIV 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. Hepatitis 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.

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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: HIV (AIDS) 1:420,000 HCV (hepatitis C) 1:2,000 to 1:6,000 HBV (hepatitis B) 1:200,000 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

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking 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. REFERENCES Allen, J. Garrott, et al. Blood Transfusion and Serum Hepatitis. Annals of Surgery, vol. 150; 1959. Alpha Therapeutics. Statement submitted to Institute of Medicine; September 9, 1994. Alter, Harvey, et al. Prevalence of HIV Type 1 p24 Antigen in U.S. Blood Donors—An Assessment of the Efficacy of Testing in Donor Screening. New England Journal of Medicine, vol. 323; 1990. American Association of Blood Banks, American Red Cross and Council of Community Blood Centers. Joint Statement on AIDS Related to Transfusion. January 13, 1983. American Association of Blood Banks. Standards for Blood Banks and Transfusion Services, Tenth Edition, Washington, D.C.; 1982. American Blood Resources Association, Recommendations on AIDS and Plasma Donor Deferral. January 28, 1983. American Red Cross Blood Services, Documents submitted to the Institute of Medicine; September 1, 1994. Bensen, Paul B. Jaundice Occurring One to Four Months After Transfusion of Blood or Plasma. Journal of the American Medical Association, vol. 121: 1943. Bove, Joseph, Chairman, Committee on Transfusion Transmitted Disease. Report to the Board, American Association of Blood Banks; January 24, 1983. Bove, Joseph. Testing in the Years Ahead. Transfusion, Vol. 30; 1990. Busch, Risk of Human Immunodeficiency Virus transmission by blood transfusions before the implementation of HIV-1 anti-body screening. Transfusion; 1991. Busch, et al. Paper presented at the NIH Consensus Development Conference; January 1995. Centers for Disease Control, Morbidity and Mortality Weekly Report , July 16, 1982 Centers for Disease Control, Morbidity and Mortality Weekly Report , December 10, 1982 Centers for Disease Control, Morbidity and Mortality Weekly Report , Prevention of Acquired Immune Deficiency Syndrome (AIDS): Report of Inter-Agency Recommendations; March 4, 1983. Council of Community Blood Centers. Blood Products Advisory Committee Recommends Fractionators Use Anti-core Screening Test. Council of Community Blood Centers Newsletter; December 23, 1983. Council of Community Blood Centers. Submission to the Institute of Medicine; 1994. Cumming, American Red Cross. Memorandum to Mr. de Beaufort, American Red Cross National Headquarters; February 5, 1983. Dodd, Roger, American Red Cross. Memorandum to Katz, Executive Director, Blood Services; July 9, 1982.

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking Dodd, Roger. "Adverse Consequences of Blood Transfusion: Quantitative Risk Estimates." in Blood Supply: Risks, Perceptions, and Prospects for the Future. American Association of Blood Banks; 1994. Dodd, Roger. The Risk of Transfusion-Transmitted Infections. New England Journal of Medicine, vol. 327; 1992. Doll, et al. Human Immunodeficiency Virus type 1 Infected Blood Donors: Behavioral Characteristics and Reasons for Donation. Transfusion; May 1991. Eckert, R. AIDS and the Blood Bankers. Regulation; September 1986. Food and Drug Administration. Blood Products Advisory Committee, July 19, 1983a. Food and Drug Administration. Blood Products Advisory Committee, February 7, 1983b. Food and Drug Administration. Blood Products Advisory Committee, December 15–16, 1983c. Foege, William. Summary Report of Workgroup to Identify Opportunities for Prevention of Acquired Immune Deficiency Syndrome (AIDS); January 4, 1983. Francis, Donald, CDC. Memorandum to Koplan, Jeffrey; January 6, 1983. Galel, et al. Prevention of AIDS Transmission Through Screening of the Blood Supply. Annual Reviews of Immunology, Vol. 13; 1995. Goedert, A Prospective Study of HIV Type 1 Infections and the Development of AIDS in Subjects with Hemophilia. New England Journal of Medicine , 1989. Katz, American Red Cross. Information to Blood Service Regions, BSL 83-12; January 26, 1983. Lackritz, et al. Paper presented at NIH Consensus Development Conference; January 1995. McDougal, J.S., Martin, L.W., Cort, S.P., Mozen, M., Heldebrant, C.M., Evatt, B.L., "Thermal Inactivation of the Acquired Immunodeficiency Syndrome Virus, Human T Lymphotropic Virus-III/Lymphadenopathy-associated Virus, with Special Reference to Antihemophilic Factor," The Journal of Clinical Investigation, Vol. 76; August 1985. National Hemophilia Foundation. Recommendations to Prevent AIDS in Patients with Hemophilia. January 14, 1983. Neustadt, R. and Fineberg, H. The Swine Flu Affair: Decisionmaking on a Slippery Disease. U.S. Department of Health, Education, and Welfare; 1978 Ojala, S., Cutter. Memorandum to those listed; December 19, 1983. Office of Technology Assessment. Blood Policy and Technology. U.S. Government Printing Office, Washington, D.C.; January 1985. Petricciani, John, M.D., Food and Drug Administration, Office of Biologics. Letter to All establishments collecting human blood for transfusion. March 21, 1983a. Petricciani, John, M.D., Food and Drug Administration, Office of Biologics. Letter to All establishments collecting source plasma. March 24, 1983b. Petricciani, John, M.D. Food and Drug Administration, Office of Biologics. Letter to All licensed manufacturers of plasma derivatives. March 24, 1983c. Pindyck J, et al. Measures to Decrease the Risk of Acquired Immune Deficiency Transmission by Blood Transfusion. Evidence of Volunteer Blood Donor Cooperation. Transfusion, vol. 25; 1985. Rodell, Michael. Hepatitis B Core Antibody Testing Study Group. Plasma Quarterly; Fall 1984.

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HIV and the Blood Supply: An Analysis of Crisis Decisionmaking Seeff, Leonard. Transfusion Associated Hepatitis: Past and Present. Transfusion Medicine Reviews; December 1988. U.S. Comptroller General. Report to the Congress, Problems Carrying Out the National Blood Policy; 1975. Williams, Alan E., et al. Seroprevalence and Epidemiological Correlates of HTLV-1 Infection in U.S. Blood Donors. Science, vol. 240; 1988.

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