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Institute of Medicine (US) Committee to Study HIV Transmission Through Blood and Blood Products; Leveton LB, Sox HC Jr., Stoto MA, editors. HIV And The Blood Supply: An Analysis Of Crisis Decisionmaking. Washington (DC): National Academies Press (US); 1995.

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HIV And The Blood Supply: An Analysis Of Crisis Decisionmaking.

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7Risk Communication to Physicians and Patients

Introduction

The introduction of HIV into the blood supply posed powerful dangers to those individuals with hemophilia and recipients of blood transfusions during the early years of the epidemic. During the period from 1982 to 1984, before the AIDS virus was finally identified and a test developed to determine its presence, there was considerable speculation about whether the blood supply could be a vector for this new, fatal infection. As evidence about risk developed, consumers of blood and blood products—as well as their physicians—found themselves in a complex dilemma. Continued use of blood and blood products might heighten the risk of acquiring a new disease. Reducing or discouraging the use of blood products might increase the morbidity and mortality associated with hemophilia. Approximately half of the 16,000 hemophiliacs and over 12,000 recipients of blood transfusions became infected with HIV during this period (CDC, MMWR, July 23, 1993). More effective communication of the risks associated with blood and blood products and the opportunity to choose from a wide spectrum of clinical options might have averted some of these infections.

To explore these questions, the Committee analyzed how the risks associated with using blood and blood products as well as clinical options were communicated to relevant physicians and patients by examining the content and process of the communications from 1982 through 1985. The Committee focused on the information available to decisionmakers and analyzed the institutional, social, and cultural obstacles to effective risk communication. The analysis includes an examination of the information about the risks associated with blood and blood products and possible risk reduction options that were available during this period of uncertainty. The chapter also considers the role of a voluntary health organization, the National Hemophilia Foundation (NHF), in the communication of information to physicians and individuals with hemophilia.

Framework For Analysis

Critical Questions

The Committee addressed four fundamental questions about the content and process of risk communication:

1.

What clinical options for risk reduction, even if marginally effective, were available and could have been communicated?

2.

What information was actually communicated to patients?

3.

What were the institutional obstacles to risk communication?

4.

What were the social and cultural obstacles that influenced physician-patient relationships and risk communication?

To better understand how information about the risks associated with blood and blood products was actually perceived and responded to at the clinical level, the Committee utilized a case study approach. This approach provided the means for the Committee to gain an in-depth familiarization with the context and culture of hemophilia treatment. It also helped illuminate the range of possible clinical options that existed during this period of uncertainty, and to assess their impact in these instances. Finally, the Committee evaluated the institutional, social, and cultural obstacles to communication about the risk of using blood and blood products.

Critical Factors

Three critical factors in the environment for individuals who are dependent on blood products help explain risk communication patterns: (1) progress in the treatment of hemophilia; (2) the development of a national network of hemophilia treatment centers; and (3) the medical community's consideration of hepatitis as an ''acceptable risk." These factors shaped the decisionmaking process as the AIDS epidemic emerged.

The advent of antihemophilic factor (AHF) concentrate in the early 1970s brought a remarkably effective means to treat a disease characterized by spontaneous bleeding, pain, crippling, and early death (Jones and Ratnoff 1991). AHF concentrates significantly altered the morbidity and mortality associated with hemophilia, dramatically improving the quality of life of those affected. In 1972, the major cause of death for individuals with hemophilia was cerebral hemorrhage. The mean life expectancy was approximately 40 years between 1941 and 1960 and approximately 54 years between 1961 and 1970; it increased to 60 years between 1971 and 1980 (Jones and Ratnoff 1991). By the early 1980s, hemorrhage was no longer the major cause of death (Levine interview). To the extent that the pain and the visible signs of a crippling disease were reduced, the stigma of hemophilia was also significantly reduced (Jones and Ratnoff 1991; Resnik 1994).

While the development of the AHF concentrate products revolutionized the treatment of hemophilia, the development of hemophilia treatment centers provided a nationwide system of care and treatment. In 1975, the federal government established funding for 20 regional centers, representing approximately 100 local treatment centers, to provide hemophilia care (Department of Health and Human Services 1994). The treatment centers ensured comprehensive medical care and early application of treatment as well as fostering a sense of community for individuals with hemophilia and their families (Smith and Levine 1984).

In the setting of the treatment center both physicians and patients were able to see the advantages of treating bleeding episodes early. This observation translated into advocating home care therapy; hemophiliac patients and their families quickly became proficient in self-infusion (Smith and Levine 1984). The results were significant—home care therapy nearly eliminated the crippling associated with the disease and led to significant improvements in the health and quality of life for the individual with hemophilia (Eyster, et al. 1980; Brinkhous 1981; Smith and Levine 1984; Rosendaal, et al. 1991; Chorba, et al. 1994).

In this context of progress in the treatment and care of hemophilia, the physicians treating hemophilia and their patients shared in a rather unique and close relationship. In part, this stemmed from the somewhat insular care network for individuals with hemophilia at the hemophilia treatment centers, and in part, it developed from sharing in the significant medical progress in hemophilia treatment. Hemophiliac patients and their families generally held their physicians in high regard and trusted them implicitly (Kasper interview). The third important factor in the treatment of the hemophilia patient in the years before the AIDS epidemic was the recognition that infection with hepatitis B as well as non-A, non-B hepatitis was a frequent risk associated with use of AHF concentrates (Aronson 1979; Johnson et al. 1985; Chorba et al. 1994; Hoyer 1994; Goldfinger, Kasper, Louvrein, Roberts interviews). This observation can be traced to the early 1970s when hepatitis emerged as a frequent complication in patients receiving blood and blood products (Seeff 1988). During this era, it came to be expected that most hemophiliac patients would develop hepatitis (Chorba, et al. 1994; Hoyer interview). Although hepatitis infections were occasionally severe, leading to liver failure and death (Aronson 1979; Johnson, et al. 1985), the benefits of treatment seemed to outweigh the risks from such infections (Hoyer interview). In the context of the dramatic improvements in the care and treatment of hemophilia offered by AHF concentrates, infection associated with the use of these blood products came to be deemed an "acceptable risk" (Aledort 1982; Aronson 1979; Hoyer 1994; Furie, Roberts interviews).

It was against this background that the initial reports began to surface that individuals with hemophilia and transfusion recipients might be at risk for a new disease, called AIDS. There was considerable uncertainty and disagreement among medical, scientific, and public health decisionmakers about whether AIDS was a new disease, and if it could be transmitted via a blood-borne agent (Public Health Service 1982; FDA, BPAC 1983). If AIDS was a new, blood-borne disease, the implications for individuals with hemophilia—as well as other consumers of blood and blood products—could be dire.

The Role of the National Hemophilia Foundation

In the early 1980s, there was no organization that assumed specific responsibility for communicating directly with physicians and patients about the risks associated with blood and blood products. Although the hemophilia treatment centers received federal funding, the basis of information about the nature of the risk of AIDS associated with blood and blood products came from the National Hemophilia Foundation (NHF) and its Medical and Scientific Advisory Council (MASAC), whose membership included medical directors of hemophilia treatment centers. Immediately upon hearing directly from the CDC about three cases of AIDS in individuals with hemophilia (CDC, MMWR, July 1982), the NHF took on the responsibility of communicating to physicians and patients about the epidemic and the risks associated with use of blood products. In this role, NHF served a crucial function as an intermediary between the sources of scientific and medical information (i.e., CDC, FDA, plasma fractionation industry) and the consumers of that information—the physicians and users of blood products who had to make daily decisions about hemophilia treatment.

Founded in 1948, the NHF was committed to advancing the care and treatment of persons with hemophilia and strengthening the community. During the mid-1970s, NHF helped to successfully lobby for major changes in the care and treatment of hemophilia (Aledort, McPherson interviews; Brownstein 1994). But in 1982, it stepped into a new role for which it had little preparation and experience and limited resources. First, in the early 1980s, the NHF was recovering from bankruptcy and had a small staff (Brownstein 1994; Bias, Carman interviews). In addition, it had limited funding and expertise for developing a system for communicating information until it obtained additional support from Human Resources and Services Administration's Office of Maternal and Child Health (HRSA/OMCH) in October 1983 (NHF 1983). The decisions about what to communicate and the process for communication, however, remained the primary responsibility of the NHF.

The leadership of NHF was comprised of individuals who were committed to the advancement of medical care and services for individuals with hemophilia. The NHF had established close relationships with the plasma fractionation industry (pharmaceutical companies) which provided badly needed financial support for some of the NHF's activities, including its communication programs (Aledort interview; Hammes pers. com. 1995; Brownstein, 1994). NHF, with the help of its newly reconstituted Medical and Scientific Advisory Council (MASAC), established itself as the primary source of information for the consumers of blood products (Brownstein 1994). Given the heated tenor of the discussions of the AIDS crisis, and the complex scientific, medical, and social questions that it would raise, the NHF's assumption of responsibility for communicating expert advice was without precedent in its history.

The NHF utilized two modes of communication, medical bulletins and chapter advisories, for educating and advising physicians and patients concerning what was and was not known at the time. (Appendix C summarizes these communications.) Medical bulletins formulated by members of the NHF AIDS Task Force and some of the members from MASAC (referred to as Hemophilia Newsnotes) were sent directly to treating physicians (primarily at the hemophilia treatment centers); chapter advisories were sent to the local chapters of the NHF. From July 1982 through December 1985, the NHF issued 32 medical bulletins and 37 chapter advisories. Both forms of communication came from the leadership of the NHF rather than directly from MASAC (Aledort, Carman interviews).

The information developed for the recommendations came from the interactions of the NHF AIDS Task Force with government and private organizations. The communications were written by the members of the NHF AIDS Task Force, with review and approval of MASAC members. The AIDS Task Force was an ad hoc group comprised of the MASAC chair (Dr. Leon Hoyer), the NHF officers including the executive director (Mr. Alan Brownstein), the medical director (Dr. Louis Aledort), and the president (Dr. Charles Carman). The NHF AIDS Task Force had the primary role of collecting information, interacting with the various federal and private organizations about the risks associated with blood products, and developing recommendations and advising the NHF leadership about the HIV risks. The NHF executive director and board had the final authority over the AIDS Task Force and MASAC recommendations (Aledort, Carman interviews). The process of developing recommendations and providing information also included a review by CDC scientist Bruce Evatt to ensure accuracy (Aledort, Carman, Evatt interviews).

The October 22, 1983, meeting of MASAC was the occasion to learn that the Office of Maternal and Child Health (OMCH), the source of federal funding for the hemophilia treatment centers, would provide practical support for the establishment of a hemophilia information exchange network. Dr. Jeanne Lusher, a member of MASAC, was designated to be the project director for the hemophilia information exchange (HIE) (NHF 1982a). OMCH worked with MASAC and the NHF to set up a process for information exchange. The NHF, however, took the primary responsibility for developing the information and disseminating it to the treatment centers and chapters (McPherson interview). The purpose of the information exchange network was to provide paid subscribers with "preprints" (manuscripts not yet published in scientific journals) concerning various aspects of hemophilia, including, orthopedic management, genetic analysis, inhibitors, and infectious complications such as AIDS. A bibliography of articles of interest to the hemophilia community was included in each distribution.

Although MASAC had committed itself in October 1982 to provide the same information to patients that was provided to physicians, the primary recipients of NHF communications were the physicians and chapter leaders (NHF 1982b). Indeed, a cover letter, dated July 19, 1982, from Charles Carman to NHF chapter presidents, accompanying Chapter Advisory #2, explicitly recommended that the Advisory be kept in the chapter files to answer questions about Pneumocystis carinii pneumonia (PCP) and that mass mailings were not necessary.

Although some specific messages changed over time, the recommendation to continue to use AHF concentrate for severe hemophiliacs remained constant from January 1983 to October 1984, when the NHF first recommended using heat-treated concentrates. The communication issued on July 14, 1982 (Patient Alert No. 1), was the first of many NHF communications that stressed that "the CDC was not advising a change in treatment regimen at this time." Although some specific recommendations changed over time, one message remained constant throughout the entire period: "Patients [should] maintain the use of concentrate or cryoprecipitate as prescribed by their physicians. The life and health of hemophiliacs depends on the appropriate use of blood products." The NHF reaffirmed this message in medical bulletins and chapter advisories on many occasions, six of which, between May 11, 1983, and October 5, 1984, were within days of recalls (i.e., industry's voluntary withdrawal) of AHF concentrate due to the diagnosis of AIDS in individuals donors. Many of the communications contained messages to encourage patients to maintain current treatments and to reassure them that the risk was remote despite the possibility that the patients may be using vials of AHF concentrate from lots recalled by industry's voluntary withdrawal of the product [Medical Bulletin #7, May 1983; Chapter Advisory #8, May 1983; Chapter Advisory #9, September 1983; Chapter Advisory #11, November 1983; Chapter Advisory #13, January 1984; Chapter Advisory #19, October 1984; Chapter Advisory #24, December 1984; Medical Bulletin #20, December 1984].

Risk Reduction Options

Many of the debates and discussions that occurred during the MASAC and NHF meetings concerned clinical options to reduce the risk of AIDS transmission for individuals who were using blood products or were in need of receiving blood transfusion. Although these options to reduce the risk of AIDS transmission through blood products were not appropriate to every patient's circumstances, there was a range of clinical approaches for physicians and their patients to consider. The full list of these options is shown in Table 7.1. The Committee found that, for the most part, there was little systematic communication and assessment of the full range of these options for reducing the risk of infection.

Table 7.1. Summary of Clinical Options, Status and Sources of Recommendations,.

Table 7.1

Summary of Clinical Options, Status and Sources of Recommendations,.

Specific Options

The primary clinical option for mild, moderate, and previously untreated hemophiliacs was to use cryoprecipitate rather than AHF concentrate. Because cryoprecipitate is derived from single donors or small pools of 10–15 donors, some physicians believed that it was less likely to be infected with AIDS (Roberts interview; Ratnoff 1994). There were several rationales for not recommending cryoprecipitate, including issues of adequate supply, requirements for storage, and unfavorable attitudes (Aledort, Dietrich, Kasper, Levine, Lusher interviews). In addition, blood bank officials were concerned about the burden of extra work for the blood banks (Barker, Sandler interviews). A minority of MASAC members advocated cryoprecipitate for treating mild, moderate, and severe hemophilia, but it was never an official recommendation of MASAC or the NHF. The Committee is not aware of any systematic studies of cryoprecipitate, and it seems that this option was discarded as infeasible without a thorough analysis.

The NHF communications reflected inconsistency, or at least some degree of ambivalence, in the presentation of information about this option. Communications as early as December 21, 1982, and again on January 14, 1983, cautioned against introduction of AHF concentrates to individuals who had never used them before and recommended the use of cryoprecipitate instead [Chapter Advisory #5 and Medical Bulletin #4, December 1982]. Chapter Advisory #12 (December 21, 1983) said that the potential advantages of cryoprecipitate over AHF concentrates were unknown. Most of the adult hemophiliacs had used cryoprecipitate or fresh frozen plasma to treat their disease before AHF concentrate became the standard treatment in the mid- to late 1970s. It is more difficult to treat adults who have severe hemophilia with the cryoprecipitate or fresh frozen plasma because of the large amount that is required. To go back to cryoprecipitate or fresh frozen plasma presented several obstacles in terms of logistics, amount needed, and the time involved in this type of infusion.

That the NHF and MASAC did not recommend some clinical options to prevent AIDS in hemophiliac patients did not discourage some patients and their physicians from improvising. The Committee found several instances of physicians implementing risk-reduction strategies such as discouraging prophylactic treatment and reevaluating the frequency of using AHF concentrate. Physicians who implemented these options instructed their patients about what types of bleeds to treat, when, and how often. Personal circumstances and fears about not treating serious bleeds made some physicians apprehensive about instructing patients to not treat bleeding episodes (Aledort, Dietrich, Levine interviews).

The NHF recommended the use of DDAVP (desmopressin acetate) to treat mild and moderate cases of hemophilia A, an option implemented by several physicians, initially for mild cases and later for moderate individuals (Dietrich, Kasper interviews). The availability of this experimental product came at the urging of the medical community, both to plasma fractionators for development and to FDA expeditious licensing of the product, which occurred by April 1984 [Medical Bulletin #5, January 1983; Chapter Advisory #15, April 1984].

In many cases, physicians treating individuals with hemophilia decided to delay elective surgical procedures on their patients (Dietrich, Kasper interviews), only to abandon this strategy after none of their patients developed symptoms of AIDS and individual patients insisted upon having the corrective surgery without delay (Dietrich interview; see also Case Study Two below).

Neither the NHF and MASAC nor individual physicians appear to have devoted much effort to communicating the possibility of the risk of secondary transmission of HIV to their sexually active, and possibly HIV-infected, hemophilia patients. The NHF did not communicate information about the risk of secondary transmission until it issued Chapter Advisory #14 on February 3, 1984. The communication discussed the risk of secondary transmission through sexual activity or other forms of intimate contact, but characterized the risk as remote. The NHF bulletin encouraged open communication between patients and physicians (NHF 1984). The MASAC never issued official recommendations about sexual transmission of AIDS.

The February 4, 1984, NHF medical bulletin communication about secondary transmission of AIDS provided information on the death of a 70-year-old hemophiliac who had died from AIDS in May 1983. The NHF communication stated that the wife was not known to be a member of a high-risk group, but it was still possible that she developed AIDS first and spread it to her husband, and that the patient's vulnerability may have been a function of age, rather than sexual contact. The communication stated there was still controversy about whether secondary transmission of AIDS could occur but that all agreed that if sexual partners of hemophiliacs were at increased risk of contracting AIDS, the risk was small: "Individual patients and their treaters need to consider whether or not they wish to employ prophylactic methods (e.g., condoms) in continuing their sexual relations as a strictly precautionary and temporary measure until more is learned about AIDS." The Committee learned that some physicians were frightened by the possibility of secondary transmission of AIDS (Hoyer interview). MASAC acknowledged its limitations in dealing with AIDS transmission. According to Brownstein (1994), MASAC members were hematologists and did not have expertise in the area of sexual disease transmission. The NHF transmitted information about sexual transmission of AIDS from the CDC to treating physicians as they were informed.

The NHF did not always fully communicate information. The NHF and MASAC did not communicate information about the availability of heat-treated products until October 1984, when it recommended using them after all four companies had received FDA license approval for their heat-treated products. The rationale for not prescribing heat-treated products included the absence of clinical trials to prove their effectiveness for viral inactivation, a belief that use of these products could lead to the development of inhibitors, their higher costs to the patient, and that these products were developed for eliminating hepatitis and therefore not necessary for those who were known to be infected with hepatitis (Aledort, Dietrich, Lusher interviews) (see Chapters 4 and 6). The NHF communications did not include information to help patients better understand product treatment methods, such as heat treatment, and other possible risk-reduction options.

The Process for Developing NHF Guidelines

After reviewing specific clinical options, the Committee examined the process by which the NHF developed its recommendations. While information about potential consequences for large-scale infection within the hemophilia community alerted members of the NHF to recommend several alternative treatment options, the NHF did not provide full information about potential risk reduction options. The NHF also did not say that there were debates within MASAC regarding some of the potential treatment options (Carman, Roberts interviews). Although the evidence that AIDS could be blood-borne was not conclusive in the earliest stages of the epidemic, the sense of urgency with which meetings were called and conducted, the early discussions of the potential needs for increased production of cryoprecipitate, and the explicit consideration of other possible changes in the treatment and management of hemophilia provide evidence that the NHF leadership was aware of a range of clinical alternatives and their implications for individual risk reduction (Carman, Levine interviews; NHF 1982a,b, 1983).

The initial discussions between the NHF leadership and experts from CDC, FDA, and PHS, and industry about the report of three immune-suppressed hemophiliacs resulted in immediate concern and specific recommendations [Medical Bulletin #4 and Chapter Advisory #5, December 1982] from the NHF to the commercial and voluntary blood community (NHF 1982a,b). These recommendations included implementing donor screening and testing measures as well as expediting efforts in viral inactivation methods. Even as early as November 2, 1982, an NHF letter to manufacturers of AHF concentrate urged the exclusion of high-risk donors of plasma (Carman and Aledort, 1982). The timing, range, and advocacy of these recommendations on behalf of instituting these risk-reducing changes in the blood industry is evidence that NHF officials had access to information and did appreciate and take seriously the warnings from the CDC. The MASAC was well aware of the alternative approaches to treatment as early as January 1983 and in some instances made recommendations for their use. On January 14, 1983, MASAC officially recommended a range of clinical options for reducing the risk of HIV exposure for mild or moderate hemophiliacs and previously untreated cases.

As indicated in Appendix C, the communication strategy of the NHF did reveal incremental modification of several recommendations as new information became available (e.g., avoiding sexual contact, considering heat treatment), but provided it relatively late and did not provide physicians with further information on how to switch severe hemophiliac patients to cryoprecipitate.

When plasma fractionators began to withdraw suspected lots of AHF concentrate found to be associated with a donor known to have or suspected of having AIDS (see Chapter 6), physicians had to intensify their efforts to communicate the risks associated with blood and blood products to patients and to notify patients who may have been using, or have in their possession, contaminated lots of AHF concentrate. Dr. Jenne Lusher stated, ''It made it much more apparent to our patients; even if they were not involved in the recall, a particular recall, they would hear all about it. … They all interacted with each other, knew each other. They began to fear that if one of us from the [treatment] center called them, it was because the product was being recalled (Lusher interview). On May 11, 1983, the Hemophilia Newsnotes referred to the recent recall by Baxter [Chapter Advisory #8, May 1983]. In August 1983, the NHF noted two additional recalls of contaminated lots, one by Baxter (Hyland Therapeutics) and one by the American Red Cross. The NHF sent a notification within days of learning of a recall. However, the NHF communications did not always reach the patient, and in some instances the information about the recalled product came from the pharmacy or the physician (Jason interview) and in some cases not at all (Kuhn interview).

In the case of individuals receiving blood transfusions, possible clinical options included autologous or directed donor programs. In the early years of the AIDS epidemic, patients were not always informed of the risks associated with blood transfusions (Alter, Crispen, Goldfinger, Silvergleid, interviews). In some cases, particularly in geographic areas known to be associated with a large number of high-risk individuals, patients were told that if they were going to have surgery to have blood drawn ahead of time if possible, or have a relative donate blood for them (Amman interview). However, directed donor and autologous donations were viewed with considerable skepticism in the blood bank community. Further, blood bank leaders have often viewed discussions of the risks of the blood supply as having a detrimental effect on donation and availability (see Chapter 5).

Case Studies

The following case studies are presented to illuminate what was communicated about the risks associated with the use of blood and blood products from the perspective of specific patients and physicians. They also provide information about the individual perceptions of possible clinical options that existed during this period of uncertainty.

Case Study One: Conviction and Change

The particular patient-physician relationship described here serves as an example of how important it was that both the individual with hemophilia and the treating physician arrive early at the belief that the risk of AIDS from using AHF concentrate was high and that cryoprecipitate was a feasible option.

Dr. Melvin Simonson 1 is a psychiatrist living in the Southeastern United States. He has severe hemophilia with a Factor IX deficiency. Dr. Simonson first became aware of the potential risk of exposure to AIDS from use of blood and blood products in October 1982. He remembered a particular news story as well as an article on T4/T8 reversed cell ratios in AIDS cases that appeared in the New England Journal of Medicine in 1982. Dr. Simonson's immediate response was one of panic, in all senses of the word. Dr. Simonson believed that the theories about AIDS (e.g., associated with the use of amyl nitrates, homosexual promiscuity) were wrong. He was convinced that if hemophiliacs were getting the disease, it had to be from use of the AHF concentrate products. Therefore it had to be in the blood supply and it had to be infectious.

Dr. Simonson went to speak with his physician, Dr. Arnold Schmal, who was serving on the Medical and Scientific Advisory Council of the National Hemophilia Foundation. Dr. Simonson discussed his beliefs about the risk of AIDS from AHF concentrate, and asked to be treated with fresh frozen plasma. When Dr. Simonson discussed the risk with other physicians at the same treatment center, he was told he was "overreacting, the risk was not that bad, there are always risks, and finally, let's wait and see what happens." However, his physician concurred with his concerns about the risk and believed that his request for an alternative treatment was rational. Furthermore, before AHF concentrate became standard treatment, Dr. Simonson had treated his disease with fresh frozen plasma successfully for 18 years. His physician was supportive and helped him to set up a directed donor plasma program. If he had a life threatening bleed during this time, Dr. Simonson believes that he probably would have used the AHF concentrate treatment.

Setting up a directed plasma donor program was not an easy task at the end of 1982. Dr. Simonson's initial attempts to work with the American Red Cross (ARC) were futile, as they were not receptive to the idea of such a program. He also tried to work with two universities' hemophilia treatment centers, however, both universities told him they only used donations for research projects and blood for clinical use was obtained from the Red Cross. In early 1983 Dr. Simonson located a private blood bank that agreed to assist him. To do this, he approached 20-30 personal friends and wrote a letter to colleagues in his professional society asking them to donate plasma necessary for his treatment. He started this program in February 1983. Dr. Simonson relied on this same group of individuals until February 1995 when he enrolled in a clinical trial for recombinant Factor IX. He remains HIV negative.

Case Study Two: Reduction in Use of AHF Concentrate

Dr. Eugene Baker is an example of a person who, because of his own concerns and unease about AIDS, sought out the advice of the medical community and received continual reassurances about the safety of the product he was using. His eventual change in behavior to reduce his use of AHF concentrate, and to later switch to cryoprecipitate, was actually self-initiated and subsequently reinforced by a physician who did believe that the AHF concentrate was contaminated with AIDS.

Dr. Baker came of age during the time when the world was changing for individuals with hemophilia. He is from Wisconsin, born in 1959, and is the second of two sons with severe hemophilia. For the first 10 years of his life he was treated with fresh frozen plasma. In 1969, his family physician prescribed a new product, cryoprecipitate, which he continued to use on an in-patient basis until 1974. In 1974, he was introduced to the AHF concentrates. His physician told him that there was a minimal risk of hepatitis. For Dr. Baker, the use of AHF concentrate made home infusion possible, and hospital stays were a thing of the past.

In 1976, Dr. Baker's older brother developed acute hepatitis. His brother survived, but at the age of 17 he was left with a lasting impression and growing fear about the possible transmission of hepatitis from using these blood products. When he queried various individuals in the medical community about the risk of hepatitis from the use of AHF concentrate, he was told that the hepatitis problem was due to the pooling of blood from thousands of paid donors, who were themselves at high risk for hepatitis.

In January 1981, Dr. Baker was told that he was negative for hepatitis A antibody and hepatitis B surface antigen, and positive for hepatitis B core antibody. His physician also told him that he should not be concerned about these findings. When he graduated from college in 1981, his bleeds were minor and easily treated with AHF concentrate. In the fall of 1981, he began graduate school.

He first became aware of a possible risk of AIDS from using blood products in the spring of 1982, when he read a scientific article that described an immune disorder diagnosed in a severe hemophiliac. The disease was predominantly associated with homosexual behavior, but he became concerned of the risk of this new disease being transmitted via the AHF products, because he knew how the product was manufactured. He made an appointment immediately with one of the hematologists at his university's hospital. The physician told him there were as many as 10 cases in hemophilia patients. He was told not to worry, that the National Hemophilia Foundation was advising hemophiliac patients not to change their treatment regimen.

In early 1983, Dr. Baker learned that the CDC had reported 11 additional cases of AIDS in hemophiliacs (CDC, MMWR, March 4, 1983). Again he questioned the hematologists at his school, and was told only a small fraction (1 percent) of the hemophiliacs were contracting the disease and that the etiology was not yet known. His physicians reassured him that it was the position of the NHF, as well as the plasma fractionators, not to withhold or reduce treatment. Dr. Baker made the decision to use the product sparingly. In August 1983, he discussed his decision with his older brother and learned that he was not reducing his use, and in fact had even planned elective surgery for early the next year.

In September 1983, Dr. Baker began to have digestive problems involving bouts of diarrhea; he knew this was one of the symptoms of AIDS and became quite fearful. He also knew that as a severe hemophiliac he was now a member of a high-risk group for developing AIDS. His physician conducted some initial tests that proved inconclusive, and antibiotics prescribed by his physician had no effect. His physician administered an immunological test, and one week later he received a letter from his physician saying that he had a very low T4 count and an inverted T4/T8 ratio. His physician told him that he may have a mild case of AIDS, but not to worry because there were many new experimental treatments.

Later the same month, Dr. Baker made an appointment with another physician for a second opinion. This physician did not agree with the initial diagnosis of AIDS because of the absence of any of the symptoms usually associated with AIDS (i.e., PCP, Kaposi's sarcoma). He queried his physician about the possibility that AHF concentrates were infected with the AIDS virus. The physician stated that he believed that they were, but expressed caution that this was not the position of the NHF or the plasma fractionation companies. Dr. Baker demanded an alternative treatment that would reduce his risk; the physician told him the best thing would be to go back to cryoprecipitate obtained from voluntary donors.

It was not the physician, but Dr. Baker himself, who had to try to make these arrangements. He contacted the American Red Cross and was not given much help with his specific request. He was told that cryoprecipitate was made only in small quantities for special needs and that it would not be possible to accommodate the needs of all hemophiliacs.

In October 1983, Baker scheduled appointments with several other physicians at the university (this included a longtime family hematologist). At this juncture, he was told that the risk of AIDS was small and that he should neither reduce therapy nor return to cryoprecipitate (he was told that this was the position of the NHF and plasmapheresis companies). He was adamant and persistent; finally someone at the local chapter of the ARC agreed to supply him with the necessary cryoprecipitate. He infused himself at home and stored the cryoprecipitate in his freezer. During this time his T4 cell count remained abnormal, and he continued to have frequent digestive problems.

In March 1984, Dr. Baker's brother underwent his scheduled elective surgery. His brother was told that the risk of AIDS was almost nonexistent. Three weeks after the surgery, his brother developed night sweats, fever, and unexplained weight loss. In March 1985, his brother started to develop serious health problems, which were a result of AIDS and an acute brain infection. The new HIV antibody test revealed that his brother was HIV positive. His brother died in June 1985.

In August 1986, Dr. Baker began to pursue a Ph.D. He treated his hemophilia with heat-treated AHF concentrate at first, and then switched to monoclonal antibody products when they became available. Despite his low T4 count, he was in good health. In October and November of 1986, he participated in clinical trials of AZT therapy, which initially, but only temporarily, increased his low T4 cell counts. In November 1989, Dr. Baker tested positive for HIV. In December 1990, he was awarded his Ph.D. and became a nutritional consultant. He also continued to participate in clinical trials. At this time, his T4 cell count had dropped below 50.

By December 1994, his physician told him to take full and permanent leave from his employer for reasons of declining health. He disclosed his HIV status to his friends and colleagues. Currently he is on an array of antiviral and other medications. He also suffers from liver disease from a hepatitis C infection.

Dr. Baker believes that erroneous and misleading information was provided to patients from the pharmaceutical companies. He believes that the NHF neglected its responsibilities to the people they were supposed to be serving by inadequately warning patients of the risks involved with using the concentrates. He is convinced that treatment options to reduce the risk of infections were not discussed or disclosed to the hemophiliac community, and that the physicians treating hemophiliacs either were not told of the risks or were misled into believing that the risks were low.

Case Study Three: Continue AHF Concentrate Treatment

This case study illuminates the influence of situational factors, or personal experience, on the perception of risk and changes in behavior. It is from the perspective of a physician of one of the larger hemophilia treatment centers where 400–500 active patients are seen at least once per year.

Dr. Susan David first became aware of the possible risk of AIDS sometime in 1981, primarily through the media attention. She believed AIDS, known then as "GRID" (gay-related immunodeficiency disease) was a problem in the homosexual population. Dr. David remembers receiving the CDC's Morbidity and Mortality Weekly Report (MMWR) in July 1982, the first report of AIDS in three people with hemophilia.

In November 1982, the CDC sent a very detailed survey to the treatment center requesting information on the number of patients with enlarged nodes and the causes of death in hemophilia patients over the past 10 years. Completing the survey was an administrative burden, and Dr. David phoned CDC to see why the information was required. She was told that they were investigating whether AIDS was a real problem in the hemophilia population. Sometime close to Thanksgiving, Dr. David remembered a 12-year-old boy who had a bleed and enlarged lymph nodes. The child was not sick and she recalled wondering if the child's enlarged lymph nodes were relevant to the reports in the MMWR and the information that the CDC was requesting.

In early December, Dr. David learned of the case of the baby in San Francisco who had possibly gotten AIDS from a transfusion (see Chapter 3). At this point, the staff among the treatment center began to talk about the new disorder. In December, one of the physicians suggested arranging directed donor programs for patients who were put on cryoprecipitate, but this suggestion was not implemented; nor was another suggestion to use a preparation of only female-donated AHF concentrate prepared by one of the plasma fractionation companies.

On January 3, 1983, the treatment center held a meeting for all of the center's patients, families, and other interested persons. Its purpose was to discuss the risk of blood and plasma transfusion therapy to hemophiliacs, and it was attended by approximately 100 people. At this point, the staff told the patients and families that they were cooperating with the CDC survey, they saw no reason to change treatment at this time, and they were trying to get more information. The message to the patients was to keep in touch with the treatment center.

On January 4, 1983, Dr. David attended the CDC meeting in Atlanta (see Chapter 3 and Chapter 5). She did not agree with the blood bank community's decision not to implement direct questioning of donors, but did agree about not implementing surrogate testing (i.e., the hepatitis anti-core test) for AIDS. As a physician at a major hospital, she was concerned about maintaining an adequate blood supply for transfusions and the surgical work that was done at the hospital. Clinical care continued as usual, although a bulletin describing what was known about AIDS was issued by the treatment center to patients following the January 4, 1983, meeting.

In the latter half of 1983, the treatment center held another meeting with patients and their families. At this time, according to Dr. David, the center was following the advice of the NHF, "not word for word, but in accord with their recommendations." In addition, by the first half of 1983 the treatment center's pediatrician changed the younger children's treatment to cryoprecipitate. By April 1983, the first heat-treated product had been licensed by the FDA and the center debated its use, weighing the expense of the new product with the unknown potential problem of inhibitor formation. According to Dr. David, heat treatment was originally developed for hepatitis inactivation. Dr. David stated that hepatitis did not seem like a terrible risk in 1983, so the benefit of heat treatment for reducing hepatitis risks was not an impressive safety feature. The physicians decided to selectively use the heat-treated products; heat-treated AHF concentrate was given to patients who were known to not have been exposed to hepatitis. The center's staff also decided that patients should treat bleeds promptly, but to have them reduce use of AHF concentrate whenever possible. Dr. David personally believed that patients significantly overused AHF concentrate. At this time, the treatment center, with its large number of patients, had still not seen a single case. They were convinced that the risk was small. They also decided to resume elective surgeries because of the many requests that were made by the patients and because of the organization of a prospective surgery study of the immune system.

According to Dr. David, there were lengthy discussions about AIDS among the scientists and physicians at the Stockholm meeting of the World Hemophilia Federation in May 1983. The final conclusions were that no one knew what to do; there was no indication to change treatment. After the meeting, she talked to the head of the local chapter of the American Red Cross about producing more cryoprecipitate. This official was not receptive because an increase in production would have placed a tremendous burden on the system. Dr. David stated that she did give her patients the option of using cryoprecipitate, but not many patients decided to use it. One theory was that because that area had a high prevalence of AIDS in homosexual men, who had been donating to the blood supply, it was likely that HIV was in the donor pool and that cryoprecipitate would transmit AIDS as well. Logistically, the treatment center could not possibly have switched everyone to cryoprecipitate; but patients were given the option.

By the end of 1983, everyone at the center realized that there was likely an infectious agent in AHF concentrate and that both blood and cryoprecipitate were transmitting it. The only options were to offer cryoprecipitate (which no one took), to suspend surgeries, and try to get the patients to reduce their consumption of AHF concentrate.

In January 1984, the center diagnosed their first case of clinical AIDS in a young man, who died within a week of his diagnosis. This was soon followed by a second case. Dr. David phoned Bruce Evatt, a scientist at CDC, who remarked, "It is really happening now." The response, according to Dr. David, however, was not dramatic: "We still did not make any change. Each doctor at the treatment center prescribed AHF concentrate according to his or her best judgment. I did not use a lot of heat-treated AHF concentrate because at this point I believed that everyone who had received a lot of AHF concentrate was already exposed, the cost of heat-treated products was very high, and I was still worried about the side effects [inhibitors]."

In May of 1984, one of Dr. David's patients, a teenage boy, died from an untreated head bleed. He had hit his head in an accident at home, resulting in an intracranial bleed. He did not treat his injury with AHF concentrate and he subsequently died. According to Dr. David, everyone at the treatment center was shocked. It was evident to her that if you told patients to cut down on AHF concentrate use, it could be a catastrophic event for all hemophilic patients. According to Dr. David, "this one case influenced our thinking."

The center had an influential role in transmitting information to physicians about what to do. According to Dr. David, "We got phone call after phone call. We knew that it was transmissible, but to translate that to a plan of action was difficult, as there was not any plan of action that seemed coherent. A huge change in treatment may have endangered lives. The patients knew basically what we knew."

In reflecting on lessons learned, Dr. David perceived the FDA and the NIH as remote entities that had no influence on daily practice. In addition, Dr. David stated that most of the information on AIDS came from the NHF and their bulletins, and personal contacts. She said, "The FDA did not realize that the NHF and from MASAC represented a certain small group of doctors and how much was getting out to the hemophilia community was a little bit questionable. The grassroots level was really doing its own thing. Our group was more in the middle, and I think that I was more advanced because I had many informal contacts."

Case Study Four: Prescribing Cryoprecipitate for a Newborn and Continuing AHF Concentrate Treatment for a Four-Year-Old

This case study is about a father who relied on and trusted the medical experts (i.e., MASAC and other physicians) and did not question the NHF recommendations made on January 14, 1983 (i.e., to treat newborns, newly diagnosed hemophiliacs, children under four, and mild hemophiliacs with cryoprecipitate, and to continue to treat others with AHF concentrate).

Robert Thomas is a father of two sons with severe hemophilia, both born during the period when HIV was entering the blood supply. His older son, John, born in 1979, is HIV positive; his younger son Steven, born in 1982, is not.

When Mr. Thomas's first son was born, the new father did not know anything about hemophilia. His son had his first bleed in March 1980, when he was eight months old. The physician tested him and Mr. Thomas was told that his son was a hemophiliac. Initially, he was not concerned about the risk of hepatitis, because he was overwhelmed with learning how to deal with hemophilia. He soon learned to "roll with it" and became comfortable with the treatment recommended by his physician. He learned that hemophilia could be easily treated through the use of AHF concentrate, which was infused by the staff at the hospital. Reflecting on this, Mr. Thomas stated that "he did not know enough to ask a lot of intelligent questions, and did not understand enough to be assertive." After this, his son did not receive many infusions until he was 15 months old. On October 31, 1980, his son had surgery for a blot clot in his spinal cord that had left him paralyzed. During surgery he received thousands of units of AHF concentrate. The surgery was not successful; his son remained paralyzed. At some point, his son contracted post-transfusion chronic hepatitis infection.

In 1981, Mr. Thomas decided to join his local chapter of the National Hemophilia Foundation, and he became its president. The active membership of the chapter, at the time, consisted of five members: an individual with hemophilia, Mr. Thomas, and three other parents of individuals with hemophilia. There was one chapter in the state. While there were several hundred individuals with hemophilia in the state, most of the adults had their own physicians or were affiliated with either one of the two major hospitals serving the population at that time. According to Mr. Thomas, the other reason for the low membership in the chapter was a "general lack of interest by most of the hemophiliac community at that time."

Mr. Thomas's second son, Steven, born in early 1982, had severe hemophilia. Mr. Thomas first became aware of a possible risk of AIDS from using blood products in July 1982, when he received the first patient alert from the NHF (July 14, 1982). In October 1982, Steven had a bleed. He went to the hospital and was told by the hematologist, "There are just too many unknowns about Factor VIII concentrate right now; we need to treat your son with cryoprecipitate." Mr. Thomas asked, "What about my other son?" The physician told him that since he was already on the AHF concentrate, he should continue to use it, and that the NHF was recommending that treatment with concentrate be continued, except when indicated by overriding medical concerns. In October 1982, Mr. Thomas's older son, John, was only three years old.

As president of the local NHF chapter, Mr. Thomas said, he sent out the NHF alerts to 90 percent of the hemophiliacs in the state. Mr. Thomas said that he did not discuss the decision to put his younger son on cryoprecipitate with other chapter members. He remembers that most people (himself included) were occupied learning how to home infuse.

Mr. Thomas continued to have the hospital medical staff infuse his older son with the AHF concentrate. He states he was led to believe that if he did not adhere to this treatment, his son would die from a bleed. Mr. Thomas recalls that, "the potential of a life-threatening bleed was a message reiterated in every NHF alert and bulletin and physician/patient discussions."

In August of 1983, Mr. Thomas received a booklet from Alpha Therapeutic Corporation that contained information about what was known from the AIDS cases that had recently been diagnosed in a small number of hemophiliacs. The following is a synopsis of the information put together by the medical director of Alpha Therapeutic to inform the patients using AHF concentrate.

Alpha was concerned about what it referred to as, "a newly-recognized—and apparently new—disorder." It told its readers that in cases of AIDS, the body's immune system was altered and functioned less efficiently. Its victims "may be afflicted with severe infections, including a rare and deadly form of pneumonia, and other illnesses which their bodies would normally be able to resist. Many AIDS victims die as a result of immune deficiency. The commonest causes of death have been Pneumocystis carinii pneumonia and an unusual cancer, Kaposi sarcoma." The booklet also stated that "AIDS was discovered in, and is still largely confined to, bi-sexual or male homosexuals," and also occurred in IV drug users, and Haitian immigrants. The reader was informed that AIDS was found in a hemophilia patient who did not belong in any of the high-risk groups in March 1982. As of March 1983, there were 11 additional cases in hemophiliacs, 9 of 12 had died. According to the booklet, ''hemophilia patients now constitute about one percent of AIDS victims. More importantly, only about one in every thousand hemophilia patients has developed AIDS." The readers were informed that the cause was unknown, but it was possible that it was transmissible.

Mr. Thomas looks back and does not understand how the recommendation could have been made to treat his newborn with cryoprecipitate, but continue to treat his three-year-old with concentrate. He believes there was a clear double standard in this recommendation derived from the manufacturer's desire to sell their factor concentrate. Mr. Thomas' three-year-old son weighed less than 40 pounds. Therefore, the reason given that only young children, because of low body weight, could be effectively treated with cryoprecipitate to stop bleeds was inapplicable to Mr. Thomas' three-year-old. Furthermore, Mr. Thomas believes that both his sons should have been using cryoprecipitate unless a life-threatening situation necessitated the use of concentrate. He asks, "How could any medical professional or anyone in the blood industry logically come up with these recommendations? Were hemophiliacs who contracted HIV from AHF concentrate an acceptable loss from a business standpoint?"

Case Study Five: A Transfusion Case

In 1980, Elizabeth Glaser, 2 when she was six months pregnant, began hemorrhaging. She was rushed to the hospital, where after the delivery of her daughter, Ariel, she was transfused with seven pints of blood. In 1984, Glaser gave birth to her son, Jake. In September 1985, Ariel became ill with serious and baffling stomach pain and fatigue. From January to April 1986, a series of tests revealed nothing. The belief at the time was that an individual needed direct contact with blood or semen to get AIDS. Mrs. Glaser recalled that, "There was nothing about breast milk as a source of transmission." One of the physicians wanted Ariel tested for AIDS because of Elizabeth's transfusions. The test came back positive and the family learned that Ariel had a disease called AIDS. "I screamed as loud as I could. My life was over … my daughter is going to die" (Glaser and Palmer 1991).

Mrs. Glaser's physicians determined that she had received contaminated blood and had unknowingly passed on the HIV infection to her daughter Ariel through breastfeeding and in utero to her son Jake. For the family "It was our worst nightmare … It was too much to comprehend." The family learned that there were no drugs or treatments that could make Ariel well. Elizabeth, her husband Paul, and their son Jake, were also tested for HIV in 1986. Mrs. Glaser learned that she and her son were HIV positive, but her husband was not. Although Mrs. Glaser had unknowingly passed on the HIV infection to her son, her husband remained HIV negative.

Elizabeth and her family struggled with the isolation that they experienced after they disclosed their problem to their friends, at a time when "there were no assurances to give them that this was not a risk for their children, unlike now." Ariel had to be taken out of summer camp because no AIDS children were allowed there, and when they did tell more people, some would not let their children play with Ariel and Jake.

Elizabeth Glaser's daughter continued to grow weak and frail. In February 1988, Ariel stopped walking. In March she was hospitalized for pneumonia and her physician said her brain was severely atrophied; she lost her ability to speak. Ariel recovered briefly from the pneumonia, was put on AZT, and died in August, shortly after her seventh birthday.

Elizabeth Glaser became a public symbol of the AIDS tragedy in this country. She became active in policy for increased funding for pediatric AIDS research. In 1989, she helped to establish the nonprofit Pediatric AIDS Foundation. On December 3, 1994, at the age of 47, Mrs. Glaser lost her battle against AIDS (McCormick 1993).

Summary of the Case Studies

In the course of the Committee's investigation, many individuals were interviewed about how clinical options were evaluated and in some instances implemented. The case studies indicate how certain options were evaluated by physicians and patients. In some instances options were considered and discarded; in others, clinical options were never fully assessed and discussed between physicians and patients. In yet other instances there were potential inconsistencies in the clinical options. The case studies provide a window into the risk/benefit calculus as physicians and patients confronted the increasing risks of blood and blood products.

The case studies help demonstrate how individuals pursued, or failed to pursue, various clinical options. In the first case, the individual was acutely aware early on in the AIDS epidemic of the risks posed by using blood and blood products. This individual aggressively pursued an alternative option (i.e., a directed donor cryoprecipitate program) with the support of his physician. In the second case, the individual also became apprehensive about the potential risks at an early date, but physicians reassured him that the AHF treatment was safe, the risk of infection was small, and the treatment regimen should be maintained. The third case reveals the difficulties of weighing treatment options, in particular the reduced use of the AHF concentrate and the possible consequences if the patient decides not to treat certain bleeds. The fourth case demonstrates the inconsistencies in the manner in which treatment options were sometimes portrayed. A father was confronted with the decision to treat his newborn son with cryoprecipitate and to maintain AHF concentrate treatment for his older son. Finally, the fifth case illustrates how the options for a transfusion recipient were not communicated even though the assessments of the risk of contracting AIDS through blood transfusions were increasing.

Obstacles To Communication

Institutional Obstacles

In its examination of institutional obstacles to communication of risks the Committee has three major findings. These concern: (1) the resources and expertise of the NHF and MASAC; (2) the relationship of the NHF with the plasma fractionators, which ultimately cast doubts on the ability of the NHF to produce authoritative, objective recommendations in the absence of any governmental authority; and (3) the style that the NHF assumed in communicating with both the providers of hemophilia treatment and the individuals who had hemophilia.

Resources and Expertise of the NHF

As the AIDS crisis emerged, the NHF stepped into an institutional vacuum, taking on the critical responsibility for communicating to individuals with hemophilia about the risks associated with the use of blood and blood products. Serving as a liaison between government agencies and the hemophilia community, the NHF (with the help of MASAC), established itself as the primary source of information for individuals who used blood products (Brownstein 1994; Aledort, Carman, Levine interviews). At that time, the NHF was the only national organization enjoying a combination of expertise (through MASAC) in treating individuals with bleeding disorders, the confidence of hemophiliac patients and their physicians, and a reputation among government and industry leaders as representing the interests of individuals with hemophilia. While the federally funded hemophilia treatment centers disseminated information to their patients, the NHF communications provided the basis for assessment of the risk and the development of treatment options. In addition, most members of MASAC were associated with individual treatment centers.

Despite the system of federally funded treatment centers, there was no universal system for notifying patients about risks associated with blood and blood products, and consequently not all individuals in the hemophilia community were informed. In 1982, 50–70 percent of the hemophiliac patients in the United States were members of local NHF chapters or received treatment through the hemophilia treatment centers (Evatt pers. comm., 1995; Smith and Levine, 1984; Aledort, Kasper, Hoyer interviews). In addition, patients in geographically remote areas were especially likely to have less access to treatment and risk information, and some areas had no treatment centers. In these instances, hemophiliac patients were apt to receive AHF concentrates through their local hospital's pharmaceutical dispensation centers (Jason, Reumke interviews). The NHF's early involvement in policy debates and its vigilance in tracking the trajectory of the disease were not matched by comparable efforts to communicate directly with patients. Local chapters owned their own mailing lists, as did the treatment centers, and the NHF left to individual chapters and treatment centers any decision to mail or otherwise distribute information received from the NHF to members (Brownstein 1994; Bias, Carman interviews). The Committee learned that in some instances chapters and treatment centers had insufficient resources for dissemination of NHF mailings (Bias interview). Hence, information sent by the NHF to the treatment centers of NHF chapters did not reach many of the hemophiliacs. Moreover, there was no national registry of hemophiliac patients or treating physicians that the NHF or government agencies could use to communicate directly with hemophiliacs (Bias, Hoyer interviews; Brownstein 1994). In 1981, the NHF tried to compile a registry of all hemophiliac patients but failed owing to confidentiality concerns. The NHF tried again in 1992 but listed only 7,000–8,000 out of as many of 16,000, indicating the problem with reaching the total hemophilia population (Brownstein 1994). Some chapters had low memberships at the time because of a general lack of interest, and most hemophiliacs were on home infusion programs and were not dependent on the chapters and treatment centers. In addition, many hemophiliac patients had private physicians who were not associated with the treatment centers. In one state that had several hundred residents with hemophilia, only five were members of the chapter (Reumke interview).

In the early 1980s, the NHF and MASAC had neither the experience nor adequate expertise to provide specific recommendations to reduce the risk of HIV infection. The NHF had been a nonprofit health organization with interests specifically focused on maintaining federal funding for treatment centers and responding to more general needs of the hemophilia community through local chapter affiliation. When the NHF reactivated MASAC in October 1982, it was comprised of experts in the physical and psychological aspects of the disease and its treatment. These individuals were, by and large, elected to MASAC through the regional treatment centers. Thus, although they had the respect, trust, and support of many in the hemophilia community (Bias, Carman, Hoyer, interviews), their expertise did not extend to all aspects of HIV and its putative transmission through blood products. In addition, the NHF leadership could appoint several members to MASAC (Carman interview). In the early 1980s, however, there was no expertise within MASAC in such areas as infectious disease, epidemiology, or decision analysis. The Committee concluded that the MASAC or NHF leadership did not have all the expertise required to assess the information about the nature and severity of risk as it became available and to understand the possible ramifications of the transmission.

One caveat, however, is necessary. Although the NHF, and MASAC in particular, may have lacked expertise in the critical areas, it did include among its membership some of the nation's most respected physicians involved with treatment of hemophiliac patients. In this respect, at least, the NHF arguably was in a unique position to give careful and informed consideration to the range of possible clinical options that patients and their physicians should consider.

The NHF and the Plasma Fractionation Industry

A second important finding of the Committee was that the NHF and the plasma fractionators had developed close ties that may have compromised the independence of the NHF treatment recommendations. Over the years, the NHF and treatment center physicians had worked closely with the plasma fractionators to develop AHF concentrate. Leaders in the hemophilia field described the relationship to the Committee as synergistic (Hammes pers. com. 1995; Aledort, Carman, Levine interviews). Physicians participated in industry's clinical trials of AHF product, they assisted in the development of information brochures produced by the plasma fractionators about the product, and NHF benefited from industry's financial support of its various committees (e.g., the Nursing Committee) and program meetings (Brownstein 1994; Carman interview). In the Committee's judgment, this close and interdependent relationship led to the perception that the recommendations provided by the NHF and MASAC reflected conflicts of interest, were not adequately objective, and seriously compromised NHF's credibility.

Communication Style of the NHF

The Committee's third finding is that the leadership of the NHF, until October 1984, adopted a generally paternalistic style of communicating information to physicians and patients in which, instead of presenting the rationale for their conclusions and the range of treatment options which they themselves considered in private meetings, the NHF disseminated only their conclusions. These conclusions were accompanied by strongly worded admonishments against reduced use of AHF concentrate. As a group composed of blood disorder specialists, MASAC exhibited a strong tendency to maintain existing treatment regimens and to make only incremental modifications in clinical practice. Until October 1984, NHF communications minimized the potential risk and the extent of possible infection within the hemophilia community and avoided publishing information that individuals with hemophilia and their physicians could utilize to make their own risk assessments and medical decisions.

A more general institutional concern is the fact that the NHF exhibited some tension in the ways in which it defined and carried out its own mission. Executive Director Alan Brownstein, expressing his views about the role of directors of hemophilia societies in an address to the World Hemophilia Federation Conference in June 1983, emphasized the aim of becoming "the source" of information about AIDS and hemophilia. To that end, according to Brownstein, the NHF had decided to retain tight control of the flow of information, to impose strict discipline on who would speak for the NHF, to allay public fears exacerbated by media reports, and "to spread the message throughout the land that clotting factor use should be maintained" (Brownstein 1983). The possible difficulty with the vision of NHF expressed by Brownstein is that goals with respect to institution-building may have been in conflict with and have even overshadowed the commitment to meeting the informational needs of the organization's constituency. One consequence of the NHF's efforts, in the Committee's view, was to restrict rather than to increase the flow of information that patients and their physicians could have used in their own individual medical decisionmaking.

Social and Cultural Obstacles

Several social and cultural impediments in the relationships between patients and physicians interfered with the communication of information about the risks associated with using blood and blood products. These included the tendency of physicians to not discuss, or to downplay and deny, the risk of AIDS; the confidence of physicians and patients in the benefits of AHF concentrate; the context of hepatitis as a medically acceptable risk; the difficulties of communicating dire news to patients; and the problems associated with communicating uncertainty.

With reports of the Committee's finding that physicians tended to avoid, downplay, or deny the possible risk associated with the use of blood and blood products, one of the case studies revealed that physicians often responded to the initial questions of patients with reassurances that the risk was not serious, that the patient was overreacting, that "there are always risks," and that patients and doctors should wait and see what happens (see Case Study One). Or, the physician conveyed the impression that the risk was a problem associated with homosexual behavior and therefore not a problem for individuals with hemophilia (see Case Study One; Bias, Dietrich interviews). In addition, physicians downplayed the size of the risk, saying, for example, "that the patient need to be concerned because only one percent of hemophiliacs were contracting the disease" (see Case Study Two). Information from the NHF and the treatment centers repeated these messages. For example, in a February 1983 newsletter one hemophilia treatment center [Regional Comprehensive Hemophilia Center of Central and Northern Illinois] told patients that "out of some 20,000 hemophiliacs in the U.S., about 10,000 with severe hemophilia A, who have been transfusing some 500 million units of factor VIII each year, only eight or ten have developed AIDS." Similar estimates appeared in information sent to individuals with hemophilia by the plasma fractionation industry.

In assessing the risks associated with using blood and blood products, physicians emphasized the known benefits of AHF concentrate and underweighted the risks of AIDS, which were still uncertain. The NHF and MASAC assessment weighed the benefits of AHF concentrates against what it perceived as "small numbers of AIDS cases in hemophiliacs," and recommended a firm policy to adhere to AHF concentrate therapy rather than cryoprecipitate. Some physicians believed that any change in treatment would endanger the lives of their patients and that the good quality of life with AHF concentrate outweighed the uncertainties of AIDS risk and prognosis (Aledort, Dietrich interviews). In their risk-benefit analysis, physicians believed that the probability of getting AIDS was lower than the probability of morbidity from nontreatment (Aledort interview). Whereas many in the hemophilia treatment community knew the morbidity and mortality attributable to decreased use of AHF concentrate, the morbidity and mortality from AIDS was unknown (Aledort, Carman, Dietrich, Kasper, Levine, Lusher interviews).

Individuals with hemophilia had similar perspectives (Bias, Wadleigh, Dubin, Botelho interviews). According to Bias, "One theory was that hemophiliacs would develop antibodies, like hepatitis, and would not be infected. This was coupled with the desire to lead a normal life" (Bias interview). In one case study (Case Study Four), the father of two sons with hemophilia believed that if he stopped using the AHF concentrate treatment prescribed by his son's physician, the boy would bleed to death.

Some of the attitudes of the patients and their physicians originated in the 1970s when hepatitis emerged as an infectious complication in patients receiving blood and blood products (see Chapter 4). In the context of hemophilia treatment, hepatitis became a medically acceptable risk. In the beginning, HIV engendered analogous attitudes (Lusher interview). Although hepatitis infections were occasionally severe, leading to liver failure and death, it was clear to many physicians that the benefits of the AHF concentrate treatment or the blood transfusion outweighed the disability from the hepatitis (Aledort, Alter, Goldfinger, Hoyer, Johnson, Levine, Lusher interviews). Hepatitis was seen as well understood and manageable: "We used to deal with hepatitis, you get it from blood, it was well established. No one got sick right away … and it was not life-threatening" (Alter interview). Individuals with hemophilia knew that hepatitis was a problem associated with using AHF concentrate derived from pooled plasma from thousands of individuals (see Case Study Four; Aledort interview). Hepatitis was "acceptable," and individuals with hemophilia were told not to be concerned about it (case study four; Bias interview). When AIDS appeared in the early 1980s, the first reaction of both physicians and individuals was that this new problem would also be manageable (Case Study Three; Bias, Botelho, Louvrein interviews; Pierce 1983). "The response of the patients was not one of fear, and the parents of hemophiliacs were getting used to the risks involved with hemophilia" (Louvrein interview).

As late as the end of 1984, the number of hemophiliacs with AIDS was small compared to the number of patients who received AHF concentrate, and some MASAC members doubted that the infection would become widespread among hemophiliacs (Aledort, Carman, Lusher interviews). Their judgment was due to the then widespread misunderstanding of the length of the latency period in HIV infection and thus what was assessed as the small number of patients with AIDS relative to the number with HIV infection.

As the recognition of the risks of infection with AIDS grew during the period between early 1983 and mid-1984, physicians and other providers of hemophilia care began to assume that most of their patients might already be infected. This assumption also contributed to the rationale to maintain treatment regimens with AHF concentrate. If patients were already infected, changing to cryoprecipitate would only lead to suboptimal treatment for the symptoms of hemophilia; it would no longer reduce the risk of infection. Therefore, many physicians decided not to change their approaches to treatment. The Committee believes that these explanations do not provide sufficient justification for the NHF's decision to communicate only its conclusions rather than provide patients and physicians with the information needed for them to reach their own conclusions.

The doctrine of informed consent—communication of information and discussion of treatment alternatives and risks by physicians to their patients—has long been recognized as a central moral and legal tenet of medical practice in the United States (Katz 1986; Faden and Beauchamp 1985). While it had entered clinical practice by the early 1920s, by the late 1950s, the legal duty to obtain consent had evolved to include an explicit duty of physicians to disclose to patients medical information relevant to making a decision about treatment [Salgo et al. v Leland Stanford, Jr., 1957]. However, in some special medical practices, such as hemophilia and transfusion medicine, it was not fully adhered to until the early 1980s. However, court opinions during this era qualified the duty of disclosure by permitting physicians to exercise discretion when full disclosure was deemed medically inappropriate. As Jay Katz has observed, both law and society more generally reflected a fundamental ambivalence between a commitment to patient self-determination and traditional practices of medical paternalism (Katz 1986).

By the early 1970s, however, the ambivalence was replaced by a more stringent conception of the duty of physicians to disclose all relevant information to patients. In Canterbury v. Spence, the first and most influential of a series of court cases in the 1970s, the court held: "[T]he patient's right of self-determination shapes the boundaries of the duty to reveal. That right can be effectively exercised only if the patient possesses enough information to enable an intelligent choice" [464 F. 2d 772, 786 (D.C. Cir 1972)]. Faden and Beauchamp, in their authoritative treatise A History and Theory of Informed Consent, summarize the impact of Canterbury and other cases from this period as follows: "[These cases] recognized that although professional expertise is necessary in identifying the nature and consequences of the procedure, the feasibility of alternatives, and the severity of risks, once the physician has exercised medical judgment in developing and presenting this information to the patient, further deference to the physician's judgment is unnecessarily in derogation of the patient's decisionmaking right" (Faden and Beauchamp 1985). An influential 1980 California Supreme Court case, Truman v. Thomas, represented the logical culmination of the changes in judicial attitude about matters requiring disclosure. The Truman decision made it clear that a physician's duty of disclosure encompasses discussions of all relevant treatment options, including the option of nontreatment and its attendant risks and benefits [165 Cal. Rpter, 308, 611 P 2d902 (Cal. 1980)].

The decade of the 1970s thus closed with a legacy of litigation that fundamentally changed the common law of informed consent in most states, and in half of the states newly enacted legislation replaced the remnants of the common law with explicit requirements for adequate disclosures (President's Commission for the Study of Ethical Problems in Medicine and Behavioral Research, 1983). These changes in the law reflected an emerging social consensus on the importance of full disclosure of information to patients for the exercise of the patient's right of self-determination. This new consensus also rested on grounds other than the rationale embodied in the law. Medical ethicists such as Robert Veatch (1982) of the Hastings Institute argued that informing patients of treatment alternatives so that they can participate in or control the decisionmaking process increases the likelihood that benefits to individual patients will be maximized and other social objectives such as improved medical decisionmaking would be achieved [DHEW Publication No. 78-0014, 1982]. Indeed, a substantial body of empirical literature demonstrates that enhanced communication and discussion of treatment alternatives and risks improves patient satisfaction, understanding and deliberation, adherence to treatment, and medical outcomes (Levine, et al. 1979; Eraker, et al. 1988; Hall, et al. 1988).

The norms of full disclosure of the benefits and risks of alternative treatment options had become deeply entrenched in clinical practice by the early 1980s. The best evidence of how pervasive these norms had become can be found in a 1981 statement of the Judicial Council of the American Medical Association:

The patient's right of self-decision can be effectively exercised only if the patient possesses enough information to enable an intelligent choice. The patient should make his own determination on treatment. Informed consent is a basic social policy for which exceptions are permitted: (1) where the patient is unconscious or otherwise incapable of consenting and harm from failure to treat is imminent; or (2) when the risk-disclosure poses such a serious psychological threat of detriment to the patient as to be medically contraindicated. Social policy does not accept the paternalistic view that the physicians may remain silent because divulgence might prompt the patient to forego needed therapy. Rational, informed patients should not be expected to act uniformly, even under similar circumstances, in agreeing to or refusing treatment [emphasis added] [Judicial Council of the American Medical Association, 1984].

This review of the history of informed consent illuminates how the practice of hemophilia and transfusion medicine was somewhat removed from recognized medical norms.

The Committee also found that some physicians were reluctant to discuss bad news, including a prognosis with dire implications, once symptoms of AIDS began to occur in their patients. Even when confronted with initial symptoms of AIDS, the physician's message to his patient sometimes was to not worry (see Case Study Four). The appearance of AIDS in a previously healthy individual with hemophilia became a frightening experience for physicians (Hoyer interview). Once physicians realized that the majority of individuals with severe hemophilia were infected with HIV, they became uncomfortable with discussing the implications of the widespread infection with their patients (Dietrich, Dubin, Levine, Kasper, Lusher, Wadleigh interviews).

In addition, medical uncertainty about the incidence of the infection caused difficulties in communications between physicians and their patients (Aledort, Carman, Crispen, Dietrich, Kasper, Louvrein, Lusher, Silvergleid interviews). According to one physician, "somehow there were enough different things being conveyed, different theories, and a lot of opposition to the idea that all of the clotting factor was contaminated. And, [there was] a lot of unknown[s] about whether or not we did have any alternative; whether or not heat treatment would kill the virus or whatever was causing AIDS, so that really nothing was done" (Lusher interview).

Under the uncertainty posed by the risk of blood-borne transmission of AIDS, many physicians attempted to communicate risks to their patients using strategies to present information gently [The Hemophilia Bulletin, Orthopedic Hospital, January 1983; Regional Comprehensive Hemophilia Center of Central and Northern Illinois, February 1983] as if to counter the effect of information that patients had heard from more alarmist sources, such as the public media (Levine interview).

The public media played an important role in raising the consciousness of hemophilia patients about their risk of AIDS. Physicians became concerned because many of the patients were reducing their use of AHF concentrate (Dietrich, Levine interviews). In some instances, physicians believed that one of the reasons patients were reducing their use was because of the public media: ''You couldn't open a newspaper or magazine without seeing an AIDS patient along with language linking it to hemophilia. So we went through late 1983 and early 1984 seeing many patients withholding treatment. You had people come in with horrible lesions that you had gotten used to not seeing anymore" (Levine interview). Counteracting media attention was one reason for the NHF policy of urging treatment physicians to reassure patients that the risk of AIDS was low and to maintain their use of AHF treatment (Carman interview). In the early days of AIDS in hemophilia patients, there were many examples of ill effects of reducing use of AHF concentrate and few patients with symptoms and signs of AIDS. By the end of 1983, one of the largest hemophilia treatment hospitals had not yet seen a case of AIDS in their patients but they did have a young child die from intracranial bleeding because the person was afraid of the treatment (Dietrich interview). The death of the young hemophiliac from an intracranial bleed reinforced physicians' fears and beliefs of how important it was to maintain treatment. Soon, AIDS would appear in hemophilia patients, and there would be second thoughts about the balance of risk and benefit from AHF concentrate treatment.

The uncertainty of the AIDS epidemic bred difficulty in communication between physicians and their patients. In response to the medical uncertainty, physicians had difficulty deciding to change, especially when the experience of both the physicians and patients was based on the success of AHF concentrate (Aledort, Dietrich, Levine, Lusher interviews). For example, several physicians reported that patients and families resisted MASAC's cryoprecipitate option if they had experience with AHF concentrate. But some individuals with hemophilia believed that single donor cryoprecipitate was a way to buy time (see Case Study Two). In several instances, physicians or patients who contacted the American Red Cross to obtain cryoprecipitate were told that it was not available (see Case Study Two; Dietrich, Louvrein interviews). But even when cryoprecipitate was available, patients were resistant to using it (Dietrich, Lusher interviews). Patients and their families seemed unwilling to "go back" to the previous era of dependence on cryoprecipitate (Aledort, Dietrich, Kasper, Levine, Lusher interviews). Patients and physicians both seemed to want to maintain the status quo, perhaps believing that in the face of uncertainty, the best option was inaction.

Conclusions

In its analysis of risk communication, the Committee sought to identify the clinical options that would have reduced the risk of AIDS and to understand what information was actually communicated to patients. In those instances in which information seems not to have been communicated, the Committee explored the institutional, social, and cultural obstacles to communication. The Committee drew the following conclusions:

  • Individuals who were dependent on blood and blood products during the AIDS epidemic faced difficult decisions and desperately needed information.
    Physicians and patients who had become accustomed to making few decisions suddenly found themselves in complex clinical situations in which the risks and benefits of treatment were now uncertain. Restricting or abandoning the use of blood and blood products could lead to increased mortality and morbidity. On the other hand, continued use of these products apparently increased the risk of AIDS.
  • The NHF stepped into a critical communication role.

As often happens in times of intense scientific and medical uncertainty, communication to individuals with hemophilia and to transfusion recipients about the use of blood and blood products was limited in the early years of the epidemic. The NHF acted during these years as an intermediary between federal agencies and the hemophilia community. There was no single government agency responsible for providing information about the risks associated with blood products directly to the consumers of those services. The NHF was able to do this because it was the only national organization with the expertise (through MASAC) in treating individuals with bleeding disorders.

In contrast to the situation for hemophiliacs, no organization stepped forward to communicate the risks of blood transfusions to potential recipients. Many blood bank officials during this period publicly denied that there were any significant risks of AIDS to blood recipients. In this context, because many transfusions occurred on an emergency basis, patients were often not apprised of the growing concerns about the contamination of the blood supply. For both individuals with hemophilia and transfusion recipients, concern that they might refuse care deemed a "medical necessity" further contributed to failures to apprise them fully of the risks.

  • There were many clinical options for responding to the potential risk, but patients did not actively consider many of them.

The Committee documented that a range of clinical options might, in some instances, have reduced or eliminated dependence on AHF concentrate, thereby reducing the risks of HIV infection in the early years of the AIDS epidemic. While it listed some of these options, the NHF never encouraged thorough discussion of these options by patients with severe hemophilia. Rather, the NHF advocated continued use of AHF concentrates for these patients. While members of MASAC were concerned that alternative treatments were unproven, nonetheless, discussion of full range of options with patients should have occurred.

The dramatic successes in the 1970s of treatment with AHF concentrate provided a context in which it was very difficult to abandon, or radically restrict, use of these products for severe hemophiliacs. In their effort to find the right balance between the risks and benefits of AHF concentrate, the NHF, MASAC, and physicians tended to overweight the known risks (i.e., bleeding due to inadequate treatment) and underweight the risks that were still uncertain (i.e., infection with a new, unidentified infectious agent).

Given that so few hemophiliacs had actually manifested symptoms of AIDS, and with no intuition that AIDS has a long asymptomatic incubation period, many concluded that it would be inappropriate to "overreact" to reports of possible blood-borne transmission of the disease. Concerns that patients would respond irrationally to reports of the epidemic led to attempts to "reassure" the hemophiliac community about the use of blood products.

  • The NHF had serious institutional shortcomings as it tried to assume its self-designated role as the source of information about AIDS and its treatment options. These included inadequate resources and experience; possible conflicts of interest problems; and a generally paternalistic communication style that did not accommodate itself to the uncertainties and complexities attendant upon the emergence of AIDS.

Institutional barriers to patient-physician communications and complex relationships between relevant organizations impeded the flow of information. If the NHF had received input from a wider group of experts and consumers, it might have communicated a more explicit and systematic list of clinical options. In addition, in the Committee's opinion, financial and other relationships between the NHF and the blood products industry presented a conflict of interest that ultimately compromised the perceived independence and credibility of NHF's recommendations.

The NHF undertook a mission that now clearly corresponds to the task of advising patients and physicians about the benefits and risks associated with alternative treatment options. The NHF mission was to give treatment advice, but the advice was conclusory. It was offered without discussion of the range of options, the benefits and risks associated with each option, the medical or scientific rationales for its conclusions, or the areas in which uncertainty or scientific disagreement existed. Given the level of uncertainty engendered by the early years of the epidemic, the NHF should have more fully appraised its constituents of the process and logic of its recommendations, and should have done more at an earlier date to publish information patients and physicians might have used in only their assessments and decisions.

  • There were serious social and cultural obstacles to communicating clinical options to reduce the risk of HIV infection for users of blood and blood products. These include the inability of some physicians to accept the implications and their preference for the status quo; misplaced confidence in AHF concentrate; a context in which some severe risks were medically acceptable; and the difficulty of talking about a dire prognosis and communicating uncertainty.

Physicians tended to not discuss all clinical options since their relative merits were so difficult to evaluate in the context of the powerful uncertainties of the AIDS epidemic. During this period, the knowledge base of AIDS was changing rapidly. Buffeted by news and rumor, with no consistent sources of information, many physicians opted to maintain the status quo in their treatment recommendations. In the Committee's view, once the NHF and physicians embarked on a course in which disclosure was constrained, it became much more difficult to move toward disclosure of risk. As physicians began to recognize that many hemophiliacs were infected, the difficulty of discussing the dire implications of the epidemic also compromised candid discussion between patients and physicians.

In addition, the Committee found that the NHF did not perceive the need to let the patients themselves decide matters that were far too complex for simple recommendations. The prevailing assumptions in the hemophilia community about the medically acceptable risks of hepatitis virus infection led to complacency and failure to react to reports of a new infectious risk with sufficient concern. Paternalistic assumptions about medical decisionmaking led to failures to adequately disclose the risks of continuing to use AHF concentrate and enable individuals to make informed decisions for themselves. Failures to develop opportunities for communicating the possibility of widespread infection in the hemophiliac community led to ancillary failures to warn possibly infected individuals of the risks they might pose to others through sexual contact.

  • These obstacles resulted in poor communication of information.

The Committee believes that the need for communication of information actually increased as the dimensions of the epidemic became more apparent. Medical uncertainty increases the need for communication of information about risks associated with blood and blood products and risk reduction options.

  • Better recognition of obstacles to communication of options and a deeper commitment to present patients with a range of possible clinical options might have reduced the powerful sense of betrayal and guilt experienced by many hemophilia patients and their families.

In instances of great uncertainty, it becomes more important for patients to become active participants in the evaluation of the risks and benefits of alternative treatments. Active participation requires knowledge of options. The failure to adequately and fully communicate these options led to a powerful sense of betrayal that exacerbated the tragedy of the epidemic for many patients and their families.

  • The Committee concluded that there were serious shortcomings in effective communication of risks associated with the use of blood and blood products.

Uncertain circumstances warrant increased communication of information about risks associated with blood and blood products and risk-reduction options. As often happens in times of intense scientific and medical uncertainty, communication about risks, benefits, and clinical options was limited.

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Copyright 1995 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK232408

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