Advisory Committee on Human Radiation Experiments Minutes of Meeting of May 8-10, 1995 Monday, May 8, 1995 Attending: Ruth Faden, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Mary Ann Stevenson, Duncan Thomas. Philip Caplan, Special Assistant to the President for Cabinet Affairs, opened the meeting at 9 a.m. Monday, May 8, 1995, in the Terrace Room of the Doubletree Park Terrace Hotel, 1515 Rhode Island Avenue NW, Washington, D.C. Dr. Faden briefed members on the agenda. She said Administration officials had indicated to her that there is no objection to extending the Committee's charter through the summer, although official notice has not yet been received. Approval of Minutes Members approved the minutes of the meeting of April 10-12, 1995, as presented. Public Comment Mrs. Barbara Tatterson, Cincinnati, Ohio. Mrs. Tatterson spoke on behalf of her late cousin, David Jungnickel, a subject in the Cincinnati General Hospital experiments involving total- body irradiation (TBI). Mr. Clifford Tidwell, Cincinnati, Ohio. Mr. Tidwell spoke on behalf of the Tidwell family about James Tidwell, a subject in the Cincinnati TBI experiments. He said Mr. Tidwell was a subject without consent, and died in great pain because of unauthorized interventions as part of the research. Beatrice Tidwell Green, Cincinnati, Ohio. The daughter of James Tidwell spoke about the trauma to the family caused by Mr. Tidwell's death. Doris Baker, Cincinnati, Ohio. Mrs. Baker read into the record a statement from Betty Smith about Lily Wright, her mother, a subject in the Cincinnati TBI experiments in 1965-66. She said there was no consent for experimentation and Mrs. Wright suffered great pain. Mrs. Baker then spoke on behalf of Cincinnati Families of Radiation Victims Organization and her great-grandmother, Gertrude Newell, a Cincinnati TBI subject. Dr. Katz asked Mrs. Baker to provide recommendations for the Advisory Committee. In addition to full disclosure about the TBI experiments and punishment for those responsible, Mrs. Baker said that families need assistance in interpreting medical records and counseling for families. Patricia Broudy, Monarch Beach, California. Mrs. Broudy presented documents about destruction of film badges and other records which might have documented radiation exposures to soldiers and sailors at atomic weapons tests. She also presented documents about the exposures of downwind populations, especially the town of St. George, Utah, and in shot Harry of the Upshot- Knothole test series. She said that the Task Force on Radiation and Human Rights asks that the Advisory Committee recommend that Congress waive sovereign immunity defenses against lawsuits in cases where experiments are found to be ethically questionable. Gwendon Plair, Washington, D.C. Dr. Plair spoke on behalf of his family about the pain suffered by his mother, Beatrice Plair, a Cincinnati TBI subject who died in 1965. Dr. Plair said his mother was given pain medication only after pleading to hospital staff. He presented a statement on behalf of the Task Force on Radiation and Human Rights, requesting an additional field hearing in the northeastern United States and suggesting remedies for consideration by the Advisory Committee. Committee Discussion: Overall Report Structure. Ruth Faden Members discussed the overall organization and structure of the draft Final Report. Several members said flowery language may detract from the power of straightforward conclusions drawn from the evidence. Several members suggested that a shorter report would be more persuasive to policymakers in charge of future research efforts. Professor King and Dr. Royal suggested that case studies include a justification for selecting these experiments for in- depth attention. Dr. Royal said it's important to indicate which experiments are troublesome ethically and why that is the case. Committee Discussion: Part I of Draft Final Report. Jonathan Moreno. Dr. Moreno briefed members on changes to Part I, Chapter 5: "Ethics Standards in Retrospect." Members discussed how to assess the ethical standards described in government documents. Drs. King, Katz and Stevenson suggested that the word "policy" may overestimate the thoroughness and operative effectiveness of the various government statements cited in Part I. Dr. Moreno suggested that the documents suggest at least a minimal level of commitment to issues like informed consent for healthy subjects. Members agreed to rephrase the description to reflect the ambiguities in government documents dealing with consent issues. Members agreed that widespread consent requirements for sick patients evolved over time, with the earliest concerns focused on unusually hazardous interventions. Members agreed to modify language describing risk-assessment uncertainties in policies relating to distribution of radioisotopes by the Atomic Energy Commission. Members discussed the historical roots of informed consent for healthy subjects, particularly in the traditions of infectious disease research and Committee on Medical Research policies in World War II. Members also discussed assessments of culpability of the medical professions. Members generally agreed with the draft descriptions of differing standard applied to research on healthy subjects, or on patients. Members discussed the application of standards to therapeutic and non-therapeutic research, without consent, in the 1940s and 1950s. The staff draft said non-therapeutic research without consent was wrong and researchers were at least in part blameworthy for allowing that process to continue. Several members expressed little philosophical difficulty with the chapter draft, with Dr. Oleinick noting that consent practices with healthy subjects were so well-established that it is not a large leap to saying patients should have had at least the same consideration. Dr. Russell said that the chapter need not answer all the questions it raises, with the decision depending on the evidence available. Physicians working with healthy subjects clearly knew they were outside the bounds of the doctor-patient relationship; physician-investigators conducting non-therapeutic research should have known the same thing with patients, and could be held blameworthy, he said. Dr. Thomas recommended that a chapter or section of a chapter on moral implications of mass exposures might have to be added to Part I. Tuesday, May 9, 1995 Attending: Ruth Faden, Kenneth Feinberg, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Mary Ann Stevenson, Philip Russell, Duncan Thomas. Committee Discussion: Part II, Chapter 1 of the Draft Report (Biodistribution). Members discussed the evidence about consent or lack thereof in the plutonium injection cases. Dr. Royal said it is clear that consent should have been obtained, but questioned whether the Committee has enough evidence to make a judgement. Members debated the conclusion in the draft that patients were not told that they were in a research project, and that the work was not done for patient benefit. Dr. Royal noted that patients at Rochester were moved to a special unit, there were an unusual number of tests done and samples taken, and there was no incentive to hide the research in some cases. Dr. Faden said the Committee must draw inferences, or not, based on what evidence can be obtained. The evidence is circumstantial, but Dr. Faden said it seems enough to establish that consent was not obtained. Dr. Russell noted the harms arising from secrecy, although Dr. Royal noted that at least in one San Francisco case, the study with Simeon Shaw, the experiment was widely publicized. Dr. Oleinick said it is not likely that every case was handled exactly the same, but the lack of adequate disclosure can be demonstrated from even limited evidence. Dr. Faden said there appears to be agreement among most members that evidence suggests, with important differences among sets of injections, that subjects were not told that they were subjects in research that was not intended to benefit them. Dr. Katz suggested that the roar of the lion in the evidence would be the squeak of a mouse if the chapter does not make a strong statement about the inadequacy of consent procedures in medical research generally at the time. Members discussed how to describe historical wrongs in the Final Report. Committee Discussion: Part II, Chapter 3 (Children and Pregnant Women). Members discussed risk estimates cited in the chapter draft. Dr. Faden asked that members with technical expertise study and report on the cases most likely to require notification and medical followup. Members discussed the chapter's treatment of risk and subject selection. Dr. Faden suggested that the Committee concentrate its attention on non-therapeutic research with children, but members also noted the need to make some statement on nasopharyngeal irradiation studies. The subcommittee on risk analysis was asked to report in particular on the risk and notification issues surrounding nasopharyngeal studies of Navy submariners as well as children. Committee Discussion: Part I, Chapter 5 (Ethics Standards in Retrospect). Jonathan Moreno, Valerie Hurt. Dr. Moreno briefed members on revised characterizations of government ethics standards or policies in the period 1944-74. Members discussed the understanding of officials setting rules for "normal volunteers" in the 1940s and 1950s and the differences in ways that patient-subjects were treated, as well as the evolution of consent and peer review standards at the National Institutes of Health Clinical Center. Members discussed the ethical basis for retrospective moral judgements, particularly in cases where officials failed to hold their subordinates accountable for articulated ethical standards; and also in cases where the absence of standards complicates the assessment of culpability. Committee Discussion: Subject Interview Study. Jeremy Sugarman, Nancy Kass, Monica Schoch-Spana, Patricia Perentesis. Dr. Sugarman briefed members on the subject interview study. He reported that staff have not yet completed its analysis on respondents who wrongly believed they were or were not participants in research. Members asked about information gleaned about physician- subject relations and the reasons persons agreed to be subjects. Members generally approved of the progress of the draft chapter on the subject interview study. Committee Discussion: Research Proposal Review Project. Gail Geller, Shobita Parthasarathy. Dr. Geller and Ms. Parthasarathy reported on the progress of the research proposal review project. Members suggested changes in the analysis of the reviews, including standards for matching the formal reviews by the entire Committee with the independent analysis performed by Dr. Katz. Members suggested changes in the characterization of some studies, particularly those involving complex and not easily explained issues of risks and benefits. Members asked that the draft make clear that the problematic ratings of studies were generally tied to communication, but Dr. Faden cautioned members that some studies involving persons of questionable competence are still under review by staff, and those studies raise different-order concerns. Dr. Katz said the analysis of protocol reviews is intended to check the efficacy of the existing institutional review board (IRB) process, but Dr. Macklin said the review can provide only inferences, because the review project does not involve all the communications -- IRB minutes, revisions to forms etc. -- that are part of the IRB process. Dr. Royal said the project does demonstrate a striking difference in approach among IRBs from a variety of institutions. He said the lack of clarity in consent forms, which are the subject of at least some thoughtful consideration on the part of investigators, may suggest that things don't get any clearer for the subject when oral briefings are conducted by investigators or primary-care physicians. Dr. Glatstein said the process is very dependent on the varying levels of effectiveness of local IRBs. Dr. Faden noted that a number of reviews, including some by Dr. Katz, found examples of outstanding consent forms, showing that improvements in the process are possible. Dr. Russell said he favored defining ways to make today's system work better, rather than replacing today's system with another system that will share the ills to which fallible humans are heir. Dr. Macklin, however, suggested that local ethical judgements may not be effective in dealing with the problems and Dr. Katz said radical reforms are needed. Dr. Oleinick asked that comments and suggestions from IRB chairs should be included in the draft chapter. Wednesday, May 10, 1995 Attending: Ruth Faden, Kenneth Feinberg, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Duncan Thomas. Committee Discussion: Strategy and Direction. Ruth Faden. Members discussed strategies and direction for the remaining time available to the Committee. Dr. Katz said that the review of protocols shows major ethical problems with approved studies across the country, and that the Committee's efforts to date have not adequately addressed this important issue. He urged that members regroup and address these issues in more detail. Dr. Royal said that biomedical research chapters in the Final Report need more attention to ethical issues. Dr. Katz suggested that additional resources be applied to the contemporary projects on an urgent basis, but other members suggested that a detailed analysis of the data already collected for the contemporary projects may yield much more useful information than is presently available to the Committee. Dr. Faden said the contemporary projects are still under way, and it is premature to assess their full utility until the findings are developed. Members discussed the status of the draft Final Report. Professor King said the Committee needs to focus on key chapters, removing from the Final Report those of lower priority and developing them for the companion volumes. Dr. Thomas said that no chapters should be dropped. Dr. Oleinick agreed that the observational studies chapter is a strong addition to the report, but that portions of some chapters can be deleted in the interest of time. Dr. Royal said a priority should be biomedical experiments. Dr. Stevenson said priorities might mean failing to address all the major categories of cases of concern to the public. Dr. Lederer said the report is too long, overwhelming readers with detail, however important the story. Dr. Macklin said it is important to respond to concerns the public has brought to the Committee. Dr. Royal said there should be chapters directed to the public about the risks and benefits of research, e.g. difficulties of proving causality in radiogenic diseases. Dr. Faden polled members on which chapters are in good shape and which need much additional work. Members generally liked Part I, but suggested the trimming of some parts of Chapter 5. Part II chapters were discussed individually. Members generally suggested reducing lengths of chapters, with attention focusing on chapters needing more work, especially pregnant women and children. Suggestions included rearranging or redistributing the Chapter 3 material in other places. Members said TBI and biodistribution are priority chapters, with the need for some condensing of material. Prisoners (Chapter 5) was felt to be in good shape, but where it fit provoked a range of suggestions, from using it in a companion volume or combining it with treatments of institutionalized populations. Members discussed chapters dealing with mass exposures and observational studies, urging more work in particular on Chapter 6, covering experiments in connection with atomic weapons tests. Committee Discussion: Strategy and Direction. Anna Mastroianni. Ms. Mastroianni distributed a draft work plan for the summer months. Members discussed schedules and staff availability, and how many more Committee meetings are necessary. Members agreed to meet in June, focusing on parts III and IV of the final report, with a final draft before the Committee in a July meeting. Members agreed to identify chapters on which they can offer special time or expertise to the revisions of Part II chapters. Members were asked to flag chapter drafts with which they have specific disagreements, so that staff can work with members on critical areas. Dr. Thomas said it is important that staff notify members when substantive changes suggested by members are not adopted. Professor King said that members must be consulted on disagreements among two or more Committee members. Mr. Feinberg said full Committee time should be limited to policy issues that rise to the level of major problems. Members agreed that extensive outside review of the entire report is impractical in light of time constraints, but that members would solicit comments on an informal basis, as individuals. Mr. Guttman noted that chapter drafts are being made available to the public in the Committee's public reading room in Washington. Committee Discussion: Part IV of Final Report (Recommendations). Members discussed the four situations which represent principles for remedies. Members suggested changes, especially in the rationales for specific sets of remedies. Professor King said the Situation 1-A (no harm, apology) phraseology will provoke a personal dissent unless it conveys regret without necessarily condemning government actions that may have been felt to be right at the time. Members agreed to more descriptive than prescriptive language. Members questioned whether any cases in fact meet the rationale of Situation 2-A (non-therapeutic research in which subjects were harmed). Dr. Faden said the Committee's research has identified several candidate cases. However, whether these cases actually fit the Situation 2-A pattern requires fact finding on a subject by subject basis, which is beyond the capacity of the Advisory Committee. Members noted that some cases, e.g., prisoner experiments in Oregon and Washington or some experiments involving children, may fall under the Situation 2-A principle. Mr. Feinberg said implementation should be left to agencies or Congress. Members suggested refinements in the language. Members discussed Situation 2-B (therapeutic research in which subjects were harmed) provides reimbursement for medical expenses for net harms caused by therapeutic research. Members noted that both causation and the assessment of net medical harms can be very difficult. Mr. Feinberg suggested a refined version of 2-B requiring an apology as remedy. Dr. Thomas added that it should include compensation if the subjects were harmed as a result of their exposure, and where subjects were not adequately informed of risks. Dr. Macklin said the important missing element in the draft is the suspicion that dual-purpose experiments were done for a government purpose, and otherwise probably would not have been done. Dr. Faden said the 2-A language can be softened to encompass the possibility that therapeutic intent may be dubious. Dr. Faden said a separate set of recommendations would be drafted for mass exposures. Mr. Guttman, as the designated federal official, closed the meeting at 4 p.m.