Advisory Committee on Human Radiation Experiments Meeting of July 17-19, 1995 Monday, July 17, 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 and Deputy staff secretary, opened the meeting at the Executive Chambers, Madison Hotel, 15th and M Streets NW, Washington, D.C. Dr. Faden briefed members on the agenda. Public Comment Minister of Foreign Affairs Philip Muller, Senator Tony de Brum, Ambassadors Larry Edwards and Wilfred Kendall, Republic of the Marshall Islands. Foreign Minister Muller thanked the Committee for its work in developing information important to the Marshall Islands. Senator de Brum commented on the draft chapter of the final report dealing with fallout exposures and subsequent medical treatment and research in the Marshall Islands. Bernard Aron, M.D., Cincinnati, Ohio. Dr. Aron, an oncologist, described his work with total-body irradiation patients at Cincinnati General Hospital. Members questioned Dr. Aron about subject selection, general use of radiation therapies at the hospital, and Department of Defense and Public Health Service funding for the studies. David Egilman, M.D., Braintree, Mass. Dr. Egilman commented on the draft chapter on total-body irradiation. Oscar Rosen, Boston, Mass. Dr. Rosen of the National Association of Atomic Veterans commented on recommendations for remedies for participants in atomic weapons tests. Dennis Nelson, Bethesda, Md. Dr. Nelson briefed members on additional materials regarding fallout exposures to citizens living near the Nevada Test Site. Mary Claire Mueller, Washington, D.C. Ms. Mueller described her experience with radiation treatments and her difficulty in obtaining relevant records. Acie Byrd, Cincinnati, Ohio. Mr. Byrd presented a statement on behalf of the Task Force on Radiation and Human Rights, citing accomplishments of the Committee but urging additional steps to respond to concerns of experiment subjects and their families. Committee Discussion: Chapters in Part I and Part II Dr. Faden asked members to identify chapters that needed discussion by the full Committee. Dr. Katz and Professor King expressed concern about the substantial weight laid in Part I on the interpretation of documents such as the Nuremberg Code and Defense Secretary Wilson's 1953 directive adopting the code for DOD research. Members suggested changes to the children's chapter relating to risk assessment, consent, the rationale for medical follow-up, and the suitability of today's regulations on risk. Members discussed where to locate in the report a discussion of the nasopharyngeal studies of children and military personnel. Members agreed to include a discussion of the nasopharyngeal studies as a box in the chapter. Members discussed how to communicate radiation risks in both the intentional release chapter and the rest of the report. Dr. Thomas suggested that the context of risk assessment could be added to a proposed box on risk being developed elsewhere in the report. Members suggested changes to the atomic weapons testing chapter to define experimental activities precisely and identify problems with military recordkeeping policies. Members suggested changes to the chapter on plutonium injections and related experiments. Members asked for clearer descriptions of available evidence, particularly about consent issues related to the experiments, and a more precise definition of harms resulting from exposures. Members agreed that information about Boston and Rochester uranium injections should not be separated from the main text in a box. Dr. Faden said staff was reviewing pathology reports from uranium injection experiments to determine whether clinical harms resulted from those studies. Members suggested changes to the observational studies chapter, including reconsideration of material on researchers' obligations to warn uranium miners under study. Committee Discussion: Findings, 1944-74 Members deferred discussion of Finding 11-C, assessing the blameworthiness of experiments in which inadequate consent appears tohave been obtained, until members could also address Part I, Chapter 4, the analysis of ethics policies. Finding 16 (regarding Marshall Islands exposures) was deferred until Committee review of a revised chapter draft. Tuesday, July18, 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, Reed Tuckson. Committee Discussion: Recommendations on Remedies for Former Subjects. Members discussed recommendations about remedies for former subjects in the period 1944-74. Members agreed to defer until Wednesday's discussion of the total-body irradiation chapter a consideration of issues arising from Recommendation 2, involving questionable therapeutic rationales resulting in harm to subjects. Professor King suggested that recommendations not include headlines or titles, because cryptic headlines might be misleading. Dr. Royal asked that staff look into ways to make the texts of key documents available in the final report. Members discussed the appropriateness of an apology to subjects apparently unharmed by experimentation, but likely to have been recruited through inadequate consent processes. Members discussed the recommendations regarding apologies, and asked that Dr. Faden express the tone of the Committee's concerns in her letter of transmittal to the President. Members discussed Recommendation 3, agreeing on the outrage and regret felt about some cases in which people were used as research subjects without any prospect of benefits, but noting the grave evidentiary difficulties in many cases. Dr. Faden agreed to consult with absent members but suggested that if the consensus is to delete Recommendation 3 that additional language in the preface or in chapters about specific cases may meet the concerns of members who wished to include an apology recommendation for specific cases. Committee Discussion: Research Proposal Review Project. (RPRP) Members discussed IRB review of the scientific merit of research proposals, and instances in which basic ethical principles were unaddressed in protocols. Members suggested editing changes to integrate Dr. Katz' independent review of protocols into the RPRP chapter. Committee Discussion: Subject Interview Study (SIS) Members discussed the subject interview chapter and suggested editing changes, particularly focusing on making clear the percentages in the surveys and avoiding misrepresentation of the significance of the report. Committee Discussion: Contemporary Projects -- An Ethical Analysis Dr. Kahn briefed members on the new draft chapter (Part III, Chapter 17) to combine the ethical analysis of the RPRP and SIS chapters. Committee Discussion: Findings relating to the contemporary world Members reviewed findings relevant to the contemporary world and suggested changes. In Finding 21, members agreed to note that the contemporary projects found no meaningful ethical differences between radiation and nonradiation human subjects research. Members agreed to note that radiation research is subject to more regulation than nonradiation research. Members agreed to add a finding designed to address public confusion about the difference between research and application of innovative therapies. Committee Discussion: Recommendations for the Protection of the Rights and Interests of Human Subjects Members agreed to delete a proposed general recommendation about public education, but at the suggestion of Drs. Tuckson and Glatstein, references to public education about the risks and benefits of research were to be added at appropriate places in the text. Members suggested that Recommendation 11 be separated into four specific recommendations regarding changes to today's federal regulatory scheme for the protection of human subjects. Dr. Katz proposed adding a fifth recommendation, a general review of the Common Rule governing human subject research in the federal government. Members discussed and suggested changes in the recommendation dealing with the financial implications for subjects of participation in research. Dr. Royal suggested noting the bureaucratic burden to IRBs of reviewing the growing percentage of protocols that, in an era of declining research budgets, end up not being funded. Committee Discussion: Recommendations for Balancing National Security Interests and the Rights of the Public Members discussed and suggested changes to recommendations dealing with regulation of classified research and the regulation of intentional releases conducted in classified programs by the government. Issues included the "triggers" of review of releases under existing environmental laws, and the need to reassure the public about intentional releases, even where risk is minimal Members discussed recommendations relating to openness and preservation of critical records about research. Dr. Lederer was asked to redraft part of those recommendations for consideration at Wednesday's meeting. Members discussed the bureaucratic burdens of implementation of the recommendations and suggested changes to the texts. Members directed the staff to assess later whether a recommendation is needed urging the National Archives to create a specific repository Advisory Committee records. The recommendation may be deleted from the final report if it has already been substantially accomplished by the time of the preparation of the final report. Committee Discussion: Recommendations related to population exposures Members discussed Recommendations 6, 7, and 8, regarding population exposures, and suggested changes. Key issues included whether parts of the recommendations would overlap the ongoing Institute of Medicine assesment of exposures to troops at weapons tests. Members discussed how best to represent to the government the concerns of veterans and downwinders who have sharply criticized existing government compensation schemes. Wednesday, July 19, 1995 Attending: Ruth Faden, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin (via telephone), Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Mary Ann Stevenson, Duncan Thomas, Reed Tuckson. Approval of Minutes The minutes of the June 1995 meeting of the Committee were approved without changes. Committee Discussion: Strategy and Direction. Dr. Faden briefed members on the agenda and noted that Dr. Macklin would contribute to the meeting via speakerphone. Dr. Faden asked members to share their views about individual statements contemplated for submission into the final report. Professor King said that if she prepared a statement, it would address the appropriateness of some of the retrospective moral judgments in the final report, particularly in Chapter 4 (Ethics Standards in Retrospect), and some of the findings and recommendations. Dr. Katz said that if he contributed a statement, it would focus on inadequacies in today's system of research oversight and in the Committee's recommendations for protecting the rights and interests of human subjects. Dr. Royal said that if he made a statement, it would address his discomfort with the evidentiary base from which many judgments are adduced in the final report. Dr. Faden said she might contribute a statement to acknowledge the contributions of those who worked to produce the report. Committee Discussion: Total Body Irradiation Members discussed the chapter on total-body irradiation and suggested changes to the chapter. Members agreed how to characterize the Defense Department's rationales for funding TBI studies. Members also agreed to include material in the chapter on subject selection and competence of some subjects to consent to the Cincinnati TBI experiments. Members discussed the conclusions of the TBI chapter and suggested changes, particularly in bulleted material. Issues included descriptions of the military's motives in sponsoring different TBI studies; consent or lack thereof in the Cincinnati case; ethical issues in multipurpose research projects; and the palliative treatments afforded patient-subjects in the Cincinnati study. Committee Discussion: Ethics Standards in Retrospect Members discussed the ethics framework outlined in Part I, Chapter 4, and the related finding (11-C) regarding evaluation of past experiments. Members directed the staff to redraft the chapter to include more detailed frameworks for moral analysis. Dr. Faden asked that members make the draft a priority for returning their comments. Committee Discussion: Medical Notification and Follow-up Members discussed Recommendation 4, regarding medical notification and followup (Part IV, Chapter 19) and suggested changes. Drs. Thomas and Royal pointed out the difficulties of assessing risks and recommending appropriate follow-up. Dr. Tuckson outlined the public-health issues involved in notification. Dr. Faden said language would be developed to explain trade- offs between risks and benefits to portray for surviving subjects the uncertainties of risk and responses. Committee Discussion: Openness Members discussed Recommendation 15 as redrafted by Dr. Lederer, that conflated the previously considered Recommendations 15 and 16 on access to information about experimentation. Members approved it with some changes. Committee Discussion: Findings (Risks of Harm) Members discussed a revision by Dr. Thomas of Finding 2, regarding risks of harm. Members agreed to the new language, with some changes to more precisely describe the risks from tracer studies. Committee Discussion: Recommendations (Epidemiological Study and Atomic Veterans) Members discussed a revised recommendation from Dr. Thomas about epidemiological study of veterans involved in experimentation in connection with atomic weapons tests. Members agreed to the recommendation language with some changes, and directed the staff to incorporate some of that language in the relevant chapter of the report rather than the recommendations chapter. Committee Discussion: Recommendations (Monitoring, Oversight and Sanctions) Members discussed the draft Recommendation 11d, regarding prospective monitoring and oversight of human subjects research, and sanctions against ethical transgressions. Members recommended changes in the recommendation in areas of oversight staffing and in sanctions. Committee Discussion: Observational Studies Members discussed and made suggestions for the Marshall Islands portion of the chapter on observational studies, and the concomitant Finding 16 and Recommendation 9. Professor King suggested that some of the concerns might be communicated to appropriate federal officials by letter from the Advisory Committee chair. Members questioned Mr. Klaidman about evidence available relative to the concerns raised by the Marshall Islands delegation in the July 17 public comment period. Dr. Thomas suggested that the references in Finding 16 to deaths of uranium miners should be supplemented with mention of the health effects of exposures in the Marshalls, including the death of a Japanese fisherman on the Lucky Dragon exposed by the 1954 Bravo detonation. Members agreed that the finding should reflect those issues. Members agreed that parts of the Marshallese recommendation and others that involve passing on of concerns drawn from public testimony should be transmitted by the Committee to appropriate federal authorities. Dr. Faden said she would try to make these recommendations consistent, with pass-along issues either being mentioned in the report, or expressed by letter to federal agencies, or both. Committee Discussion: Strategy and Direction Dr. Oleinick requested that members see the findings and recommendations in one document without explanatory text as soon as possible, to provide members with an overview of all of the recommendations. Dr. Faden briefed members on the schedule of drafts to be sent in July and August. Mr. Caplan closed the meeting and expressed thanks to members for the service on the Advisory Committee.