Advisory Committee on Human Radiation Experiments Minutes of Meeting of March 15-17, 1995 Wednesday, March 15, 1995 Attending: Ruth Faden, Kenneth Feinberg, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Duncan Thomas, Reed Tuckson. Philip Caplan, Special Assistant to the President for Cabinet Affairs, officially opened the meeting. Dr. Faden briefed members on the agenda for the twelfth meeting of the Advisory Committee. Approval of Minutes Members approved without change the minutes of the February 15-17, 1995, meeting of the Advisory Committee. Public Comment Ernest Sternglass, Pittsburgh, Pennsylvania. Dr. Sternglass discussed radiation doses and health effects, particularly what he called serious health effects of low-dose exposures from fallout and other intentional releases of radioactivity. He said the impact of chronic low-dose exposures should be considered in the Committee s discussion of remedies. Dr. Sternglass urged that the Committee recommend an independent reassessment of a 1990 National Cancer Institute study of radiation dangers to residents of counties surrounding nuclear production facilities. Dr. Oleinick questioned Dr. Sternglass about his correlation of low birth weights to strontium-90 contamination. Elmerine Whitfield Bell, Dallas, Texas. Mrs. Bell, daughter of Elmer Allen (CAL-3), a subject in the University of California, San Francisco plutonium injections, spoke about her father and her family s experience living with the effects of his poor health. She also presented written testimony from her daughter about Mr. Allen s life. Mrs. Bell said her father was not properly informed nor did he give proper consent to plutonium injections, and she urged members to look critically at the UCSF committee report on the injections. Cooper Brown, Takoma Park, Maryland. Mr. Brown, of the Task Force on Radiation and Human Rights, presented a paper on principles the task force believes should guide remedies recommendations of the Advisory Committee. Dr. Oscar Rosen, Boston, Massachusetts. Dr. Rosen, commander of the National Association of Atomic Veterans, praised the work of the Committee in making the documentary record available to citizens. He also praised the Committee s disclosure of the experimental nature of fallout studies in Operation Jangle of 1951. Dr. Rosen urged members to address a wide range of issues of importance to veterans exposed in nuclear weapons testing. Glenn Alcalay, New York, New York. Mr. Alcalay spoke about his work since 1975 with women of Utirik, an atoll in the Marshall Islands exposed to fallout during weapons testing. He criticized Brookhaven fallout studies for failing to assess the impact of radiation on fertility and birth outcomes in the Marshalls. He urged the Committee to recommend an epidemiological study of women in the Marshalls. Denise Nelson, Bethesda, Maryland. Mrs. Nelson spoke about premature deaths to downwinders from the Nevada Test Site and analogized their exposures to Nazi atrocities. She said the Radiation Exposure Compensation Act has not resulted in justice to downwinders, as many families medical expenses have far outstripped compensation payments. Chris DeNicola, Valerie Wolf and Claudia Mullen, of New Orleans, Louisiana. Ms. Wolf said research subjects had been victimized as children in mind-control experiments, some of them involving radiation and torture. She said her clients in therapy, including Ms. DeNicola and Ms. Mullen, recalled similar incidents and suffered similar ailments. She urged the Committee to ensure full disclosure of CIA and military experiments along the lines of MKULTRA, Bluebird and Artichoke. Ms. DeNicola recalled being the subject of torture and exposure to drugs and radiation in Kansas City and Tucson, in 1966-76. She said this was part of an effort to train her as a spy and assassin. Ms. Mullen described a series of exposures to drugs and abuse from age seven in 1957, continuing to 1984. She said the doctors involved were funded through Edgewood Arsenal in Maryland, and that numerous atrocious acts were committed by doctors and government officials. The panel of commenters called for appointment of a new commission to investigate the mind-control experiments. Suzanne Starr, Chimayo, New Mexico. Ms. Starr said that in 1993 she began to recall experiences similar to those reported by Ms. DeNicola and Ms. Mullen. She described being the subject of abusive types of treatments or experiments as a child in Colorado in the 1950s and into the early 1960s. She said she continues to receive program messages urging her to kill herself. She said through therapy that she has found the strength to speak about her recollections. Steven Schwartz, Washington, D.C. Mr. Schwartz, a guest scholar at the Brookings Institution, spoke about the difficulties of tracking down documentation regarding the development and cost of the nuclear weapons complex. He said many records were destroyed and that adequate financial information was not kept by government agencies. He also discussed the difficulties of obtaining information through the Freedom of Information Act (FOIA) process. Update: Knoxville Small Panel Meeting. Nancy Oleinick. Dr. Oleinick briefed members on the Knoxville small panel meeting, held March 2. She noted the number of scientists and physicians who joined subjects and advocates on the list of persons speaking to the panel. Dr. Oleinick said the panel noted the expressions of fear and concern from citizens working or living near Department of Energy facilities; while these exposures may not be delimited in the charter of the Committee, Dr. Oleinick said that the Committee may wish to acknowledge these concerns and urge government agencies to take appropriate action. Dr. Oleinick said that problems of access to information are a continuing theme from public comment participants. She also noted that a number of patients and families expressed their gratitude that Oak Ridge facilities were available for experimental treatments for leukemia and other diseases. Dr. Faden thanked Dr. Oleinick and Dr. Royal for representing the Committee in Knoxville. Committee Discussion: Final Report. Dan Guttman. Mr. Guttman updated members on efforts of the staff to draft chapters for the final report. Anna Mastroianni, staff associate director, briefed members on the schedule for chapter drafts to be reviewed by Committee members. Dr. Royal asked that members receive comments from other members, so that members get the benefit of others observations. At the suggestion of Dr. Katz, the staff was authorized to approve stylistic changes, but was directed to note for members the incorporation or the rejection of substantive suggestions from Committee members. Dr. Thomas and Dr. Macklin questioned the proposed organization of isotope distribution and biodistribution chapters, and Dr. Thomas suggested that the issues might be better organized along lines of therapeutic or diagnostic use and of experimental use that is not of benefit to the patient. Dr. Faden said a difficulty is the relative lack of information on radiotherapies, and Dr. Glatstein added that the Committee could not survey all subjects in the field of radiation. Dr. Thomas said that the reader of the proposed chapters might get the impression that the high toll of problematic research is the only story, without the story being told about the development of radiotherapies and both their costs and ultimate successes. Thursday, March 16, 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, Duncan Thomas, Reed Tuckson. Statement of Senator Wellstone Senator Paul Wellstone of Minnesota addressed the Committee and urged members to investigate thoroughly the concerns of armed services veterans exposed in connection with weapons tests. He recounted the experience of Minnesota veterans who today feel misled and neglected by their government because of health problems they ascribe to exposures in the nuclear tests. He noted the disclosure of fragmentary evidence of secret Veterans Administration files on veterans exposed during weapons testing. The senator informed the Committee of a preliminary study by the National Academy of Sciences that is considering whether it is feasible to do a full-scale medical follow-up study. He added that the Committee s analysis of intentional releases, though predicated on radiation exposures, might well apply to the spraying of zinc cadmium sulfide over many cities, including Minneapolis, as part of dispersal studies for biological and chemical warfare purposes in the 1950s and 1960s. Members questioned Senator Wellstone about the Committee s scope of inquiry regarding exposures to veterans; ethical criteria to judge intentional releases; and eligibility rules in existing radiation exposure compensation laws. Committee Discussion: Introductory Chapters. Ruth Faden. Members discussed staff suggestions for introductory chapters in the Committee s final report. Subjects discussed by members included the treatment of the Nuremberg doctors trials and the Wilson memorandum that flowed from principles promulgated at the Nuremberg trials; the Cold War backdrop for experiments in the United States; the sense of betrayal felt by affected citizens toward their government; the Nuremberg Code as a description of accepted research practices of its time; and the need to capture first principles in introductory sections of the report. Dr. Royal emphasized that members need to make drafting suggestions as early as possible. Dr. Katz suggested that the opening chapter may be the last to be finalized. Dr. Tuckson said that the introductory chapter should lay out the questions the Committee was formed to answer. Professor King said Dr. Tuckson s suggestion should lead the Committee to begin its report with the story of how the Committee was formed in the wake of the 1993 Albuquerque Tribune series. Members discussed the draft Part I, Chapter 2. Subjects discussed included the use of Walt Disney references in the draft; some members suggested starting with the existence of radioactivity since the dawn of time. Professor King said the audience for the final report is the American public, requiring the broadest treatment of the story uncovered by the Committee. Dr. Royal suggested that the final report should be useful to policymakers first of all, as the Committee wants the government and the professions to take steps to avoid mistakes of the past. Dr. Oleinick suggested places where the chapter might note the broader context of useful radioisotope research, and the fact that the vast majority of experiments were on animals. Members suggested small editorial changes to make the chapter more clear, and Mr. Guttman said that timelines will be included in future drafts. Dr. Tuckson said the chapter, including the Walt Disney reference, usefully illustrates how people thought of radiation in periods covered by the report. He said another audience for the report is the large number of veterans and other stakeholders who have appeared before the Committee. Members discussed Chapter 2-A draft, and the question of whether a stand-alone chapter of testimony from public comment participants should be included. Dr. Macklin suggested it should be included as parts of relevant chapters, but Dr. Thomas said that he felt it a powerful statement of pain felt by many citizens. Dr. Glatstein and Professor King said chapter 2-A should be in the report, but perhaps as an appendix rather than as a chapter. Dr. Tuckson suggested that the chapter should include a set of statements representative of all the general categories of concerns addressed in public comment periods. Dr. Faden said the decision on whether to include a separate testimony chapter would be revisited after more chapters are complete. She said it may also be a relevant part of the findings chapter. Committee Discussion: Recommendations. Ruth Faden. Dr. Faden briefed members on plans for a findings chapter that would precede the recommendations of the Committee in the final report. She emphasized that the discussion was intended to elicit from members general areas that should be addressed in the findings, but not to make final conclusions about findings or recommendations flowing from them. Members addressed drafts prepared by the staff. Issues discussed by members included the order and organization of the findings; the need to propose attainable goals and objectives to government agencies; and the need to craft findings relevant to experiments of opportunity and intentional releases, as well as traditional biomedical experiments. Members discussed findings regarding secrecy; linkages of culpability and compensatory recommendations; phrasing recommendations to maintain editorial consistency; the difficulty of matching abstract cases, and appropriate compensation. Members noted the distinctions between cases in which exemplary damages should be paid by the government, and the problems of drawing distinctions with other cases in which harms or wrongs have occurred, but where the historical record may not be clear enough to provide guidance about compensation or other remedies. Dr. Royal also noted that widely varying judgments may be made about risks and benefits of physical harms. Members discussed the difficulties of demonstrating causation, and whether the draft findings inconsistently held that presumptions could be made with respect to informed consent and not made with respect to physical harms. Mr. Feinberg said the draft findings envision a panel of scientists to develop reasonable presumptions. Mr. Feinberg said that if medical presumptions cannot be established, then a general apology might be available to those wronged, but compensation could only be granted to those persons who are victims of government cover-ups. Professor King noted the difficulty for many subjects in demonstrating that they were victims of a government cover-up. Presentation: National Research Council Study, Alaska I-131. Chester M. Pierce. Dr. Chester Pierce, chair of the National Research Council/Institute of Medicine Committee for Evaluation of 1950s Air Force Human Health Testing in Alaska Using Radioisotope Iodine-131, briefed members on the progress of the study. Members questioned Dr. Pierce and Mr. Loren Setlow, director of the NRC/IOM study, about the background and training of the principal investigator and about the investigator's training at Chicago for use of isotopes provided by the Atomic Energy Commission; about consent issues raised by subjects in 1994 hearings before the NRC/IOM panel; about the language and cultural difficulties between native Alaskan subjects and the investigators; and about what the NRC/IOM panel considered generally acceptable medical standards in the 1950s. Committee Discussion: Recommendations. Ruth Faden. Members resumed their discussion of remedies. Mr. Feinberg and Dr. Macklin said issues of justice might guide the Committee s decision about presumptions for the purpose of remedies, but Mr. Feinberg said that it is important that the Committee adopt a scheme that avoids the scientific difficulties of setting either restrictive presumptions or overly generous presumptions that would be too costly and thus unlikely to be adopted by the government. Dr. Glatstein said the intentional releases and other mass exposures should be treated separately, with generous presumptions for medical problems thought to be related to mass exposures. Members revisited the issue of biomedical experiments in the draft findings. Dr. Thomas said the Advisory Committee should recommend that Congress give policy guidance up front to allow scientists to make reasonable judgments of probability of causation of harms. Professor King said that dealing with mass exposure presumptions might obviate discussion about what Mr. Feinberg called fine and potentially invidious distinctions among different types of experiments. Professor King summarized the question: If the Committee concludes that consent was likely not obtained in many cases, then a presumption is created for remedies, without strict standards of causality in scientific terms. Dr. Thomas said there is a tradeoff: with high likelihood of culpability, generous presumptions on causality; with low likelihood of culpability, higher standards for causality. Dr. Katz said that it is important that remedies be readily applicable and should not be subject to more lengthy deliberation before being put into effect. Friday, March 17, 1995 Attending: Ruth Faden, Eli Glatstein, Jay Katz, Patricia King, Susan Lederer, Ruth Macklin, Lois Norris, Nancy Oleinick, Henry Royal, Philip Russell, Duncan Thomas, Reed Tuckson. Staff Report: Subject Interview Study. Jeremy Sugarman, Nancy Kass, Steve Goodman. Dr. Sugarman briefed members on the progress of the subject interview study. He said 16 of 19 IRBs at institutions approached about the study had approved it, and the 16 sites include an equal number of university, veterans and community hospitals, and governmental research institutions. Dr. Kass said 79 in-depth interviews have already been completed, and she outlined plans for compiling and assessing the data. Dr. Faden introduced Dr. Steve Goodman and Ms. Monica Schoch-Spana, who are working on the project. Members questioned the staff about the sorting and quantative analysis of data and initial impressions from the early returns of in-depth interviews. Staff Report: Research Proposal Reviews. Gail Geller, Sara Chandros. Ms. Chandros reported that 59 radiation reviews and two nonradiation reviews were completed and in the database by March 13. She said more than 100 reviews remain to be done to meet the Committee s original goals for the project. Ms.Chandros briefed members on the preliminary findings of the study. She said almost half of the surveys completed have been rated highly, with eight rated as raising serious ethical concerns. The latter generally were proposals involving higher levels of risk, Ms. Chandros said. Members agreed to prioritize the pool of reviews to reach a goal of five studies per cell of the analytical grid, reducing the number of reviews to be done by about 20. Nonradiation comparison studies would be reduced to about 40 as a result. Members will also be paired with staff members as co-reviewers to increase the number of reviews completed. Members also discussed the process of rating studies and how studies are packaged for review. Dr. Katz reported on his review of 50 protocols. Thirty represented minimal or no risk, as in questionnaire-type studies or tracer studies. Dr. Katz said of the 20 involving higher risk, four were handled well. Ten studies would be given low ratings, on the ACHRE scale, ratings of 4 or 5, Dr. Katz said, outlining specific risks that he felt were very poorly dealt with, or entirely left out of, consent forms. Dr. Russell suggested that a problem is the interweaving of risk discussions with other explanations, and Dr. Royal added that few protocols he has seen provide adequate discussion of quality of life issues facing patients. Dr. Royal said the possibility of benefits is also often poorly explained to patients. Dr. Macklin noted the Committee does not have available to it the verbal presentations to IRBs, in cases where the investigator is present for review of protocols. Dr. Macklin said there may be a huge variability in IRB processes, including whether investigators are disdainful of the IRB process, as she has found some to be. Dr. Katz said his conclusion is that, among studies involving more than minimal risk factors, a primary responsibility of IRBs, to review closely the consent process, is not being adequately met 50 percent of the time. Dr. Faden noted that these are all approved projects, currently being conducted across the country. Dr. Katz also noted that the longer consent forms, some of them nine or ten pages, were the most unclear about risk and benefit. Dr. Geller said there may be problems with IRB review, in terms of IRBs being willing to question the scientific merit of a protocol. Dr. Russell said there is often no funding agency or other body to which IRBs could refer protocols that raise questions of scientific merit. Committee Discussion: Forward-looking Recommendations. Ruth Faden. Members discussed in general terms a list of ideas for forward-looking recommendations for the final report. Dr. Macklin said that the recommendations should make clear whether there should be uniform enforcement of ethical standards for research. Achieving uniformity in today's decentralized system may involve changes that will not be popular with some participants in today's system, Dr. Macklin said. Dr. Katz said federal regulations need to be revised radically, and that recommendations directed to IRBs may not be helpful in light of a lack of a national board to oversee the IRB process. Dr. Russell said the search for uniformity across the federal government is likely to bring down the average quality rather than to raise it. He doubted the wisdom of adding another centralized level of bureaucracy. Dr. Faden asked that the staff circulate an article by Dr. Katz on the issue of a national board to oversee human subject research. Mr. Guttman said the recommendations might include suggestions about what a citizen should ask if he/she or a family member is asked to be a study subject. Dr. Glatstein said federal funding should be tied to educational requirements for IRBs, or a national conference for focusing on consent issues. NIH has not been a regulatory agency, he said. Dr. Russell said the bureaucratic workload should be reduced to focus more attention on higher-risk protocols. Dr. Glatstein said that there is an underlying tendency among IRB members to support investigators proposals, particularly when the goal of the study is perceived as particularly valuable. Members discussed the wisdom of adding more lay persons to IRBs. Members generally agreed with addressing in the final report concepts of differentiating research from treatment; better communicating of risk and benefit; and avoiding presumptions of agreement in consent forms. Members also discussed the role of drug companies in funding clinical trials. Dr. Royal said that oversight of research should not be vested in funding agencies, which have a vested interest in funding more research. Consent forms are preserved under existing regulations, and perhaps should be audited or reviewed, he said. Having some feedback about issues of communicating risk and benefit to the patient would provide the most bang for the buck in federal terms, Dr. Royal said. Dr. Glatstein said the National Cancer Institute already reviews consent forms, but he said that a recommendation might include focusing such agencies more on issues of communication with patients. Drs. Russell and Glatstein said regulatory agencies such as the Joint Committee on Accreditation of Hospitals tend to look at whether IRBs exist, but a Committee recommendation might seek more attention on whether they are doing a good job. Members discussed ideas for more education for IRB members on ethical concerns. Dr. Tuckson said that the big picture is that recommendations ought to change govenrment behavior. Professor King said certification of IRB members may not achieve Dr. Tuckson s big-picture goal, and that the responses to these issues must be more than perfunctory on the part of the participants in the medical community; the recommendations must be more than credentialism through certification, but should, perhaps, suggest ways for IRBs to accomplish goals of real communication in the IRB and elsewhere in the system. Dr. Faden said ideas for educational recommendations should be aimed at the widest community of biomedical research. Dr. Royal said the advantage of certification is that people cannot say after the fact that they didn t know the rules. Dr. Macklin concluded that both sides of the certification discussion are correct. Dr. Tuckson said that there needs to be some convening of leadership in American universities and hospitals, to determine how to achieve important ethical goals. Professor King said the IRB enterprise should empower lay members to address ethics issues. Dr. Tuckson said the relevant background material is also important and should be readily available. Members discussed accountability, oversight and sanctions. Members focused on questions of what is practical in a time of declining federal spending, and what actual monitoring of the consent process is done today. Dr. Macklin noted that oversight and monitoring of the consent process is envisioned in today's regulations, but is in fact rarely done. While Dr. Katz suggested that such reviews would be very unpopular with investigators, Dr. Glatstein said that regulations tied to funding will be obeyed. Members asked staff for details about sanctions that might be deployed to improve ethical conduct. Dr. Macklin suggested that IRBs may not be the best mechanism to determine whether sanctions should be invoked. Members moved to a discussion of potential categories of remedies in response to findings about intentional releases and mass exposures. Dr. Glatstein said planned intentional releases or exposures of soldiers should require written authorization from the President of the United States. Dr. Russell noted that civilian authority is already asserted over the military by the service secretaries, who are appointed by and responsible to the President. Dr. Russell also noted that today's armed forces regulations include extensive risk analyses, extending beyond radiation. He suggested addressing recommendations to the interface between training and research activities, and particularly embedding instruction in human research ethics in th education of officers of the U.S. armed forces. Dr. Faden asked the staff to provide a background paper on mechanisms and recommendations regarding waiver of exposure standards. Members also asked for clarification of issues involving medical interventions to protect troops. Members generally approved addressing issues of openness, including preservation of the Advisory Committee document collection for citizen use, and an ombudsman for citizen access to archives on this subject generally. Members asked for detail about a proposed registry of human subject research. Committee Discussion: Retrospective Recommendations and Notification. Ruth Faden. Members discussed the charter requirement that the Committee address the issue of notification of subjects of experimentation. Dr. Faden said the Committee's research into children, prisoners and fetuses exposed to ionizing radiation have been the principal focus of notification requirements. Dr. Thomas has also been asked to consider issues of genetic effects and notification of subsequent generations. Dr. Royal asked that staff further research a suggestion that a notification effort be aimed at potential thyroid cases where exposures suggest 1 in 1,000 chance of abnormalities. Dr. Thomas and Professor King suggested that there are models for inquiring of people whether they would like to know about potential threats, e.g. genetic screening cases. Professor King said issues might involve reproductive health. Dr. Royal said large-dose studies of I-131 have shown no connection with reproductive health. Dr. Royal said the vast increase in efficiency of diagnostic techniques results in more treatment of slow-growing cancers, like thyroid and prostate, which may result in more morbidity because of interventions arising from notifying persons than from leaving well enough alone. Professor King said the critical issue is putting those on a research protocol in the past on the same footing as those today. While there are people who do not want to know, they would have the right to know today, she said. Dr. Tuckson said that the individual should have the opportunity to seek more information, similar to testing for Parkinson s disease genes. Public concern is very great and the issue must be addressed, even if there remain great practical difficulties, Dr. Tuckson said. Dr. Royal said notification is also bound up with the knowledge of the circumstances of the experiment, so that the chance of a reasonable diagnosis and treatment is increased. Dr. Tuckson said that institutions that conducted radiation experiments have a moral obligation to find subjects and notify them. Dr. Macklin said it is a matter of rights, the exercise of which sometimes results in harms. Dr. Faden summarized the discussion: that people have a right to know if they were subjects, and that no barriers should be erected to people finding out. She said the Committee would leave open for the moment the criteria by which institutions should choose which experiments to focus notification efforts. Dr. Thomas added that any program should respect the right not to know of those who do not wish to know. Dr. Faden said the practical problem is finding people. Meeting Update Dr. Faden briefed members on the upcoming meeting schedule. As the designated federal official, Mr. Guttman closed the meeting at 4 p.m.