Compensating for Research Injuries The Ethical and Legal Implications of Programs to Redress Injured Subjects Volume 1. Report (U. S. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Washington, DC Jun 82 U. S. Department of Commerce National Technical Information Service BIBIOGRAPHIC INFORMATION PR83-23694 Compensating for Research Injuries: The Ethical and Legal Implica-tions of Programs to Redress Injured Subjects. Volume 1. Report. Jun 82 PERFORMER: President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Washington, DC. See also Volume 2, PB236802. Also available in sets of 2 reports PC$16.00, PB-83-236786 and in set of 15 reports PC$115.00, PBV83-236995. The suggestion of compensation for research injuries has been a mainstay of ethical and public-policy discussions of research with human subjects for many years. The failure to resolve the issue exposes the entire research enterprise to the public recriminations that could follow from one or a series of serious, uncompensated injuries to subjects. The importance of biomedical and behavioral research for this country is manifested in the many billions of dollars that such research receives each year in an attempt to conquer disease and to relieve human suffering. The formal ethical standards and individual consciences of investigators, as well as Federal rules and guidelines developed in the past two decades, have done much to protect research subjects and to reduce the risk of injury to them. Some risk remains nevertheless -risk that through statistically small may manifest itself in serious ways for individuals. A social policy experiment is needed to see whether compensation programs might provide a feasible means to further reduce the risk of unremedied injury to, .... CAN'T READ KEYWORDS: *Workmens compensation, *Injuries, * Research projects. Available from the National Technical Information Service, Springfield, Va 22161 PRICE CODE: PC$8.00 FOR REFERENCE SEE (16bb01.gif) Compensating for Research Injuries A Report on the Ethical and Legal Implications of Programs to Redress Injuries Caused by Biomedical and Behavioral Research Volume One: Report June 1982 President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research Morris B. Abram. M.A. J.D.LL.D., Chairman New York, N.Y. George R. Dunlop, M.D. Daher B. Rabi, D.O. University of Massachusetts St. Clair Shores, Michigan Renee C. Fox, PhD., D.H.L. Anne A. Scitovsky,M.A. University of Pennsylvania Palo Alto Medical Research Foundation Mario Garcia-Palzaieri, M.D. University of Puerto Rico Seymour Siegel, D.H.L. Jewish Theological Frances K. Graham, Ph.D. Seminary of America University of Wisconsin New York Albert R. Jonsen Lynda Smith, B.S. S.T.M., PhD Colorado Springs, Colorado University of California San Francisco Charles J. Walker, M.D. Nashville, Tenessee Donald N. Medearia, Jr., M.D. Harvard University Carolyn A. Williams, PhD. University of North Carolina Arno G. Motulsky, M.D. Chapel Hill University of Washington *Sworn in February 11, 1982 Term expires February 11, 1982 Sworn in March 12, 1982 Staff Alexander M. Capron, LL.B., Executive Director Deputy Director Administrative Officer Barbara Mishkin, M.A., J.D. Anne Wilburn Assistant Directors Support Staff Joanne Lynn, M.D. Florence Chertok Alan J. Weisbard, J.D. Ruth Morris Clara Pittman Professional Staff Kevin Powers Mary Ann Baily, Ph.D. Nancy Watson Dan Brock, Ph.D. Andrew Burness, M.E.A. President's Commission Katharn Kelly, M.S. Commonwealth Fellows and Susan Morgan Student Interns Marian Osterweis, Ph.D. Joshua Abram (1980) President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research Renie Schapiro, M.P.H. Deborah Blacker (1980) Daniel Wikier, Ph.D. Cheryl Cooper (1980) Research Assistants Jeffrey Katz (1981) Michelle Lagmay Ruth Oretz (1981) Jeffrey Styker Henry S. Richardson (1982) Jennifer Setom (1980) Consultants David Tancredi (1980) Bradford H. Gray, Ph.D. William Thompson (1981) Dorothy (illegible) Mindy Werner (1982) 11 President's Commission for the Study of Ethnical Problems in Medicine and Biomedical and Behavioral Research (ILLEGIBLE) June 11, 1987 The President The White House Washington, D. C. 20500 Dear Mr. President: On behalf of the President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, I am pleased to transmit our Report on Compensating for Research Injuries. This study was undertaken at the request of the Department of Health and Human Services (HMS), although the concern that it addresses extends to agencies throughout the Federal government which conduct or support research with human subjects. In light of the Commission's earlier recommendation (conveyed in December 1981 in our first Biennial Report on Protecting Human Subjects) that HHS officially assume the role of lead agency in this field, we believe that HHS should be responsible for acting on the recommendations presented in the enclosed report. Other Federal entities can then benefit from the experience of HHS. Several Federal panels have previously recommended the establishment of a governmental program of compensation for injured research subjects. Although the Commission concludes that redress should be made for many such injuries, it recommends that no program be instituted at this time. Instead, it would seem advisable for HHS to conduct a small, contraction experiment to determine whether a formal program is needed and, if so, the most fair and efficient means of providing compensation. The Commission is pleased to have had an opportunity to assist in the resolution of this important topic. Respectfully, Morris B. Abram Chairman Copies to: Honorable George Bush Honorable Thomas P. O'Neill, Jr. 7 How Did This I Issue Arise? Preceeding Page blank 9 Introduction to the Social and Cultural Setting 1 The power of medicine to cure and to prevent illnesses has increased enormously during the present century. All those having access to medical care have been the beneficiaries. Advancements in preventive measures and therapeutic techniques have reduced the threat of early death and crippling disability. The result has been a significant improvement in the quality as well as the quantity of life. An outstanding feature of contemporary medicine is its committment to research and to the scientific application of research findings. Exploration and experimentation distinguish the new, more effective therapeutics from the old more than any other factor. Indeed, one of modern science's most visible and humanly significant contributions is the progress of medicine in the past half century. The social benefits of medical research have been enormous, and its value is reaffirmed with each successful act of treatment or prevention. The ratio of benefits to costs in medical experimentation has been remarkably favorable. This has been true not only of the dollar costs of laboratories and the like but also of the human costs sustained as research-related injuries. At the same time, however, these human costs must not be disregarded. New techniques, unless they are adopted blindly, must be tested, and testing in turn requires not only laboratory and animal studies, but also the use with human subjects of uncertain methods whose range of effects cannot be predicted precisely in advance. Risk is thus inherent in medical research, no matter how conscientious the investigator and careful the research. Quite obviously, not all experimental drugs and techniques prove to be more successful than other existing treatments; and many experiments are performed on healthy volunteers, who need no treatment in the first place. Even when a new treatment proves to be a relative success, the initial experiments may reveal that certain patients cannot benefit or may be especially susceptible to toxic side effects. Preceding page blank 10 Compensating for Research Injuries: Chapter 1 These untoward results of medical experimentation occur far less frequently than do the benefits, but to those who are affected they can be real and serious. Research-related injuries are harma 1/ that occur as a nearly unavoidable result of an enterprise undertaken for social benefit. Those who receive the benefits--and this includes nearly all members of society-- recognize a responsibility for collective support if the research enterprise is to be successful as is attested by the magnitude of funding for biomedical research from governmental bodies and charitable contributions. Naturally, that responsibility would seem to extend to the human costs of the research enterprise. The chapters which follow address the question: What is a fair system of fulfilling that responsibility? The issue is approached through consideration of the need for a program, the ethical arguments for and against, and the formulation of possible proposals and recommendation of a social policy experiment to test out alternative policies. The balance of this chapter attempts to sketch the social and cultural setting of the problem of research-related injuries. The cultural ethos colors one's appreciation of the facts specifically relevant to the issue. Furthermore, the problem of research injuries is not sui generis. It is but one instance of a much larger set of issues with which American society is presently grappling, that of the risks imposed by technological progress. For example, large-scale enterprises such as energy production and mass immunization, while conducted largely for the social good, put certain individuals at special risk. The plight of those, relatively few in number, who actually sustain injury is made vivid by the communications media and presents the nation with questions of conscience: Who is responsible for the welfare of these people? What are they owed, and by whom? Why are they put at risk, and should steps be taken to ensure that there will be no more victims? Our policy on research injuries will inevitably reflect the development of any public consensus on these 1. The terms injury and harm have distinct meaning in the law; the former connotes wrongfulness or the occurrence of something for which a plaintiff can seek redress. Ordinary discourse does not make so clear a distinction, however. In this Report, the terms are used synonymously to mean damage regardless of wrongfulness, fault, or responsibility. Since, in common parlance, the concern of the Report is with injured research subjects, injury will be the term used in most instances. Compensating for Research Injuries: Chapter 1 11 wider problems of risk. In turn, the policy on research injuries could conceivable influence the course of the larger debate and raises questions of "horizontal equity" in redressing injuries of one type but not of others. To explore the wider context in which the problem of compensation of injured research subjects arises, this chapter first considers the place of the research enterprise in society, that of the volunteer subject, and differing conceptions of the relationship between them. The varied, often inchoate, images of research and its subjects greately complicate the task at hand. In the next section, the Commission examines another factor that complicates thinking about compensation-- social attitudes toward risk and toward spreading the risks beyond those whom they touch directly. The chapter concludes by considering a number of basic social issues that underlie the debate over research injury. Roles and Relationships in Human Experimentation The Role of Elomedical and Behavioral Research. Since World War II, the magnitude of biomedical and behavioral research in the United States has increased tremendously, as has the Federal government's participa-tion. By 1980, health research had become an $8-billion-a-year enterprise, with over half the funding coming from the Federal government. 2/ through the National Institutes of Health and over twenty other agencies; furthermore, a large proportion of the privately sponsored research on drugs, medical devices, other consumer products and pesticides is conducted pursuant to extensive Federal regulation, although not supported by public funds. The centrality of research in medicine, particularly in American society in recent decades, makes it easy to forget that the role of the professional clinical investigator and the institutionalization of clinical research are historically recent 20th century developments. Nevertheless, over the past fifty years and particularly since World War II, certain changes are discernible in the settings and modes of organization of biomedical and behavioral research. A progressive shift has occurred from the type of small, collegial, personally directed units such as those depicted in the [2. National Institutes of Health. Basic Data Relating to the National Institutes of Health - 1380. U.S. Government Printing Office, Washington (1980). Figures 1 and 2, Tables 1-3.] 12 Compensating for Research Injuries: Chapter 1 1950's by Means and Fox. 3/ to massive sprawling institutions which often dominate the academic environments they inhabit or which are conducted under industrial and governmental control. Americans generally share the benefits of enhanced understanding of human physiology and advances in therapy. Similarly, although contributions to the public purse are not strictly proportionate, it is the citizenry as a whole that sponsors publicly supported research. Research, then is an enterprise that is collectively sponsored and responsive to the collective good. The widespread enthusiasm shown in recent decades for medical research can be at least partly explained by one single fact: all of us are threatened by disease and disability. The risks of nature affect everyone, rich or poor, black or white, male or female (though some risks are higher for less-advantaged groups). Research offers the promise of reducing some of these risks. Research can also help to reduce some of the risks imposed by health care itself, for a significant amount of clinical research is designed to test the safety and efficacy of currently accepted medical practices. For example, two clinical trials which spawned widely publicized litigation by injured subjects--the University of Chicago study of the use of diethyistilbestrol [DES] during pregnancy to prevent miscarriage, and the multi-center clinical trial with premature infants examining the relationship of oxygen therapy to the incidence of blindness resulting from retrolental fibroplasia-- provided the scientific basis of rejecting or modifying those therapies. Were such research never conducted, these therapies might still be employed in medical practice. 4/ Thus, acceptance of controlled risks in [3. J.H. Means Ward 4, Harvard University Press, Cambridge, Mass (1958): Renee C. Fox, Experiment Perilous, The Free Press, Glencoa, Ill. (1959).] [4. Some of the most important evidence about the effects of DES come from a controlled experiment at the University of Chicago in the early 1950's. Three of the women involved in this experiment are now suing the university for having put them at the risk. The university and others will be more careful in the future, thus increasing the risk that new cancer sources will go undetected. Meanwhile the fear of lawsuits is making doctors and hospitals reluctant to help track DES daughters, thus increasing the risks that some of them will get cancer who aren't caught in time. Compensating for Research Injuries: Chapter 1 13 clinical research can and regularly does, result in knowledge which reduces the "risks of everyday life," including those risks associated with standard medical care, for all members of the society. 5/ Increased freedom from risks is, then, one promise of research. But there is no easy path toward this goal. Scientists must test out hypotheses, and they must sometimes use human beings--meaning their own bodies or others--as a laboratory to understand normal physiology as well as abnormal considerations, and to fill in important gaps in knowledge about the efficacy and safety of new medical interventions. Thus, in its pursuit of preventive, diagnostic, and therapeutic interventions which are intended to reduce the risks caused both by nature and by human activities, research imposes other risks. These risks of research are borne by only a tiny fraction of the number of persons who face the risks of disease and disability that research is designed to combat. More importantly, the manifestation of these research risks as actual injuries is not spread evenly over the entire population; they occur for an unfortunate few among those who serve as subjects. The Role of the Research Subject. One's thinking on the question of compensation for research injuries is directly affected by the way in which one conceives of the subject's role. Two experts on these matters contend that "[p]art of the difficulties that have surrrounded legal and policy efforts to deal with the issue of compensating persons for research-related injuries--reside in our lack of understanding about the development, social roles and attributes of clinical research and its participants." 6/ Michael Kinsley, Fate and Lawsuits, 182 THE NEW REPUBLIC 20, 25 (June 14 1970) 5. In months, these facts, the Commission expresses no judgements on the ethical or legal questions, including those of informed consent, raised in ongoing or recently concluded litigation. 6. Judith P. Swazey and Leonard H. Glantz, A Social Perspective on Compensation for Injured Research Subjects (1981): see Appendix A to this Report. Major portions of this chapter are based upon this paper, which develops themes which emerged at a meeting of consultants with several members of the Commission's staff on November 25, 1981. In addition to Dr. Swazey of Medicine in the Public Interest and Professor Glantz of Boston University the participants included Commissioner Renee C. Fox and 14 Compensating for Research Injuries: Chapter 1 Research subjects may be popularly clothed with certain images--for example, those of hero, of victim, and of employee or contractor--and each of these images colors our conclusions about the character, moral status, and claims of the research subject. The appropriateness of providing compensation for research-related injury varies with the definition of the subject's role. For the hero, the wellsprings of public gratitude are overflowing: witness the donation of funds to provide $800,000 of accident insurance for the astronauts on the space shuttle. The claim of the victim is different, but also powerful; disclosure of the Tuskegee abuses resulted, finally, in the provision of compensation by the Federal government. 7/ And for an employee or contractor, compensation may be a matter regarded as a proper subject of negotiation. The category into which research subjects are placed also has a bearing on the importance and significance attached to the research subject's informed consent. The consent of a hero is not an issue; heroism results from spontan-eous action or deliberate "volunteering." The notion of victim, however, has quite different resonances; the victim is often passive and formal consent--if any has even been even obtained--may be viewed as uninformed or the result of duress. Consent is most compatible with the image of research subject as employee or contractor. Although questions may arise about the relative freedom and negotiating power of an employee compared with ___________________ professors Roy Lubove of the University of Pittsburgh, Barbara Rosenkrantz of Harvard University and Stephen Toulmin of the University of Chicago. 7. James H. Jones, BAD BLOOD, Freel Press, New York (1981) at 217-19. 15 FOR REFERENCE SEE (16bb02.gif) Compensating for Research Injuries: Chapter 1 16 or revelations about the research projects associated with the names Tuskegee, 9/ Willowbrook 10/ and the Brooklyn Jewish Chronic Disease Hospital 11/ focused renewed public attention on the possible abuses of the rights and welfare of subjects in the name of research. The importance of research, and the necessity and value of the research subject, continued to be affirmed. The horror stories were generally felt to be the unusual in-stances rather than the tip of an iceberg of "malre-search." Nonetheless, new protections for research subjects were put in place, designed to ensure that subjects participated voluntarily and that no unnecessary risks were imposed--in short, to prevent future research subjects from becomming victims. 12/ The growth of the clinical research enterprise dur-ing the 1960's and 1970's helped to shape another image of the research subject, one that seems to have increas-ing prominence today. As research increased in volume, especially with the growth of large controlled clinical trials, the role of the research subject became more rou-tinized and less visible. For many in the society, re-search subjects became less readily identifiable either as heroes or victims. A few research institutions now hire people as subjects quite in the manner of an ordin-ary job 13/ complete with negotiations over salary and benefits, and coverage under an insurance plan similar to workers' compensation. Moreover, a "consent form" is often viewed as a contract between a subject and an investigator. The question of how subjects ought to be viewed may have no satisfactory answer, simply because none of the images sketched here fit all subjects or fit any subjects uniquely. Indeed, the difficulty of choosing between these and other images probably accounts for some 9. Tuskegee Syphilis Study Ad Hoc Advisory Panel, FINAL REPORT, U.S. Department of Health, Education, and Welfare, Washington (1973). _________________ 10. Jay Katz, with assistance of A.M. Captron and E.S. Glass, EXPERIMENTATION WITH HUMAN BEINGS, Russell Sage Foundation, New York 1972) at 1007-1010. 11. ki at 9-65; Hyman v. Jewish Chronic Disease Hospital 15 N.Y. 2d 317.206 HN.E. 2nd 338 (1965). 12. John A. Robertson, The Law of Institutional Review Boards, 26 U.C.L.A. L. REV 434 (1978). 13. See e.g., pp. 53-56 Infra. 17 Compensating for Research Injuries: Chapter 1 of the difficulty encountered by this Commission and by other groups in deciding whether the prospective sub-ject's informed consent should be taken as relieving researchers and their sponsors of responsibility for the injured which may result. The arguments and programs set forth in this Report try to take into account the several images of research subjects and the probability that there may be some truth in each. The Relationship of Subjects to the Research Enterprise. The relationship of the various parties to the research enterprise may also be viewed in different ways. For example, the relationship of investigator to subject may be assimilated, perhaps unconsciously, into the physician-patient relationship. Indeed, many investigators are physicians, and many also are not. Physicians, in any case, are thought to have important obligations to their patients including, significantly, "primum non nocere." Seen in this light, a physician could have violated the patient-subject's therapeutic benefit; compensation could conceivably then be in order simply as a form of reparation. These obligations and rights do not obtain, however, if the investigator is instead conceived as one party who wishes to contract for the services of another (or the use of that person's body). But if the relationship is to be understood in the latter way, it becomes essential to take into account differences in power between subject and research institutions. Research subjects may be sick or poor and are not organized into unions or lobby groups. Subjects tend to be engaged in their "work" for relatively short periods of time. They are simply not situated to form a cohesive constituency to demand protection on a collective basis, the way other groups of workers have during the past century. Research facilities are usually large, imposing, and staffed by professionals of high social status. Indeed, research subjects at the National Institutes of Health or military hospitals face the power and authority of the government itself. Because of the inherent inequality of such relationships, the various parties to the research enterprise are not necessarily free and equal agents involved in a situation equivalent to ordinary negotiations for mutual benefit. The Relationship of Subjects to the Beneficiaries of Research. The relation of research subject to investigator and to research institution is not, however, the only one requiring attention. Also of importance is the relationship between subjects and the beneficiaries Compensating for Research Injuries: Chapter 1 18 of research. Once again, the significance of this relationship may be understood in several very different ways. It has been suggested, for example, that the use of human subjects in research be viewed as an instance of "gift exchange," characterized by three norms: to give, to receive and to repay. 14/ On this view, the subject gives by participating in research and, especially, by accepting the risk of injury; and a social disequilibrium results if injury occurs unless that gift is repaid in the form of compensation by the government acting as agent of the beneficiaries in society. A contrasting view, however, would regard compensation as a means of limiting the size of the gift bestowed by the research subject; but this might violate an obligation of society to FOR REFERENCE SEE (16bb03.gif) assess the amount the defendant must pay to make the plaintiff whole and also to declare the community's standard of conduct as a warning to individuals in the future. But many injuries arise today which do not seem to have been caused directly by a single individual: numerous separate actions, some by institutions rather than individuals, often widely separated in time and space from the injury, must coincide for an injury to occur. The instrumentalities of harm are like the boy in the rhyme who "shot an arrow in the air, it fell to earth [he] knew not where." The chain of causation and responsibility may becvome so tangled as to preclude anything other than an arbitrary assignment of liability on the parties seen as best able to bear the costs. Although the growth of nonfault liability in several areas (most notably, for injuries caused by consumer products) has removed the additional burden of trying the issue of negligence, the complex problems of causation still remain. The collapse of the second part of the ancient paradigm of risk--the uncomplaining acceptance of a divinely ordained fate--is well illustrated in the recent litigation over risks of cancer allegedly imposed by use of DES. It is well nigh impossible for an individual plaintiff in a DES case to prove that her vaginal cancer resulted biologically from her mother's having been given DES while the plaintiff was in utero. Instead, causation is established as a statistical matter by showing that it is more probable than not that the injury came from the administration of DES. To women with other forms of cancer, the compensa-tion of the DES daughters, other than seeming a _________________ 14. M. Mauss, THE GIFT: FORMS AND FUNCTIONS OF EXCHANGES IN ARCHAIC SOCIETIES, I. Cunnison (trans). The Free Press, Glencoa, Ill. (1954) 19 Compensating for Research Injuries: Chapter 1 great triumph may appear instead a failure of science and society to establish the cause of their own grievous harm and to provide compensation. It does not matter that for many (perhaps even for most), there is no single "cause" in the legal sense of the word as employed in the DES litigation, but rather a coincidence of factors from genes to workplace environment, from health care to personal habits. What matters is that redress is avail-able to some, while others are told that it is just fate. Yet, as a commentator recently pointed out, it is nonsen-sical to rule that cancer is a matter of fate only inso-far as its cause is unknown. 16/ Any attempt to spread some risks has the danger of seeming unfair for failing to spread all risks. Risks in the biomedical sphere have posed special problems of late for the existing means of cost-allocation. Although partiality is, thus, always a danger, there may be reasons for special attention to providing compensation for research injuries. While one must take care not to oversentimentalize the investigator-subject relationship, one need not reject legitimate opportunities to support its positive, moral attributes. From this perspective, a compensation program based on human need rather than fault and enlisting investigators as proponents of the claims of injured subjects rather than as adversaries in a courtroom battle, takes on an additional social mean-ing, a meaning specially suited to the nature of the investigator-subject relationship and their joint venture into the unknown. In this respect, a program for non-fault compensation diverges sharply from the existing medical malpractice framework, with its insidious effects on the doctor-patient relationship. The Commission notes that policymakers in the United States are not alone in considering this problem. In Sweden, insurance coverage has been available since 1975 to provide compensation to subjects injured as a result of participation in biomedical research. 17/ Similarly, accident insurance has been available at the University of Leiden (The Netherlands) since 1976 for medical re-search projects determined by the Committee on Medical _________________ 16. Michael Kinsley, Fate and Lawsuits, 182 THE NEW REPUBLIC 20[June 14, 1980]. 17. Harry Bostrom. On the Compenation for Injured Research Subjects in Sweden (1980): see Appendix K to this Report. Compensating for Research Injuries: Chapter 1 20 Ethics to warrant such coverage. 18/ In March 1978 a Royal Commission (the "Pearson Commission") reported to the British Parliament its recommendation that "any volunteer for medical research or clinical trials who suffers severe damage as a result should have a cause of action, on the basis of strict liability, against the authority to whom he has consented to make himself available." 19/ Finally, in 1980, a World Health Organization working group to develop international guidelines for human experimentation concluded that "natural justice demands that every subject participating in medical research should have automatic entitlement to reasonable and expeditious compensation for any injury sustained as a result of participation." 20/ Proposed guidelines reflecting that conclusion are under consideration by the World Health Organization and the Council for International Organizations of Medical Sciences. Research Injuries and the Larger Social Context Concerns about compensation to injured research subjects reflect an ambivalence in individual and social views regarding research and risk. On the one hand, there is a general understanding and acceptance in this society that research is a social good which provides us with beneficial knowledge and techniques. On the other hand, investigations by Executive and Congressional bodies and the advent of public regulations for protection of human subjects manifest the increasingly widespread concern about the motives of researchers, the consequences of research, and the use of human beings as experimental objects. Compensation of injured research subjects is but one of several interrelated social responses to these tensions. In recent decades, much emphasis has been placed on the informed consent of research subjects and on the regulation and limitation, of risks incurred in research. Compensation provides a third element, complementing these first two when injuries occur in even well-designed, carefully conducted research on informed and consenting subjects. [These themes ________________ 18. E. L. Noach, Materials Concerning Compensation of Subjects Injured in Research at the University of Leiden, The Netherlands (1980): see Appendix L to this Report. 19. Royal Commission on Civil Liability and Compensation for Personal Inbjury. REPORT. Her Majesty's Stationery Office, London (1978). Vol 1 at 286. 21 Compensating for Research Injuries: Chapter 1 are explored more fully in the next chapter.] But just as compensation is only one facet of the social, ethical, and legal concerns about the conduct of research with human subjects, so the concern with the protection of human subjects, in turn, has been generated and responded to in relationship to broader societal concerns. Human experimentation has both reflected these broader concerns and helped to foster them. This linkage is particularly evident with respect to three closely related aspects of contemporary American society. First, one finds today an enhanced concern with victims--real, imagined, or potential--of all kinds. 21/ Second, there is a new awareness of the inequality of some groups' bargaining power. 22/ Third, populist doubt and suspicion about "big" and "powerful" institutions such as government, medicine, and science has been renewed and extended to the authority and power vested in "experts" of all kinds. 23/ These social trends, coupled with a new assertive-ness by members of groups who have suffered from unequal and unfair treatment in the past and who now insist that their rights be recognized, have forced Americans to reexamine, and to act upon, their standards of personal, institutional, and governmental responsibilities. The social movements of recent years have clearly had an im- pact on thinking about the rights of research subjects; they cause one to rethink the treatment of and responsi- ______________ 20. John F. Dunne. Proposed International Ethical Guidelines for Human Experimentation, XIVth CIMOS Round research. Compensation provides a third element, Table Conference Session 1 [Medical Ethics and Medical Education]. Mexico City (1980). 21. See, e.g., Marshall S. Shapo. A NATION OF GUINEA PIGS: THE UNKNOWN RISKS OF CHEMICAL TECHNOLOGY. Free Press, New York (1979): Proposed Amendments to Title 28 of the U.S. Code: Hearings on Radiation Compensation (S. 1483) Before the Senate Committee on Labor and Human Resources, 97th Cong., 1st Sess. (Oct. 27, 1981): Joe Hudson and Burt Galaway (eds). CONSIDERING THE VICTIM, Charles C. Thomas Springfield, Mass. (1975). 22. See Swazey & Glantz supro note 6 at 10: 15 U.S.S. 57 a(b). 1975 Magnuson-Moss FTC Improvement Act (expense reimbursement to permit public participation in rulemaking). 23. Loren R. Graham. Conerns about Science and Attempts to Regulate Inquiry 107 DAEDALUS 1 (1973). Compensating for Research Injuries: Chapter 1 22 bilities toward members of this class of persons. Correlatively, abuses suffered by a few research subjects have themselves contributed to this wider social questioning. The confluence of concerns with victims, unequal bargaining power, and powerful institutions is strikingly illustrated by apprehensions about the ways researchers and research agencies, including the Federal government, can mislead, exploit, or injure subjects in the name of patient welfare, scientific progress, or public good. To the earlier reports of projects at Willowbrook and Tuskegee have recently been added revelations of the experiments with psychotropic drugs sponsored by the CIA and the Defense Department's biological warfare testing accidents at the Dugway Proving Ground. 24/ All have been lightning rods for attracting attention to problems in governing research and in testing human subjects with fairness and due concern. The research injuries with which this Report is concerned are not primarily those that result from unethical practices on the part of investigators. Most of the examples receiving current attention are actually old experiments, recently come to light or the subject of contemporary reexamination. 25/ The focus of this Report is on harms resulting from risks of relatively low frequency and severity, visited on subjects of well-planned, carefully conducted ethical research. It must be recognized, however, that social attitudes toward the compensation of those harmed in ethical research will be colored through abuse. Risk and injury are common to 24. Biomedical and Behavioral Research: Human-use Experimentation Programs of the Department of Defense and Central Intelligence Agency: Hearings on S. 2515 Before the Subcommittee on Health of the Senate Committee on Labor and Public Welfare and the Subcommittee on Administrative Practice and Procedure of the Senate Judiciary Committee, 94th Congress, 1st Session (1975). 25. See e.g., Jones supro note 7: Roberrt Gorner, John W. Powell and Bert V. A. Rolting, Japan's biological Weapons: 1930-1945, 37 BULL. OF THE ATOMIC SCIENTISTS 43 (1981). This article is based in part on documents released under the Freedom of Information Act which reveals that in World War II, the Japanese had used prisoners of war as subjects of research at biological warfare experimental stations. The records of these experiments had been turned over to representatives of the United States in exchange for immunity from war crimes prosecution. 23 Compensating for Research Injuries: Chapter 1 both kinds of research, and these will likely be the chief subject of moral concern. The centrality of risk in the conduct of research is testified to by the devel-opment of a new lexicon--necessary risk, acceptable risk, risk acceptance, danger-of-danger, risk-of-risk, uncer-tainty-of-uncertainty--and in the emergence of a new occupational category of institutional "risk managers". The Commission's study of compensation for research injuries represents an attempt to explore how much ine-quality and risk are required by the research enterprise, and to examine the justice of the existing distribution of risks (to subjects) and benefits (to the wider soci-ety). In the course of this inquiry, three sets of issues have been identified: they set the framework for this Report. The Basis for Public Policy. Existing data reviewed in Chapter Four suggest that the number of research injuries, and particularly of uncared-for injuries is not large. Further, the creation of a compensation system would entail both economic costs and administrative bur-dens. Thus, the creation of a compensation program is potentially susceptible to attack on narrow cost-benefit grounds, particularly when viewed against other social programs and priorities. The ultimate persuasiveness of this attack cannot, however, be determined on the basis of existing data. On the other hand, commentators often criticize the inability of our governmental system to respond to prob-lems in advance of a crisis or a catastrophe. Scientific research entails risks, and the laws of probability decree that such risks will, someday, result in harms. Here the government has the opportunity to anticipate, rather than react to, headlines-in-the making--headlines which may breed lasting public mistrust of science. Further, how the government responds to the problem of victims of research injuries will both reflect and help to determine the kind of society we wish to be, and to become. Thus, the question looms: Is policy to be determined solely by cost-benefit calculations, or is there room in the policymaking process for an additional dimension of social values and responsibility? Social Responsibility and Individual Consent. As manifested in judicial opinions, ethical codes and Feder-al regulations, this country has determined both that informed consent is a prerequisite to participation in biomedical and behavioral research and that research posing unjustifiable or otherwise unacceptable risks may not go forward. But what of risks which cannot, or ought Compensating for Research Injuries: Chapter 1 24 not, be avoided? If competent individuals knowingly consent to run the risk of participation in research without the expectation of compensation in the event of injury, ought not that altruistic gift be respected? Or is such a gift more than society should request or even accept? Does there come a time when to rely on "informed consent" is to exploit the goodness--or the weakness--of those who deserve society's respect and gratitude instead? Administrative Practicability and the Plight of the Helpless. A compensation program which excludes therapeutic research (or more generally, sick patients) is markedly simpler and less costly to administer than a more comprehensive program. Yet it is precisely in cases of therapeutic research involving sick patients that the subjects may be most in need and that the quality of consent given is most likely to diverge from the ideal. Three options present themselves: . to exclude such classes of research or research subjects from coverage entirely; . to experiment with novel methods of determining causation, extent of injury, and other factors in a fashion designed to reconcile need, "deservingness," and administrative feasibility; or . to abandon the requirement linking the injury to the research and instead provide medical care and financial assistance solely on the basis of human need. Is our society prepared to accept the notion of social responsibility embodied in this last option--a notion consistent with broadened social responsibility not merely for research injuries, but for all the vicis-situdes of modern life? If not, where should the line be drawn? Fortunately, the Commission was not charged with resolving these large questions in the abstract, and it has not sought to do so. Rather, the Commission has grappled with these themes as they apply to the concrete and immediate issue of compensation for research injuries. In recognizing that some questions are, finally, unanswerable, the Commission also recognizes that in a dynamic society, the quest for perfect and eternal answers may invite paralysis. Historical Perspective 2 In the history of biomedical ethics, discussion of compensation for research-related injuries has taken place against a background of shifting emphasis on two other mechanisms for the protection of human subjects: informed consent and limitation of risks. In the period immediately following the Nuremburg trials, concern focused primarily on the need for voluntary, informed consent through which potential subjects could either agree or decline to accept the risks inherent in a particular research activity. It was thought that a research institution could discharge its obligations to research subjects primarily by assuring that they were fully and fairly informed of the risks involved. Later it became apparent that informed consent was not always sufficient protection: subjects had been recruited for projects that seemed (at least to outsiders) to have entailed unreasonable risks. Therefore, procedures were adopted by the Federal government requiring prior review of research protocols to control or limit the amount of risk to which subjects might be exposed. This chapter describes the development of arguments for compensation against a backdrop of the formal implementation of other protective mechanisms for informed consent and risk limitation. The complexity of the relationships among these three themes (informed consent, limitation of risk, and compensation) and the shifts of emphasis over time best lend themselves to analysis through a division of the recent past into two periods: 1945-1966 and 1966 to the present. Reliance on Codes and Consent (1945-1966) Outside Encouragement for Self Regulation. In the wake of the Nuremberg trials of Nazi war criminals after World War II, concern about voluntary informed consent was the central focus of biomedical research ethics. Because of the horror that greeted revelations about the abusive and unethical experiments that had been performed on unconsenting prisoners by the Nazi physicians on trial, the first principle of the Nuremberg Code states that "the voluntary consent of the human subject is Preceding page blank 25 Compensating for Research Injuries: Chapter 2 absolutely essential. 1/ Subsequent codes adopted by individual countries and medical associations were derivative of the Nuremberg judgement. They too placed primary emphasis on assuring that the consent of research subjects is truly voluntary and based upon a full understanding of the risks in-volved. 2/ Disclosure of the risk was deemed of primary importance; limitation (if any) on the amount of risk that might be voluntarily assumed by subjects was secon-dary and generally took the form of exhortations to researchers to satisfy themselves that the risks of the research are justified by the anticipated benefits (to the subject or to general knowledge) and not to inflict death or disabling injury. These limitations derive from principles five and six of the Nuremberg judgement pro-hibiting experiments "where there is a-prioi reason to believe that death or disabling injury will occur" and caution that risk should never exceed "the humanitarian importance of the problem to be solved by the experiment." Hence, in the mid-1950's when the first suggestions for provision of compensation for injured research subjects appeared in print, there were no regulations or review procedures to limit the risk that might be presented in research. In fact, Irving Ladimer reported in 1955 that there had been two recent deaths associated with biomedical research: a laboratory technician, following an overdose of an experimental drug, and a prisoner, following an injection of hepatitis virus. 3/ Commenting on the general problem of research-related injuries, Ladimer noted that "commercial insurance ___________ 1. United States v. Brandt 2 TRIALS OF WAR CRIMINALS BEFORE THE NUREMBERG MILITARY TRIBUNALS (The Medical Case) 181 (Military Tribunal I. 1947). 2. See, e.g., Principles for Those in Research and Experimentation adopted by the General Assembly of the World Medical Association in 1954: Report on Human Experimentation, Public Health Council of the Netherlands (1955); Ethical and Religious Directives for Catholic Hospitals, adopted by the Catholic Hospital Association of the Unites States and Canada (1955); Responsibility in Investigations on Human Subjects, Medical Research Council, Great Britain (1963). All are reprinted in Henry K. Beacher, RESEARCH AND THE INDIVIDUAL, Little Brown and Co., Boston (1970). Appendix A. 3. Irving Ladimer, Law and Medicine: A Symposium 3 . PUB L. 467, 473 (1955). Compensating for Research Injuries: Chapter 2 26 coverage and provision of medical care for consequences directly related to the [research] project are methods observed by responsible organizations." 4/ No references or examples were cited, however. In an unpublished doctoral thesis, Ladimer subsequently examined the liability to which research investigators were exposed and concluded that "a doctrine of liability without fault may be imposed, on the theory of a social cost of medical research, resembling the concepts supporting programs such as workmen's compensation." 5/ He further observed that in fashioning a remedy for injured subjects, "public attitude as well as precedent law will be decisive." 6/ The idea of providing compensation for injured research subjects was proposed more formally in a 1960 article in the Duke Law Journal, in which Donald P. Dietrich discussed the possible application of a nonfault compensation scheme to subjects of psychological research. 7/ Although he acknowledged that measuring the harm and establishing the amount of damages would be more difficult in the case of psychological injuries, Dietrich claimed [citing a half dozen articles on tort liability for psychic injuries] that the difficulties of proof would not be insurmountable. 8/ ______________ 4. Id at 509. 5. Irving Ladimer, LEGAL AND ETHICAL IMPLICATIONS OF MEDICAL RESEARCH ON HUMAN BEINGS, unpublished dissertation: submitted to the George Washington University School of Law, at 153 (1958) (on file in the Law School Library). 6. Id at 154 7. Donald P. Dietrich, Legal Implications of Psycho-logical Research with Human Subjects, 1960 DUKE L. } 265-274. 8. Id. at 273, citing: Smith, Relation of Emotions to Injury and Disease: Legal Liability for Psychic Stimuli, 30 VA I., REV 193-252 (1944): McNieca, Psychic Injury and Tort Liability in New York, 24 ST. JOHN'S I. REV 1 (1949): Smith, Medical Evidence in Industrial Injury Cases with Special Reference to Neuropsychiatric Claims, in Workmen's Compensation Problems, 187 (1954); Worden, Some Neglected Aspects of Injury, Mental Anguish and the Concept of Psychic Damage, 3} PUB. L. 377 (1954): Report of the New York State Law Revision Commission. STUDY RELATING TO INJURIES RESULTING FROM FRIGHT OR SHOCK, Leg. 27 Compensating for Research Injuries: Chapter 2 A problem that would come to have more significance in philosophic debates on the subject a decade later also emerged in Dietrich's article: the effect that a subject's knowing acceptance of the risk should have on the experimenter's responsibility to compensate for any injuries. Dietrich pointed out that although a subject may have known and consented to what the experimenter intended to do, still, he may not have fully realized the risks involved. "Mere knowledge of the facts which create the risk of harm is not enough unless there is a true appreciation of the nature and extent of the risk...." 9/ Dietrich's skepticism regarding potential subject's ability to appreciate risks foreshadowed adoption of other protective devices based, in part, on studies that provided empirical verification of his concern. 10/ After analyzing the possible theories and probable outcome of a suit for damages that might be brought by someone injured as a result of participating in psychological research, Dietrich then described the broad outlines of a nonfault compensation scheme. Because his discussion so closely resembles subsequent discussions appearing over the next twenty years, it is worth repeating in its entirety. 11/ Within an analytical framework such as this, then the first human experimentation case may be decided, and a hitherto unaccounted--for element of the true cost of such experimentation distributed. Such an extension of the law, however, will not resolve the dilemma of society's needing research while at the same time requiring due legal protection for both experimenter and subject. The resolution of this dilemma can be premised Doc. No 65 {E} (1935). _______________ 9. Dietrich, supra note 7, at 272. 10. See, e.g., Chauncey Starr and Chris Whipple, Risks of Risk Decisions, 208 SCIENCE :114 (1980); Vincent T. Covello and Joshua Menkes. Issues in Risk Analysis, paper presented at AAAS meeting, San Francisco (January 1980), to be published in AAAS Symposium Volume: RISK IN THE TECHNOLOGICAL SOCIETY. 11. Dietrich, supra note 7, at 273-274, original citations omitted. Compensating for Research Injuries: Chapter 2 28 upon the recognition that society is more than the ultimate beneficiary of research: through governmental action, society is the initiator of most research. This condition alone, it would seem, should justify the following: [1] A policy of liability without fault should be evolved for harm resulting from psychological experimentation. [2] Where the government undertakes or participates in the research program, it should also assume the burden of making injured subjects whole, through treatment and rehabilitation and by the payment of monetary compensation. [3] The government should consider such an underwriting program as would be required to assume costs to subjects taking part in private research programs conducted under modern, controlled conditions. Among the effects of such developments on the whole environment of psychological experimentation would be compensation of the injured subject without regard to the doubtful questions of liability and proof of injury, thereby encouraging the participation of a sufficient number of subjects of varying levels of personality integration. Further, there would also be legal protection for the experimenter who is part of an approved modern, controlled research program, thus encouraging research conducted on high planes. On the other hand, experimenters not of this class--those who are not associated with approved modern, controlled research programs-- would be strictly liable for any harm which results from their inducing others to serve as subjects of their research." Admittedly, the effect may be to discourage to some extent research which is not specifically socially sanctioned. Finally, national research effort in this area would become more ordered in the sense and to the extent that the essentiality of each research program, as balanced against the program's total cost, would be the basis for 29 Compensating for Research Injuries: Chapter 2 go-ahead decisions by agencies having in view the entire research picture. It is not surprising that Dietrich, writing at a time when there were few other formal controls in research, saw a compensation program not merely as a means of redressing injuries, but also of social control and resource allocation. Meanwhile, requirements for informed consent were added to Federal law as part of the 1952 Kefauver-Harris amendments to the Federal Food, Drug, and Cosmetic Act. 12/ The legislation--passed following the birth of a number of severely deformed children to women who had taken the sedative thalidomide during pregnancy--was intended to increase Federal control of drug testing in general and to require that prescription drugs be proven effective, as well as safe, prior to marketing. 13/ As part of the conditions imposed for testing new drugs, Congress required that sponsors of such investigations assure that they would (a) inform any human beings involved in the tests that the drugs were being used for investigational purposes, and (b) obtain the consent of the subjects or their representatives (unless it is infeasible to do so or, according to professional judgement, contrary to the best interest of a particular patient/subject}. 14/ One apparent result of the Kefauver-Harris amendments was an increase in the amount of research with human subjects conducted in this country and abroad to provide the data needed to support new drug applications. Emphasis on informed consent culminated in the Declaration of Helsinki, adopted by the World Medical Association in 1964. The Declaration distinguished {as had the Medical Research Council of Great Britain, a year earlier} between "clinical research combined with patient care" and nontherapeutic clinical research." For the former, the Declaration urged that informed consent be obtained "if at all possible, consistent with patient psychology." For nontherapeutic research, consent of the subject was urged in all cases with the exception that if the subject was legally incompetent, consent of a legal guardian should be procured. The Declaration also established the basic principle that the inherent risks ________________ 12. 76 Stat. 780, 87th Cong., 2d Sess; Oct 10, 1982. See 21 U.S.C. 355. 13. 21 U.S.C. 335[i] 14. Id Compensating for Research Injuries: Chapter 2 30 of research should be "in proportion to" the anticipazted benefits to the subject or to others. Apparent Problems in a Mighty Enterprise. Between 1945 and 1985 the annual research expenditures of the National Institutes of Health had increased many hundredfold from $701,800 to $456,600,000. 15/ This was a reflection of vast public support of biomedical and behavioral research in the aftermath of World War II based upon an appreciation of the benefits to be derived from scientific progress. Throughout this period, great attention was also paid to the ethical issues surrounding the conduct of research with human subjects. In 1960, the Law-Medicine Institute of Boston University received a large grant from the Public Health Service to investigate the legal and ethical aspects of research with human subjects. 16/ In 1963, the Institute published a major anthology on Clinical Investigation in Medicine: Legal, Ethical and Moral Aspects. Although major emphasis continued to be on problems of informed consent, suggestions for "group consideration" or prior review of research began to appear as well. 17/ Experience during the period 1955-65 moved the discussion from an academic to a public arena as it became apparent that some research subjects were truly being exposed to risk for the benefit of others. In some cases, the subjects assumed the risks unknowingly; in other cases, although the subjects may have consented, it was questionable whether they should have been asked--or permitted--to do so. Although such cases were few, compared to the amount of clearly acceptable research being conducted, the publicity attending questionable cases heightened public awareness and concern. One of the first incidents to alarm the general public took place at the Jewish Chronic Disease Hospital in Brooklyn, N.Y. The widely publicized case involved two physician-investigators who injected cultured cancer ____________ 15. Data supplied by Dr. John Sherrman, of NIH, reported by Henry K. Beecher in Ethics and Clinical Research, 274 NEW ENG. J. MED. 1354, 1355 (1966). 16. Irving Ladimer and Roger W. Newman (eds.), CLINICAL INVESTIGATIONS IN MEDICINE: LEGAL ETHICAL AND MORAL ASPECTS, Law-Medicine Research Institute, Boston University (1983) at iv. 17. Id at 108-210. 31 Compensating for Research Injuries: Chapter 2 cells into debilitated, elderly patients under their care, without informing the patients or gaining their consent. The research was funded, in part, by the Public Health Service. 18/ In 1965, after a series of hearings and recommendations of the appropriate grievance committees, the New York Board on Medical Licensure and Discipline accepted a determination of the Medical Grievance Committee that the two principal investigators had been "guilty of fraud or deceit in the practice of medicine and of unprofessional conduct." 19/ Both physicians were placed on one year's probation, but the recommended suspension of their licenses to practice medicine was stayed. 20/ In 1966, Dr. Henry K. Beecher of the Harvard Medical School published a landmark article in the New England Journal of Medicine describing a number of research projects he viewed as unethical largely because of the risks to which the subjects had been exposed. 22/ Some of the experiments he described involved withholding treatment from control groups without their knowledge or consent. Others, however, involved the use of medical or surgical procedures of considerable risk (cardiac catheterization, liver biopsy) for research purposes. In one case, reported Beecher, an investigator had transplanted a melanoma (cancerous tumor) from a dying patient to her mother; although the tumor was excised shortly thereafter, the mother died a little over a year later from diffuse melanoma that had spread from the small piece of transplanted tumor. 22/ Beecher's article drew national attention both be-cause it appeared in the prestigous New England Journal and because it was written by a highly respected physic-ian. Moreover, the examples were drawn from reports published in a leading (unnamed) biomedical journal. 23/ ________________ 18. Jay Katz, with the assistance of A. M. Capro: and K. S. Glass, EXPERIMENTATION WITH HUMAN BEINGS, Russell Sage Foundation, New York (1972) at 19. 19. Id at 63 20. Id. 21. Henry K. Beecher, Ethics and Clinical Research, 274 NEW ENG. J. MED. 1354 (1956). 22. Id at 1356. 23. Id at 1335. Compensating for Research Injuries: Chapter 2 32 Noting that Englishman M. H. Pappworth was then in the process of assembling over 500 papers based upon unethical experiments, Beecher concluded that "unethical or questionably ethical procedures are not uncommon." 24/ In his introduction to the article, he had said 25/ I believe the type of activities to be mentioned will do great harm to medicine unless soon corrected. It will certainly be charged that any mention of these matters does a disservice to medicine, but not one so great, I believe, as a continuation of the practices to be cited. An ethical approach to research with human beings required, in Beecher's view, that "the gain anticipated from an experiment must be commensurate with the risk involved. An experiment is ethical or not at its inception." 26/ He concluded that assuring this ethical approach rests primarily upon two factors: informed consent of the subject, and "the presence of complication, even if considered FOR REFERENCE SEE (16bb04.gif) minor," and confirmation that the coroner was notified in the case of any death resulting directly or indirectly from the experiment. 31/ (NOTE THAT REFERENCES IN THE MANUSCRIPT JUMP FROM 26 TO 31) Prior Review and Limitations on Risk (1966-Present) In 1966, the Surgeon General of the United States directed that all research proposals submitted for financial support from the Public Health Service must undergo prior review by an investigator's institutional associates "to assure an independent determination of the protection of the rights and welfare of the individual or individuals involved, of the appropriateness of the methods used to secure informed consent, and of the risks and potential medical benefits of the investigation." 32/ ________________ 24. Id. 25. Id. at 1354 26. Id. at 1330 27. Id. at 209-210 31. Id. at 209-210 32. Surgeon General, Memo to Heads of Institutions Conducting Research with Public Health Service Grants [February 8, 1966]. 33 Compensating for Research Injuries: Chapter 2 Prior review of research by a medical committee composed of medical staff had been an established procedure in the United States at the Clinical Center of the National Institutes of Health since its opening in 1953. 33/ In April, 1971, another controversial research project received major public attention when the British medical journal, Lancet, published a sharp criticism of experiments which involved injecting hepatitis virus into mentally retarded children at the Willowbrook State School in New York. 34/ The investigators justified their research by reference to the circumstances of their subjects: (1) they were bound to be exposed to the same strains under the natural conditions existing in the institutions; (2) they would be admitted to a special, well- equipped and well-staffed unit where they would be isolated from exposure to other infectious diseases which were prevalent in the institution.... (3) they were likely to have a subclinical infection followed by immunity to the particular hepatitus virus; and (4) only children with parents who gave informed consent would be included. 35/ The Willowbrook studies had been extensively criticized by theologian Paul Ramsey, in 1970, for exposing institutionalized children to unknown and unjustified risks. 36/ Others now quickly joined in the debate. 37/ _____________ 33. Stuart M. Sessoms, Guiding Principles in Medical Research Involving Humans, National Institutes of Health, 32 HOSPITALS 44 [1958]. 34. Stephen Goldby, Experiments at the Willowbrook State School, 1 LANCET 740 (1971). 35. Saul Krugman, Experiments at the Willowbrook STate School, 1 LANCET 740 (1971). 36. Paul Ramsey, THE PATIENT AS PERSON, Yale University Press, New Haven, Conn. (1970) at 47-55. 37. PROCEEDINGS OF THE SYMPOSIUM ON ETHICAL ISSUES IN HUMAN EXPERIMENTATION: THE CASE OF WILLOWBROOK STATE HOSPITAL (May 4, 1972), published by the Urban Health Affairs Program, New York University Medical Center. Compensating for Research Injuries: Chapter 2 34 At the same time that attention was being focused on the need to limit the risks to which subjects might be exposed, some authors continued to press for a nonfault compensation program for injured research subjects, either as a mechanism for controlling risks or as a matter of societal obligation. 38/ In a 1967 article in the Journal of the American Medical Association, Richard Bergen proposed that injuries arising from participation in clinical research be included in malpractice insurance coverage already held by sponsoring institutions. 39/ He viewed such coverage as the "ideal solution" to the problem because the sponsoring organizations would be able to provide insurance for physicians working under their auspices at less cost than if the physicians were to purchase the insurance invidually; moreover, paying for such coverage is an "appropriate cost for the sponsoring institution to pay." 40/ Several months later, Delford L. Stickel, M.D., approached the matter from the perspective of a physician interested in organ transplantation but also concerned about normal volunteers in biomedical research. Writing 38. The call for compensation had begun again shortly before the dramatic events of 1966: [S]ince the benefits of research redound to society, society should accept the responsibility for assuring that theinvestigator who proceeds with care and caution should not be inhibited in his research because of any inherent hazard. Likewise, the partner- subject--the "clinical material" for the investigator--should not be placed at disadvantage, if injury should result directly from his participation. The cost of protection should therefore be considered a proper charge to the business of doing research, to be assumed by the sponsor, in much the same way as other administrative costs are borne by government or industry in production and service operation. Irving Ladimer. Clinical Research Insurance [editorial], 16," CHRON. DIS., 1229, 1233 (1963). __________________ 39. Richard Bergen, Insurance Coverage for Clinical Investigation, 201 J.A.M.A. 305-306 (1967). 40. Id 35 Compensating for Research Injuries: Chapter 2 in Law and Contemporary Problems, Stickel adopted and forcefully supported Bergen's suggestions, recommending that the insurance be of a nonfault variety and adding two observations: (1) that the premiums set for the insurance coverage "would provide useful checks on overly dangerous reseaarch" and (2) that regulations or legislation establishing a duty to provide such insurance might be necessary. 41/ The arguments in favor of a compensation mechanism as a means to control research were elaborated but ultimately doubted by Yale Law Professor Guido Calabresi. 42/ Writing in a special issue of Doedalur in 1969, devoted to "Ethical Aspects of Experimentation with Human Subjects," Calibresi examined issues of risk-taking and methods for protecting human lives through indirect controls such as those operating in accident law. His support for a system of compensation rested on the perceived need to impose better controls on the research enterprise. Calabresi argued that having to compensate for research injuries would stimulate better analysis of the possible risks and benefits of a given research proposal. He saw the indemnification of injured subjects as a secondary, although desirable result. 43/ In the end, however, Calabresi concluded that he did not believe a compensation fund would be the best method of controlling the research enterprise: instead, he recommended review committees at the research institution [with diversity of membership as subsequently required by HEW]. His discussion of a compensation fund, he emphasized was "primarily to indicate that very little work has gone into the search for complex control devices that would balance present against future lives and still put no one in the position of clearly deciding against individual lives. 44/ Complex control devices in the form of local review committees were even then, being developed by HEW (now ___________ 41. Delford L. Stickel, Organ Transplantation in Medical and Legal Perspectives, 32 LAW AND CONTEMPORARY PROBLEMS 5907, 809 n. 32 (1967). 42. Guido Calabresi, Reflections on Medical Experimentation in Humans, in EXPERIMENTATION WITH HUMAN SUBJECTS {ed. by Paul Freund}. George Braziller, New York (1970). 43. Id at 395. 44. Id. at 396-399. Compensating for Research Injuries: Chapter 2 36 HHS), and were soon to be implemented. The development of DHEW policy for protection of human subjects and its conversion to Federal regulation is part of the final phase of this story. Strenthening Regulations. The decade of the 1970s was one of extraordinary Federal activity in the review and regulation of research ethics, both in Congress and in the administrative agencies. In response to rising concern about the need to protect human subjects, the Public Health Service in 1971 extended the 1966 Surgeon General's memorandum into a formal Institutional Guide to DHEW Policy on Protection of Human Subjects to explain HEW's grant administration policy. It contained an important modification of the Surgeon General's requirement that research supported by HEW grants and contract undergo "peer review" at the investigator's institution.45/ The committee must be composed of sufficient members with varying backgrounds to assure complete and adequate review of projects....No member of an institutional committee shall be involved in either the initial or continuing review of an activity in which he has a professional responsibility....The committee should be able to determine acceptability of the proposal in terms of institutional commitments and regulations, applicable law, standards of professional conduct and practice, and community attitudes. Similar review requirements had already been incorporated in FDA regulations governing investigational new drug studies. 46/ The HEW policy explicitly required that the risks of any research project be justified either by the potential benefits to the subjects or by the importance of the knowledge to be gained, and cautioned review committees to "be alert to the possibility that investigators, program directors, or contractors may, quite unintentionally, introduce unnecessary or unacceptable hazards, or fail to provide _____________________ 45. U. S. Department of Health, Education, and Welfare. THE INSTITUTIONAL GUIDE TO DHEW POLICY ON PROTECTION OF HUMAN SUBJECTS, DHEW Publication No. [NIH] 72-102, U. S. Government Printing Office, Washington (1971) at 4. 46. Id., citing 21 CFR 130. 37 Compensating for Research Injuries: Chapter 2 adequate safeguards." 47/ Committees were also advised to determine that proper precautions would be taken to deal with emergencies that might develop and, of course, to assure that the informed consent of subjects would be obtained by adequate and appropriate methods. 48/ The Institutional Guide to DHEW Policy was issued in December of 1971. Several months later, Jay Katz's substantial casebook, Experimentation with Human Beings, was published. 49/ It presented the most complete collection of materials on this subject ever compiled, together with commentary and provocative questions about the proper allocation of authority and responsibility for protecting human subjects among those who conduct research, those who fund it, those who review it, those who run the research institutions, the Federal government, professional societies, and the subjects themselves or (in some cases) their parents or legal guardians. Coincident with the renewed regulatory and scholarly interest, an instance of unethical experimentation again became front-page news through articles describing a Public - - - FOR REFERENCE SEE (16bb05.gif) __________ 47. Id. at 5. 48. Id. at 5-7. 49. Jay Katz with assistance of A. M. Capron and E. S. Glass, EXPERIMENTATION WITH HUMAN BWEINGS, Russell Sage Foundation, New York (1972). Compensating for Research Injuries: Chapter 2 38 ments for continuing review, and absence of effective enforcement procedures. 55/ Moreover, the panel noted 56/ No policy for the compensation of research subjects harmed as a consequence of their participation in research has been formulated, despite the fact that no matter how careful investigators may be, unavoidable injury to a few is the price society must pay for the privilege of engaging in research which ultimately benefits the many. Remitting injured subjects to the uncertainties of the law court is not a solution. The panel recommended (among other things) the development of a " 'no fault' clinical research insurance plan to assure compensation for subjects harmed as a result of their participation in research." 57/ From February through July, 1973, the Subcommittee on Health of the Senate Committee on Labor and Public Welfare, chaired by Senator Edward Kennedy, held a series of hearings on human experimentation. Testimony was received regarding a number of incidents (including Willowbrook and Tuskegee) that had heightened public concern about research with human subjects. Bernard Barber reported on a sociological study of biomedical research institutions which showed that the ethical sensitivity of principal investigators was far from adequate and that prior review of experiments was far from universal. Dr. Katz repeated the criticisms and recommendations of the advisory panel's report on the Tuskegee Syphilis Study and his casebook. 58/ His colleague, Alexander M. Capron, raised similar concerns and specifically suggested an indemnification program for all research subjects "to cover all consequences of their participation, including those arising unforeseeably and ______________ 55. Id. at 23 56. Id. 57. Id. at 23-24 58. Hearings before the Subcommittee on Health of the Committee on Labor and Public Welfare, United States Senate, Quality of Health Care-Human Experimenttion, Part 3, March 7-8, 1973, at 1049. 39 Compensating for Research Injuries: Chapter 2 without negligence." 59/ As a result of the hearings, Congress included provisions on the protection of human subjects in the National Research Act, adopted in 1974. The Act not only directed the Secretary of HEW to require establishment of Institutional Review Boards (IRBs) at all grantee institutions, it also created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission was charged with investigating and reporting to the President, the Congress, and the Secretary, HEW, on many aspects of research with human subjects. 60/ At the same time that Congress was creating the National Commission, HEW was in the process of converting its grants administration policy to formal regulations governing the conduct of research with human subjects. Proposed regulations were published in 1973 61/ and final rules were issued in 1974. 62/ For the most part, the regulations codified the policies set forth in the Institutional Guide. One important change, however, was in the applicability of the regulations. Under the old HEW policy, local committee review was required only for research involving risk to human subjects; whether or not the proposed research presented any risk was a matter determined by the principal investigator. Under the new regulations, all research involving human subjects had to undergo review by a local Institutional Review Board (IRB), and it was the IRB that determined whether or not risk was involved, and what the consent requirements should be. _________________ 59. Id. at 845 60. Pub. L. No. 93-348, 55 Stat. 342 (1974). An early version of the bill contained a provision that the Commission "develop a mechanism for the compensation of individuals and their families for injuries or death proximately caused by the participation of such individuals in a biomedical or behavioral research program." (S. 2072, 93rd Cong., 1st Sess., June 26, 1973). 61. 36 FEDERAL REGISTER 27882(Oct 9, 1973). 62. 39 FEDERAL REGISTER 18914 (May 30, 1974). Compensating for Research Injuries: Chapter 2 40 Throughout the early 1970's, a number of other Federal agencies adopted the HEW policies and procedures for the protection of human subjects. By 1977, a review conducted by the staff of the National Commission revealed that of the 20 separate Federal entities (other than HEW) that conduct or support research with human subjects, 19 had formal policies or regulations governing such research. Of those, 17 adopted the HEW standards and procedures to a substantial degree. 63/ Continuing Reservations. Despite all the improvements in regulating the conduct of research, however, concern persisted. No matter how well a project is reviewed, no matter how carefully it is conducted, a chance always remains that someone might be injured. If that should occur, there was still no mechanism to provide compensation. Beginning in 1970, the National Institutes of Health (NIH} submitted a series of compensation proposals to the Secretary, HEW. 64/ Each of the three programs proposed would have provided 40 Historical Perspective compensation (without proof of negligence) for subjects injured as a result of participation in research activities supported in whole or in part by Federal funds. All three, however, failed to gain Departmental backing, reportedly because of one or more of the following reasons: (1) The social and fiscal implications of the proposals had not been assessed; (2) Alternatives to a Federally administered program had not been explored; and (3) The problem was not adequately defined. The next step was taken by the HEW Medical Malpractice Commission which forwarded its report to Secretary Elliot Richardson in January 1973. Although it had not been charged with the responsibility of reviewing human research, the Malpractice Commission included in ______________ 63. National Commission for the Protection of Human Subjects, REPORT AND RECOMMENDATIONS: INSTITUTIONAL REVIEW BOARDS, U. S. Government Printing Office, Washington (1978) at 93 et seq. 64. HEW Secretary's Task Force on the Compensation of Injured Research Subjects Task Force on the Compensation of Injured Research Subjects REPORT, U. S. Department of Health, Education, and Welfare, Washington(1977) (herinafter cited as TASK FORCE REPORT) at III-2. 41 Compensating for Research Injuries: Chapter 2 its report a recommendation that "whenever a grant or other funding is provided by the Federal government for medical research involving human subjects, the grant should include a sum sufficient to provide either insurance or a self-insurance fund in order to provide compensation to any human subject who may be injured in the course of the research. 65/ The Commission added that the same should apply to research that the Federal government itself conducts and to research conducted in the private sector. 66/ In September 1974, prompted by a request by HEW Secretary Caspar Weinberger, the Acting Assistant Secretary for Health [Dr. Theodore Cooper] suggested seven possible approaches for further action on the compensation question. The option selected by the Sec-retary was the creation of a Task Force [composed of HEW staff] to conduct "a detailed study of whether and how to compensate subjects injured in the course of re- search." 67/ One of the reasons for selecting that op- tion was that it had not yet been determined "whether a problem exists which is serious enough to justify the resources needed to develop a compensation mechanism." 68/ The Task Force met 24 times over a period of 18 months and reviewed: (1) a series of reports prepared by experts in law, ethics, and insurance; (2) results of a telephone survey of adverse effects reported [by principal investigators] to have occurred over a three-year period; (3) an analysis of current Federal compensation programs, and (4) responses from the insurance industry to inquiries posed by the Assistant Secretary for Health. 69/ In January 1977, the Task Force published the following recommendations: (1) Human subjects who suffer physical, ______________ 65. Id. 66. REPORT OF THE SECRETARY'S COMMISSION ON MEDICAL MALPRACTICE. U. S. Department of Health, Education, and Welfare (1978) at 79. 67. Id. 68. TASK FORCE REPORT, supra note 64, at III-2. 69. Id. Appendix A. at 9. 70. Id. at II-1. Compensating for Research Injuries: Chapter 2 42 physical, psychological, or social injury in the course of research conducted or supported by the PHS should be compensated if (1) the injury is proximately caused by such research, and (2) the injury on balance exceeds that reasonably associated with such illness from which the subject may be suffering, as well as with treatment usually associated with such illness at the time the subject began participation in the research. (2) The amount of compensation should be commensurate with the "excess" injury as defined above. (3) Subjects participating in PHS-conducted {intramural} research should be included {and should be informed of such inclusion} in the definition of employees within the F.E.C.A., and if injured, should receive such compensation as provided by the Act. (4) Subjects participating in PHS-sponsored (i.e., extramural not PHS-conducted) research should be supplied assurance of compensation {and should be informed of such inclusion} in the definition of employees within the F.E.C.A. and if injured, should receive such compensation as provided by the Act. (5) A Notice of Intent to Issue Regulations should be published as a first step toward implementing recommendation four above and to explore the availability of compensatory assurance. (6) If the provision of such assurance should prove to be infeasible these subjects should be assured protection under the F.E.C.A as would be the partipants of PHS-conducted research detailed in recommendation three above. (7) Research which is PHS-regulated, but not PHS-supported or PHS-conducted, should not be included in the above recommendations. However, we do recommend that the FDA consider legislation which would enable them to require that compensation mechanisms be made available to subjects injured in the course of PHS regulated research. 71/ 71. Id at II-2 43 Compensating for Research Injuries: Chapter 2 The Task Force Report was reviewed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which transmitted a general endorsement of the recommendations to HEW Secretary Joseph A. Califano, Jr., 72/ in June 1977. The Commission subsequently recommended (in its report on institutional Review Boards) that prospective subjects be told whether treatment or compensation would be available if harm occurs as well as whom to contact in such an event. 73/ That recommendation was implemented by DHEW in an "Interim Final Regulation" which took effect January 2, 1979. 74/ In issuing the regulation, the Acting Assistant Secretary for Health noted that: "[S]ince the amendment is being adopted prior to public comment, its scope will be limited to treatment and compensation for physical injury and only to those physical injuries arising from biomedical or behavioral research. 75/ Nevertheless, the research establishment was uneasy. 76/ At least one major university challenged the adoption of a new regulation without opportunity for public review and comment as required by the Administrative Procedures Act. 77/ The Association of American Medical Colleges (AAMC), responding to what it called "great confusion and consternation within the Nation's universities, medical school and teaching hospitals," convened an ad hoc study group to "examine the feasibility of acquiring appropriate insurance coverage and to develop positive suggestions regarding the character of a compensation scheme. " 78/ _______________ 72. Letter from Kenneth J. Ryan, Chairman to Joseph A. Califano, Jr., (June 9, 1977). 73. National Commission for the Protection of Human Subjects, supra note 63, Recommendation 4(f)(iv), at 21. 74. 43 FEDERAL REGISTER 51559 (November 3, 1978). 75. Id 76. William J. Curran, Compensation for Injured Research Subjects: Regulation by Informed Consent, 301 NEW ENG. J. MED. 645 (1979). 77. Letter from Estelle A. Fishbein, General Counsel to Robert Backus (January 17, 1979). 78. Letter from John A. Cooper, M.D., President, AAMC, to Joseph A. Califano, Jr., (June 25, 1979). Compensating for Research Injuries: Chapter 2 44 The AAMC study group concluded that although the Task Force had provided a good conceptual framework, it had not resolved the practical problems involved in the development of a compensation scheme. Therefore, the group recommended that HEW ask its Ethics Advisory Board to study the economic aspects of various possible systems in hopes that it could "resolve the issues in a fashion which takes cognizance of the dynamics of the private insurance system, the needs of academic institutions and the nature of the clinical research enterprise. 79/ Finally, the AAMC asked about the ethical acceptability of a number of limitations it believed insurance companies would impose on any coverage for research-related injuries. The AAMC letter, addressed to Joseph A. Califano, Jr. was received at HEW on June 28, 1979 just a few weeks before Califano was replaced as Secretary of HEW By Patricia R. Harris. In the first week of October, 1979, Secretary Harris sent a memorandum to the Chairman of the Ethics Advisory Board formally requesting that the Board consider whether or not there is an ethical obligation to compensate injured subjects. If so, the Board was then asked to consider whether it would be ethical to impose the limitations that the AAMC suggested might be necessary. 80/ Before the Board could formally agree to consider the compensation question, word came that the Board would be terminated at the end of the 1980 fiscal year. Since it was still in the process of completing two other reports, the Board's Chairman and Vice Chairman decided that it would be infeasible to attempt a study of the eompensation problem in the time remaining, and so advised the Department. 81/ Instead, the Ethics Advisory Board recommended that the President's Commission take up the subject. David Hamburg, Vice Chairman of the Ethics Advisory Board, conveyed this recommendation to the Commission at its first meeting in January 1980 as part of his report on the history and activities of the Board. He explained that the Board had found the compensation issue 79. Id at 6. 80. Memorandum from Patricia Roberts Harris to the Chairman of the Ethics Advisory Board. (October 4, 1976). 81. Memorandum from the Staff Director, Ethics Advisory Board, to the Under Secretary HEW regarding reassignment of the Board's duties (December 21, 1979). 45 Compensating for Research Injuries: Chapter 2 important, but would be unable to undertake the study in the time remaining to it. Before adjourning its first meeting, the Commission voted to undertake a study of the problems surrounding compensation for research injuries. The Study Undertaken by the President's Commission The Commission undertook an investigation of the problems relating to the feasibility of compensating for research injuries that underlay the questions posed by Secretary Harris to the Ethics Advisor, Board. Attempts were made to obtain data from sources on the nature and incidence of research injuries experienced (or likely to be experienced) in the varied kinds of research conducted in the United States. In addition, a series of discus-sions were held with officials of the insurance industry to determine the likelihood that private insurance of appropriate coverage would be available to research institutions. Finally, position papers and scholarly report were also solicited on a number of relevant topics. In an effort to collect data on the nature and incidence of research-related injuries, the Commission requested detailed descriptions and analyses of the experience of two research institutions that have had compensation programs in effect for a period of years. Under contract with the Commission, such reports were prepared by administrators at the University of Washington at Seattle and the Quincy Research Center in Kansas City, Missouri. A similar report describing the insurance program covering biomedical research in Sweden was prepared for the Commission by the physician responsible for assigning a risk factor to each reserch project (from which premium rates are established). A discussion of their findings and conclusions appear in Chapter Four of this Report: the papers are reproduced in the Appendix. The Commission also sought information on the nature and frequency of adverse effects experienced by subjects in research supported, conducted, or otherwise regulated by various Federal agencies. Officials of the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) testified on this subject at the Commission's meeting in May 1980. Information was solicited by mail from approximately twenty other Federal agencies known to conduct or support research with human subjects. Because the Swedish insurance program relies upon a procedure of assigning a risk factor to each research project, the Commission also requested a review of existing literature on adverse effects of twenty selected Compensating for Research Injuries: Chapter 2 46 invasive procedures used in biomedical research (e.g., liver biopsy, bone biopsy, urinary bladder catheteri-zation, lumbar puncture, angiography). The purpose was to determine the extent to which the risk presented to human subjects could reliably be determined in advance and thus to assess the feasibility of setting insurance premiums according to the risk involved in the research projects conducted at a given institution. The findings of that study are also discussed in Chapter Four. Members of the Commission staff held a series of discussions with senior officials of major insurance companies, brokers and trade associations to solicit their cooperation in determining the extent to which private insurance coverage might be available or, alternatively, the advisability of providing for self-insurance through collective insurance pools. The results of those discussions were presented by representatives of the insurance industry in testimony before the Commission and are reflected in Chapter Five and in Appendices P and Q in this Report. The Commission requested further exploration of the ethical arguments for and against the proposition that the Federal government has an oblitagion to provide compensation for research-related injuries. Of particu-lar concern was the extent of the government's obligation (if any) to persons whose participation in research involved testing a new therapy from which they expected to benefit. At public hearings, the Commission heard testimony from the association of American Medical Colleges, the American Society of Clinical Oncology, the Association of American Cancer Institutes and others urging that the Commission not recommend that compensa-tion be provided to patients who participate in research to test new therapeutic interventions from which the subjects expected to benefit. A contrary position was urged by a representative of the DES Registry who, in several appearances before the Commission, described the difficulties of 'DES' daughters in obtaining and paying for medical care necessary to identify early signs of cancer or other abnormal conditions associated with their mothers' ingestion of DES during pregnancy. Although most of the women who took DES in the 1940s and 1950s did so on the advice of their physicians, several hundred women participated in research designed to test the effectiveness of the drug after it was already in general use for the prevention of miscarriage. Those who were research subjects believe they or their daughters should be compensated for the 47 Compensating for Research Injuries: Chapter 2 unanticipated effects of the drug. Other organizations also urged that injured subjects receive compensation. 82/ The Commission noted repeatedly that its task was not to resolve the merits of making payments for past injuries but rather to recommend policy for the future. The Commission also requested reports on legal mechanisms for compensating for personal injury and the extent to which such remedies would be available in the case of research injuries. In addition, health policy analysts were asked to prepare a critical analysis of Federal programs that currently provide compensation or health benefits for certain classes of people (e.g., Federal employees, mine workers suffering from black lung disease, persons with end-stage kidney failure). The latter report examined the difficulties encountered in administering such programs and in containing their cost. Chapter Five containnior officials of major insurance companies, brokers and trade associations to solicit their cooperation in determining the extent to which private insurance coverage might be available or, alternatively, the advisability of providing for self-insurance through collective insurance pools. The results of those discussions were presented by representatives of the insurance industry in testimony before the Commission and are reflected in Chapter Five and in Appendices P and Q in this Report. The Commission requested further exploration of the ethical arguments for and against the proposition that the Federal government has an oblitagion to provide compensation for research-related injuries. Of particu-lar concern was the extent of the government's obligation (if any) to persons whose participation in research involved testing a new therapy from which they expected to benefit. At public hearings, the Commission heard testimony from the association of American Medical Colleges, the American Society of Clinical Oncology, the Association of American Cancer Institutes and others urging that the Commission not recommend that compensa-tion be provided to patients who participate in research to test new therapeutic interventions from which the subjects expected