_______________________________________________________ President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research Morris B. Abram, MA., J.D., L.L.D., Chairman New York, N.Y. George R. Dunlop. MD* Daher B. Rahi, D.O.* University of Massachusetts St. Clair Shores, Michigan Renee C. Fox, Ph.D., D.H.L. Anne A. Scitovsky, M.A. University of Pennsylvania Palo Alto Medical Research Foundation Mario Garcia-Palmieri. 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.þ S.T.M, Ph.D. Colorado Springs, Colorado University of California, San Francisco Charles J. Walker, M.D. Nashville, Tennessee Donald N. Medearis, Jr., M.D. Harvard University Carolyn A. Williams, Ph.D. University of North Carolina Arno G. Motulsky, M.D. Chapel Hill University of Washington _______________________________________________________________ *Sworn in February 11, 1982 Term expired February 11, 1982 þ Sworn in March 12, 1982 Staff Alexander M. Capron. L.L.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.B.A. Presidents Commission Kathryn Kelly, M.S. Commonwealth Fellows and Susan Morgan Student Interns Marian Osterweis, Ph.D Joshua Abram (1980) Renie Schapiro, M.P.H. Deborah Blacker (1980) Daniel Wikler, Ph.D. Cheryl Cooper (1980) Jeffrey Katz (1981)Research Assistants Ruth Oratz (1981) Michelle Leguay Henry S. Richardson (1981) Jeffrey Stryker Jennifer Seton (1980) David Tancredi (1981) Consultants William Thompson (1981) Bradford H. Gray. Ph.D. Mindy Werner (1982) Dorothy Vawter Table of Contents Volume Two: Appendices Part I: Social and Philosophical Perspectives 1 A. A Social Perspectives on Compensation for Injured Research Subjects (Judith P. Swazey and Leonard Glantz) 3 Introduction 3 The Protection of Human Subjects 4 The Present Climate of Concerns about Compensation 7 Research and Human Subjects 12 Research and Gift-Exchange 16 Who Are Research Subjects Like? The Pandora's Box Argument 17 B. Compensating Research-Related Injuries: Ethical Considerations (Holly M. Smith) 19 The Varieties of Moral Status 20 Possible Reasons for Action 21 Consent 23 Arguments in Favor of Compensation 24 Practical Concerns 30 Conclusion 39 C. Consent and Compensation (Bernard R. Boxill) 41 Introduction 41 The Nature of Compensation 42 The Effect of Consent 49 The Ethical Justification for Compensating Research Subjects 53 Part II: Data on Risks of Biomedical and Behavioral Research 57 D. Demographic Notes on the Subjects of Biomedical and Behavioral Research (Robert A. Cooke) 59 The Sample and Weighting of Projects for the National Commission 59 The Sample and Weighting of Projects for the President's Commission 60 Summary of the Analyses 61 iv E. Risk of Injury Associated with Twenty Invasive Procedures Used in Human Experimentation and Assessment of Reliability of Risk Estimates (Mary Harvey and Robert J. Levine) 73 Objective 73 Materials and Method 75 Results 76 Factors Influencing Reliability of Risk Estimates 144 Discussion 145 Part III: Legal Perspectives 173 F. Perspectives on Compensating Accident Victims (John G. Flemming and Stephen D. Sugarman) 175 Introduction 175 Negligence 176 Liability Without Fault 187 Tailored Compensation Plans 191 General Compensation Plans 198 G. Some Legal Perspectives Toward Personal Injury Compensation (Marshall S. Sharpo) 205 Legal Doctrine 205 Some Functional Application of Tort Law 219 Relevant Statutory Background of Tort Law 228 K. On the Compensation for Injured Research Subjects in Sweden (Harry Bostrom) 309 Introduction 309 Incidence of Injuries 311 Compensation Program 314 L. Materials Concerning Compensation of Subjects Injured in Research: University of Leiden, The Netherlands (E.L. Noach) 323 Introduction 323 Insurance 324 Part V: Possible Compensation Mechanisms 335 M. Existing Federal Programs as Models for Compensation of Human Subjects (Stanley B. Jones) 337 Purpose 337 The Characteristics of the Compensation Program for Research Subjects Proposed by the 1977 HEW Secretary's Task Force 338 Relevant Experience of Existing Federal Programs 340 Suggestions for a Compensation Program Research Subjects 358 N. Arbitral Processes for a Program to Compensate Injured Research Subjects (Irving Ladimer) 373 Executive Summary 373 Introduction 375 Issues Requiring Determination in a Compensation Program 376 Arbitral Processes and Formats Available 382 Selecting Arbitration: Checklist for Establishing an Appropriate Plan 395 Recommendations 406 O. Interim Report on Private Research Injury Insurance (George K. Bernstein) 413 P. Compensation for Injured Research Subjects: Funding Mechanisms (Thomas S. Chittenden) 423 Q. Statement of the American Insurance Association 429 R. Risk Management and Insurance (University Risk Management and Insurance Association) 437 Introduction 437 Survey Regarding Adverse Effects 438 Elements of a Compensation Program for Adverse Effects of Human Subjects Research 440 Conclusion 445 S. Model Compensation Program Developed by Commission Staff 449 Plan I 454 Plan II 460 Plan III 465 Part VI: Testimony and Correspondence Received by the Commission 471 T. Written Materials Submitted to the Commission 473 U. Individuals Who Presented Oral Testimony Only 509 ____________________________________________________ Social and Philosophical I Perspectives President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavorial Research The Honorable Richard (ILLEGIBLE) Secretary, Department of Health and Human Services Washington, D.C. 20202 Dear Mr. (ILLEGIBLE) On behalf of the President's Commission for the study of Ethical Problems in medicine and biomedical and behavorial research, I am pleased to transmit our Report on Compensating for Research Injuries. As you know, this study was not within the Commission's statutory mandate. We embarked upon it at the (ILLEGIBLE) of your Department's Ethics Advisory Board and with the support of your predecessor, Patricia Roberts Harris, is hoped that we could resolve a problem of considerable complexity that has been a matter of concern within the Department, and the Federal government generally, for some years. Other individuals and groups who have examined this issue, (ILLEGIBLE) in HEW [ILLEGIBLE TEXT) Compensation plans with varied features could be tried out at several research institutions, including the Clinical Center at the National Institute of Health, while docs were also being gathered at other institutions without compensation programs. Through this two-part effort to gater data, it should be possible both to assume the apparent overall magtitude of research injuries and to determine the effort of a program's existance on the frequency and severity of the injustice reported. The objectives of the employment and details about the programs that could be tested are set forth in this Report and its separate Appendix volume, which contains additional supporting material. Although we have not been able to write the last work on the subject, we hope to have advance the discussion. Final decisions on this matter, we believe, are best left to your Department as part of its statutory (ILLEGIBLE) for the administration of Federal support for biomedical and behavioral research. Other Federal research agencies, as well as the private (ILLEGIBLE) of research with human subjects, will doubtless be guided by your experience in assessing possible (ILLEGIBLE) for compensation programs. Sincerely yours, Sgd. Morris B. Abram Chairman Table of Contents Volume One: Report Summary and Conclusions 1 The Question at Issue 2 Alternative Responses to Inconclusive Data 2 The Recommended Experiment 4 The Format of the Report 4 Part I: How Did This Issue Arise 7 Chapter 1: Introduction to the Social and Cultural Setting 9 Roles and Relationships in Human Experimentation 11 The Role of Biomedical and Behavioral Research 11 The Role of the Research Subject 13 The Relationship of Subjects to the Research Enterprise 15 The Relationship of Subjects to the Beneficiaries of Research 16 Risk (and Risk-Spreading) as a Social Problem 17 Research Injuries and the Larger Social Context 19 The Basis for Public Policy 22 Social Responsibility and Individual Consent 22 Administrative Practicability and the Plight of the Helpless 22 Chapter 2: Historical Perspectives 25 Reliance on Codes and Consent (1945-1966) 25 Outside Encouragement for Self-Regulation 25 Apparent Problems in a Mighty Enterprise 30 Prior Review and Limitations on Risk (1966-present) 33 Strengthening Regulations 35 Continuing Reservations 39 The Study Undertaken by the President's Commission 43 Part II: Do Deserving Subjects Not Receive Compensation? 47 Chapter 3: The Ethical Basis for Compensation 49 A Question of Justice 50 The Argument from Fairness 50 The Gift of Security: Consenting Subjects as Free Agents 53 Fairness vs. Consent 56 Additional Reasons for Compensation 60 Appropriate Regard for Patient-Subject's Well-Being 60 Public Conceptions of Justice 61 Obligations to Subjects in Therapeutic Research 61 Conclusions 63 Chapter 4: The Nature and Extent of Research-Related Injuries 65 Longitudinal Institutional Studies 67 General Research Program: University of Washington, Seattle 67 Nontherapeutic and Therapeutic Drug Testing Quincy Research Center 69 Nontherapeutic Drug Testing: Michigan State Prison 71 Broadly Based Sources of Data 71 Government-Reported Incidence of Harm 72 Prospective Approach 73 Number of subjects 74 Subject Characteristics 74 Risks of Research 77 Conclusions 79 Chapter 5: Existing Remedies and Their Limitations 81 Negligence 83 Requirements for, and obstacles to, Recovery 84 Critique of Negligence as a Remedial Mechanism 88 Strict Liability 90 Roots in History and Politics 90 Applicability to Research Injuries 91 Critique of Strict Liability 95 Nonfault Approaches 97 Government Compensation Programs 97 Insurance Mechanisms 98 Part III: What Should Be Done? 101 Chapter 6: Conduct an Experiment 103 Specific Aims of the Experiment 108 Research Plan 107 Methodological Issues 108 Sample Selection 108 Sample Size 110 Duration of Study 110 Costs 110 Standards for Evaluating the Desirability of Instituting a Compensation Program 111 Chapter 7: Consider Various Features of Nonfault Insurance Programs 113 Existing Governmental Programs as Models 114 F.E.C.A. and other Workers' Compensation Programs 115 Veterans Benefits 118 Vaccine and Immunization Programs 119 Evaluation of Governmental Alternatives 120 Insurance Mechanisms as Models 122 Institutional Private Insurance 122 Institutional Self-Insurance 123 Collective or Pooled Insurance 124 Evaluation of Insurance Alternatives 125 Objectives of a Compensation Program 126 Basic Elements of a Compensation Program 128 Variables to be Included in the Experimental Design 129 Scope of Covered Research 129 Government involvement 129 Type of research and IRB review 131 The problem of therapeutic research 132 Eligibility for Benefits 135 Subjects of covered research 135 Nontrivial bodily injuries 136 Causation 138 Standards of Conduct 139 Time for Making a Claim 140 Nature and Extent of Benefits 141 Limitation on Benefits 144 Pain and suffering 144 Punitive damages 145 Legal fees 145 Ceiling on Benefits 145 Offset for Recoveries from Collateral Sources 146 Relation to Alternative Legal Remedies 147 Resolution of Disputes 148 Financing Mechanisms 149 _____________________________________________________ Table Table 1. Demographic Characteristics of Biomedical and Behavioral Research Subjects 75 Figures Figure 1. Subjects Participating in Research (By Percent of Projects) 76 Figure 2. Distribution of Therapeutic/ Nontherapeutic Projects (By Type of Institution) 77 Figure 3. Percent of All Subjects Exposed to Four Invasive Procedures Most Frequently Used in Research 78 _____________________________________________________ Volume Two: Appendices, which contains Studies prepared for the Commission, material submitted for its consideration and possible compensation plans. Summary and Conclusions The origin of this study by the President's Commission was a suggestion conveyed by Dr. David Hamburg, the Vice-Chairman of the Ethics Advisory Board in the Department of Health, Education and Welfare (HEW), when he testified at the Commission's first meeting in January 1980. Dr. Hamburg explained that the Board would be unable, prior to its demise in September 1980, to offer the Secretary the advice she had requested concerning the advisability of the recommendations for a program to compensate subjects injured in research that had been submitted to the Secretary by an HEW Task Force in 1977. Like virtually all committees and individuals who had studied the subject, the HEW Task Force had concluded that people who are harmed as a result of participating in research ought to receive some compensation for their injuries. The Secretary informed the Commission that she would provide support for necessary studies. The more deeply the Commission looked into the subject, the more difficult it became to provide a simple reply to the questions originally posed by the Secretary. The Commission has concluded that it would be ethically desirable to remedy as a matter of course any harm suffered by subjects as a direct consequence of the added risks of participating in research. Yet even if it is ethically desirable for compensation to be provided, it does not follow that the Federal government has an ethical obligation to establish or to require a formal compensation program in all research projects supported or regulated by the government. For the latter, it is necessary to demonstrate the existence of unmet need and to weigh that need against other needs in the public arena. Compensating for Research Injuries The Question at Issue In this Report the Commission seeks the answer for the following questions: Are subjects who deserve compensation for research injuries not receiving it?1 [In other contexts the term "compensation" connotes payment for services rendered. In this Report the term is used solely to indicate payments made to redress an injury after the fact; payment for the time and trouble of participating in research is termed "remuneration."] In light of the many earlier examinations of the subject of research compensation, the Commission began with the hypothesis that the answer to this question was "yes." If the answer to the question were in the affirmative, the Commission understood its further task to be the design of a compensation plan that would respond to the needs uncovered in its study. It is apparent that the hypothesis that the Commission set out to test actually encompasses issues of both an empirical and a philosophical nature. Specifically, the original question reflects several underlying questions: (1) What does one mean by "deserve compensation"? (2) How many such subjects are injured each year in research, and how severely? and (3) which of these subjects receive no compensation at present, and why? The Commission has found itself more able to answer some of these questions than others. The question of what ought to be encompassed within " compensation for research injuries" and the question of who deserves such compensation are fully addressed in this report. In investigating the empirical issues, however, the Commission was able to expand upon the existing knowledge but unable to find data sufficient to resolve fully the questions of the extent of present injuries and of present redress. The absence of data on injuries is not, needless to say, the same as data on the absence of injuries. Alternative Responses to Inconclusive Data From this outcome several conclusions might be drawn. One might conclude that what is needed if further data gathering about the existence of research injuries. Indeed, in its First Biennial Report on Protecting Human Subjects, submitted to the President and Congress in December 1981, the Commission recommended that investigators conducting Federally funded research routinely submit data on the number of subjects involved in such research and the number and extent of injuries suffered, on an annual basis. From such data, as well as supplementary inquiries, it ought to be possible to provide a better answer to the empirical questions addressed in this report. Summary and Conclusions 3 There are, however, reasons to doubt that this approach will provide sufficient data. In the absence of a formal compensation mechanism there is good reason to doubt that subjects or investigators will accurately report the occurrence and extent of injuries suffered by subjects in research. Furthermore, it is only through experience with compensation programs that two of the most difficult questions that are always raised in opposition to such programs can be answered: first, what are the administrative costs of the programs, including the costs of distinguishing between injuries deserving compensation and those claims that do not deserve to be compensated ( and that, it is assumed, would not be asserted in the absence of a compensation program)? Second, do feasible means exist to differentiate harm to subjects in therapeutic research that results from research procedures from harm that flows from the medical intervention being treated?2 [The term "therapeutic research" is used loosely to describe any experimental or innovative steps taken as part of an attempt to treat subjects suffering from disease (in comparison with "nontherapeutic research," which employs subjects not affected by the disease being studied). The Commission uses the term to mean research to evaluate practices or procedures that are intended to provide, or that have some reasonable possibility of providing, therapeutic, diagnostic or preventive health benefits to subjects. Such research therefore involves two parts: (1) the practice or procedure that is being evaluated and (2) any nonbeneficial research procedure that is unnecessary for a subject's own welfare and is performed solely as an aid to the research process. ] Clearly, an experimental trial of one or more compensation program is more likely than simply collecting data in the absence of such programs to provide the necessary information for the formulation of appropriate public policy. Yet that approach would entail greater costs, since an experiment to gather the data would involve the expenditure of time and money in design and execution. At a time when the Federal funds available for biomedical and behavioral research are not keeping up with the rate of inflation, there are more than the usual reasons to question any suggested expenditures in new areas. It may well be, therefore, that those with responsibility for the decision in the Department of Health and Human Services (HHS) will conclude that an experiment of the sort set forth in this Report is not justified at this time. On balance, however, the Commission recommends that such an experiment be undertaken, because in the absence of such an investigation of the need for, and feasibility of, compensation programs, it believes that policymakers will be in no better position to answer the questions addressed by this Report in five years than they are today. Compensation for Research Injuries The Recommended Experiment 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 time has come to determine the wisdom of those suggestions. The failure to resolve the issue not only exposes subjects of research to a possible wrong, it 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 attempt to conquer disease and to relieve human suffering. The formal ethical standards and individuals 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 though 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 further to reduce the risk of unremedied injury to subjects and to avoid the occurrence of events that might needlessly tarnish the reputation of research. Accordingly, the Commission recommends that the Secretary of Health and Human Services conduct a small-scale experiment in which several institutions would receive Federal support over three to five years for the administrative and insurance costs of providing compensation on a nonfault basis to injured research subjects. At different institutions the features of the compensation plan could be varied (i.e.. the level of benefits provided; means of determining causation; whether nonphysical injuries would be covered; whether certain injuries arising in therapeutic as well as nontherapeutic research would be covered; etc.). Information derived such variation, as well as from the experience of comparable institutions without research compensation programs, should permit HHS to determine not only the need for a full-scale program, if any, but also the format and auspices that appear best suited to achieve the desired results. The Format of the Report The first part of this Report explores the origin and context of the issue of compensating for research injuries. The first chapter introduces such social and cultural factors as the relationship of subjects to the research enterprise and concerns about cost-spreading in a risk-conscious society. Chapter Two places the present study into the setting of research regulation since World War II. During this period, proposals for injured subjects' compensation were made in many contexts but seldom were accompanied by more than a rough sketch of the details of a plan of implementation. Part two delves into the several parts of the basic question: Are injured subjects who might deserve compensation not receiving it? Chapter Three examines the ethical theories--sometimes competing and sometimes complementary--that shed light on the question of subjects' deserts. In the case of injuries to voluntary, informed subjects, a strong moral claim for recompense does not emerge. Whether such ideal subjects actually exist is a serious ethical issue, and one that cannot be ignored in policy formulation. It would, moreover, appear to be morally preferable, on grounds both of fairness and of gratitude, not to insist that subjects waive all claims for redress as part of consenting to research, particularly nontherapeutic research. Chapter Four analyzes the existing data on the incidence and severity of research injuries. While data from existing programs suggest that nonfault insurance is an efficient and inexpensive means of providing recompense for research injuries, there also appear to have been few injuries at the handful of institutions that already have formal compensation programs. Why are other injured subjects not guaranteed recompense? In Chapter Five, existing legal rights and remedies are examined. The limitations of negligence and strict liability as bases for recovery at law arise from the restricted nature of the legal duties owed to the subjects, the waiver of rights implied by consent, and the difficulty of proving causation. Through this examination, the Commission arrives at a partially affirmative answer to the question of whether or not there is an unmet obligation to injured research subjects. Available information does not, however, provide the definitive basis for a recommendation to undertake a compensation program, through Federal sponsorship or under the mandate of Federal regulations. Instead, in Part Three of this Report, the Commission sets forth the issues that could be resolved through a "social policy experiment." Since the request for this study came from what is now the Department of Health and Human Services (HHS), which is the major Federal sponsor of biomedical and behavioral research with human beings, and since the Commission has previously recommended that the Department become the lead agency in overseeing regulations on the protection of research subjects, the Commission believes that the experimental compensation program should conducted under the aegis of HHS.