American Journal of Law & Medicine

Recovering from research: a no-fault proposal to compensate injured research participants.

 CONTENTS   I. INTRODUCTION  II. WHY RESEARCH PARTICIPANTS SHOULD BE COMPENSATED      FOR INJURIES      A. The Biomedical Research Enterprise      B. Historical Abuses and Current Research         Participant Protections      C. National Advisory Committees Consider Compensating         Injured Research Participants III. CONTINUED RELIANCE ON THE TORT SYSTEM TO COMPENSATE      INJURED RESEARCH PARTICIPANTS IS MORALLY INDEFENSIBLE      A. Injured U.S. Participants Receive No         Systematic Compensation      B. The Tort System Poses Serious Challenges for All         Research Participants      C. Several Classes of Research Participants Are         Systematically Uncompensated         1. U.S. Participants in Federally Conducted Research         2. International Participants in Federally            Conducted Research         3. International Participants in Privately            Conducted Research            a. Substantive Barriers to Recovery: Corporate Liability               Under the Alien Tort Statute            b. Procedural Obstacle to Recovery: Forum               Non Conveniens  IV. NON-COMPENSATION Is AN IMPEDIMENT TO U.S. RESEARCH      A. The Globalization of Biomedical Research      B. Consensus to Compensate Among Countries         Involved in Research      C. Lack of Systematic Compensation Delays Important         U.S.-Sponsored Biomedical Research   V. THE UNITED STATES SHOULD IMPLEMENT      NO-FAULT COMPENSATION      A. Proposed Solutions         1. Modified Disclosure         2. Mandated No-Fault Compensation System      B. No-Fault Compensation Systems         1. Insurance/Self-Insurance Requirement         2. Specialty Court         3. Compensation Fund         4. Personal Insurance      C. Proposed Parameters         1. Process         2. Research Covered         3. Compensable Injuries         4. Types of Compensation         5. Cross-Border Applicability         6. Implementation      D. Response to Possible Critiques         1. Costs         2. Not Actually a Problem?         3. Now Is Not the Time  VI. CONCLUSION 

National advisory committees have considered the obligations owed to research participants in the event of research-related injuries. These committees have repeatedly concluded that injured research participants are entitled to compensation for their injuries, that the tort system provides inadequate remedies, and that the United States should adopt no-fault compensation. But because the advisory committees have made no concrete proposals and have taken no steps toward implementing no-fault compensation, the United States continues to rely on the tort system to compensate injured research participants.

This Article argues that recent legal developments and a transformation in the global research landscape make maintaining the status quo morally indefensible and practically unsustainable. Recent legal developments exacerbate the longstanding difficulties associated with the tort system as a method of compensation; nearly every injured research participant will have difficulty recovering damages, and certain classes of injured research participants--those in federal research and those abroad--are prevented from recovering altogether, resulting in substantial unfairness. In the past ten years, many of the countries substantially involved in research have mandated systematic compensation. By not mandating compensation, the United States has become a moral outlier and risks having its noncompliant research embargoed by foreign ethics committees, thereby delaying important biomedical advances.

This Article examines alternative compensation mechanisms and offers a concrete no-fault compensation proposal built on systems already in place. The proposed system can be implemented in the United States and countries around the worm to help harmonize various national compensation systems and to more equitably and effectively make those injured by research whole.

I. INTRODUCTION

In the spring of 1993, Participant 10, an asymptomatic carrier of Hepatitis B, enrolled in a National Institutes of Health (NIH) clinical trial of an experimental drug Fialuridine (FIAU), a potential wonder drug for the treatment of Hepatitis B. (1) Three months into the trial, however, researchers suspected something had gone terribly wrong. The first research participant was rushed to the hospital with organ failure. By July 30, five of the ten research participants had died from an unforeseen FIAU toxicity. (2) Patient 10 was among the luckier of the research participants; he was rushed to the hospital, received a liver transplant, and survived--albeit after falling into a coma, spending four months in the hospital, and looking at a lifetime of medication to prevent his body from rejecting the transplant. (3)

The FIAU experiment raised serious concerns within the research community, and commissions were convened to evaluate the trial. A Food and Drug Administration (FDA) committee reached conclusions that were critical of the NIH researchers, (4) but independent panels of the NIH and the Institute of Medicine--an agency within the National Academy of Sciences--cleared the researchers of any wrong-doing, finding that there was "no evidence of negligence or carelessness on the part of the investigators or sponsors." (5)

The FIAU research was not the only biomedical research trial that made headlines, resulted in lawsuits, and prompted increased scrutiny of research. In 1996, Pfizer conducted research on Trovan, a potential blockbuster drug, during an outbreak of bacterial meningitis in Kano, Nigeria. A Washington Post expose (6) published allegations of research abuses during the Trovan trial that formed the basis of the novel The Constant Gardener (7) and a headline-making lawsuit. (8) In 1999, Jesse Gelsinger--an eighteen-year-old enrolled in a gene transfer experiment--died unexpectedly because of the research intervention, resulting in a lawsuit and an undisclosed settlement. (9) In 2010, Professor Susan Reverby uncovered evidence that between 1946 and 1948, U.S. researchers deliberately infected prisoners and mental health patients in Guatemala with gonorrhea and syphilis to test the untreated progression of the diseases. (10) On March 16, 2011, a class-action lawsuit stemming from this research was filed in U.S. court. (11)

These and other cases of research injuries raised important questions about the obligations owed to injured research participants and whether the legal system is the appropriate mechanism to fulfill these obligations. These important questions have not been adequately addressed. A series of national advisory committees convened to consider the obligations owed in the event of research-related injury have concluded repeatedly that injured research participants are entitled to compensation for their injuries, that the tort system provides inadequate remedy, and that the United States should consider some form of no-fault compensation. (12) But because the advisory committees have made no concrete proposals and have taken no steps to implement no-fault compensation, the United States continues to rely on the tort system to compensate injured research participants.

This Article is the first to analyze the developments in the legal landscape and the global research landscape that render continued reliance on the tort system morally indefensible and a significant impediment to U.S. research conducted abroad. Part II provides background on the unique aspects of biomedical research that warrant additional protections for research participants, including no-fault compensation for injuries. Part Ill argues that continued reliance by the United States on the tort system to compensate injured research participants is morally indefensible in light of recent legal developments. The tort system poses challenges unique to research participants that are difficult to overcome and insurmountable for certain classes of research participants, resulting in substantial unfairness.

Part IV argues that the U.S. policy of not compensating injured research participants is an impediment to U.S. research conducted abroad. In the past decade, the research enterprise has become increasingly global, and nearly every country that sponsors, hosts, or conducts substantial amounts of research has required that injured research participants receive systematic compensation. (13) The United States not only is a moral outlier, but also risks having its research embargoed abroad, thereby delaying potential medical advances. Part V argues that the United States should implement no-fault compensation for research-related injuries. After examining a number of solutions, this Article concludes with a proposal that satisfies the moral obligation owed to injured research participants, more equitably and effectively compensates those injured by research at low cost, and can be implemented globally to harmonize various national compensation systems.

II. WHY RESEARCH PARTICIPANTS SHOULD BE COMPENSATED FOR INJURIES

Biomedical research has led to some of the most important medical advances of the past century. Extremely serious and widespread diseases that plagued prior generations--yellow fever, polio, measles, diphtheria, and pertussis--have been almost eradicated through vaccines developed using complex and ground-breaking research. (14) Biomedical research has also given rise to insulin treatment for diabetes, antibiotics for treating a wide variety of diseases, medication for high blood pressure, new surgical techniques, increasingly successful treatments for cancer, and improved treatments for AIDS. (15) As scholars have noted, "the extensive benefits that we have come to expect from medical care undoubtedly depend upon the discoveries of medical research." (16)

But unlike medical care, which treats individual patients, biomedical research creates generalizable knowledge to benefit future patients. Research participants themselves are often only incidental beneficiaries. (17) Because research requires that individuals assume additional risk for the benefit of others, unethical researchers have historically used participants as means to an end without regard for their safety or well-being.

As a result of past research abuses, research today is heavily regulated with increased participant protections. Though generally well-protected throughout the research process, research participants are critically unprotected under U.S. law and international ethical guidelines once research injuries occur. For four decades, U.S. advisory committees have considered and reconsidered whether there is an obligation to compensate research participants who become injured as a result of participating in research. (18) Despite repeated recognition of such an obligation, U.S. advisory committees have made no concrete proposals and have taken no steps to implement systematic compensation. (19)

A. THE BIOMEDICAL RESEARCH ENTERPRISE

Biomedical research is the study of diseases and conditions and the various methods, drugs, and devices used to treat them. (20) Biomedical research shares some superficial similarities with medical care: both biomedical research and medical care aim to improve health through medical interventions, and both biomedical research and medical care are conducted by doctors in medical facilities. (21)

But research, at its core, is fundamentally different from medical care. Medical care is dedicated to providing individual patients with the best treatments for their particular disease. (22) Biomedical research, by contrast, has one primary goal: the creation of generalizable knowledge that can be used to benefit future patients. (23) Research is not conducted primarily to provide the best medical treatment for individual research participants. (24) In fact, many elements of research--placebo-controlled trials, random assignment to treatment arms, restricted flexibility in adjusting dosages, restrictions on using concomitant medications--are contrary to good medical care. (25) Research participants may also undergo a number of procedures to measure study outcomes--including blood draws, biopsies, radiologic scans, and lumbar punctures--that carry burdens or risk without any compensating medical benefit. (26)

The different aims of medical care and biomedical research give rise to different relationships. The doctor-patient relationship is a fiduciary relationship, and patients are entitled to rely on doctors' learned judgments. (27) Doctors, in return, owe patients a duty of care to act in the patients' best interests. (28) As is true of most fiduciary relationships, dependency and trust permeate the doctor-patient relationship. (29) As discussed in more detail in Part II.B, the same is not entirely true of the researcher-participant relationship. The law requires researchers to disclose potential harms of the research, but researchers need not advise potential participants as to whether participation is in their best interests. (30) While trust and dependency may develop in the researcher-participant relationship, these attributes are not the cornerstone of the researcher-participant relationship. (31)

The very nature of research requires that participants assume some risk of harm for the benefit of others, (32) giving rise to a risk-benefit profile that is often different from that of medical care. In providing medical care, a doctor is expected to weigh the risks and benefits of a particular intervention and prescribe a course of action only if the benefits outweigh the risks for that particular patient. (33) The same is not true for research. In accordance with established international ethical guidelines, the risks of research must be favorably balanced by the combined benefit to the individual and to society as a whole. (34) Some research that is considered routine and ethical poses net risk to individual participants. (35)

Given the potentially unfavorable risk-benefit profile, why do people agree to participate in research? The first, and most simplistic, answer is that potential participants may not understand this fundamental difference between research and care. While there is empirical support for this supposition, (36) it is not the full answer. A more complete answer is that individuals participate in research for a variety of reasons, some self-interested and some altruistic. Healthy individuals may choose to enroll in disease-specific research to help or honor a loved one who has battled the disease, or out of gratitude for the medical advances that they have enjoyed due to past research participation. (37) Sick participants may enroll in research to obtain care and treatment otherwise unavailable outside the research context, or to generate knowledge about their disease that benefits future patients. (38) The uninsured may enroll in research to access care or treatment otherwise unavailable to them. (39) Individuals in developing countries may enroll in research because "financial compensation for research participation may exceed participants' annual wages, and participation in a clinical trial may provide the only access to care for persons with the condition under study." (40) Others may choose to participate solely for the payment that they receive for participating. (41) In some egregious historical cases, participants were enrolled unknowingly and unwittingly. (42) These reasons contrast greatly with the primary reason patients participate in medical care: to get better.

This fundamental difference between the goals of medical care and the goals of biomedical research--treating individual patients versus creating generalizable knowledge--manifests itself in different types of relationships (doctor-patient versus researcher-participant), different risk-benefit profiles, and different reasons for participating. As discussed in Part III.B, these distinctions are important in determining what obligations are owed to injured research participants and how the legal system should fulfill those obligations. (43)

B. HISTORICAL ABUSES AND CURRENT RESEARCH PARTICIPANT PROTECTIONS

Although biomedical research is responsible for a vast array of medical advances, biomedical research has also been a means through which horrific abuses have been perpetrated in the name of acquiring knowledge. Nazi doctors conducted appalling research on prisoners without their consent. (44) For four decades, the U.S. government studied the natural progression of untreated syphilis in poor, rural, African-American men in Tuskegee, Alabama, who thought they were receiving free healthcare from the U.S. government. (45) U.S. government agencies conducted a number of experiments to test the effects of radiation on unknowing subjects. (46) And as was recently uncovered, between 1946 and 1948, U.S. researchers infected prisoners and mental health patients in Guatemala with gonorrhea and syphilis to test the progression of the diseases. (47)

Because of the potential for abuse, biomedical research has become a more tightly regulated enterprise over the past half-century. (48) In 1947, the Nazi-era violations gave rise to the Nuremberg Code, (49) the first generally accepted international code governing research with human subjects. Created by a judicial panel with input from physician advisors, the Nuremberg Code set forth the fundamental principle that the "voluntary consent of the human subject is absolutely essential." (50) The Nuremberg Code also set forth other requirements for conducting ethical research, including that research should be able to "yield fruitful results for the good of society," (51) that research "should be conducted to avoid all unnecessary physical and mental suffering," (52) and that the degree of risk "should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment." (53)

Over time, the requirements of the Nuremberg Code came to be considered overly formalistic and inflexible, (54) and the World Medical Association drafted a new set of guidelines. In 1964, the World Medical Association published the Declaration of Helsinki, a statement of ethical principles to guide physicians and other participants in medical research that involves human subjects. (55) Although very much in keeping with the principles of the Nuremberg Code, the Declaration of Helsinki allowed research to be conducted on those incapable of providing informed consent in certain circumstances. (56) The Declaration of Helsinki is widely regarded as a cornerstone of human research ethics. (57)

In the wake of revelations uncovered about the Tuskegee syphilis experiment in 1972, the United States turned its attention to the ethics of biomedical research within its borders and appointed a National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (the "National Commission"). (58) In 1979, the National Commission produced the Belmont Report, which contained a set of ethical principles designed to "provide an analytical framework [to] guide the resolution of ethical problems arising from research involving human subjects." (59) The National Commission's more concrete proposals, including a focus on informed participant consent and prior ethical review by institutional review boards (IRBs), became enshrined in federal regulations that formed the basis of the "Basic Policy for the Protection of Human Subjects" (known as the "Common Rule"), (60) a rule that today governs the conduct of research undertaken by most federal agencies. (61) The Common Rule and the Belmont Report together provide the backbone of the federal oversight system in the United States. (62)

More recently, ethical guidance has focused on the globalization of biomedical research and the concern that research may move to countries where regulation and participant protections are more lax. In 1993, the Council for International Organizations of Medical Sciences (CIOMS), in collaboration with the World Health Organization (WHO), produced the International Ethical Guidelines for Biomedical Research Involving Human Subjects, (63) which includes additional requirements to render international research ethical. (64) Most recently, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, in conjunction with the WHO, promulgated the "Good Clinical Practice" (ICH/GCP) standards with the aim of harmonizing the regulation of clinical trials. (65)

These ethical guidelines and legal requirements have generally coalesced around a number of important protections for research participants. (66) Research must be scientifically valid and able to answer the question it asks; subjecting research participants to risks is otherwise unjustifiable. (67) A trial should be allowed to proceed only if the potential risks to participants are minimized, and if the potential benefits to individual participants and society justify the risks. (68) Each participant must be given sufficient information about the research to "make a voluntary and uncoerced decision whether to participate," though exceptions exist for children and individuals otherwise unable to give consent. (69) Research proposals must be submitted and reviewed in advance by a research ethics committee with authority to prevent trials that do not satisfy these ethical requirements from going forward. (70) And research participants must be allowed to stop participating at any time.

Despite the proliferation of guidance documents, a serious gap in ensuring research participant protection remains. These guidance documents are, for the most part, silent about obligations owed to research participants once injury occurs. (71) Regardless of how tightly regulated the research enterprise is, injuries will still occur; merely informing participants about potential future injuries provides little comfort once injuries do occur. Two organizations--CIOMS and the Institute of Medicine--have taken the lead in recommending that injured research participants receive compensation. (72) But as long as the issue of compensating injured research participants remains unaddressed under U.S. law, a critical gap in research participant protection remains.

C. NATIONAL ADVISORY COMMITTEES CONSIDER COMPENSATING INJURED RESEARCH PARTICIPANTS

For nearly forty years, U.S. national advisory committees have considered whether there is an obligation to compensate injured research participants. These committees have concluded repeatedly that compensating injured research participants is morally required, and that the tort system is inadequate to ensure compensation. (73) But, these advisory committees have put forth no concrete proposals, and have taken no steps to implement systematic compensation. (74) The changing legal and global research landscapes render further inaction morally indefensible and an impediment to the research enterprise.

Although the issue of compensating injured research participants was considered by the U.S. government as far back as 1940, (75) the first national advisory committee to address the issue was a 1973 ad hoc panel created by the Department of Health, Education, and Welfare to review the Tuskegee syphilis study. (76) Several subsequent committees--including the 1977 Department of Health, Education, and Welfare Task Force on the Compensation of Injured Research Subjects; (77) the 1978 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research; (78) the 1982 President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (the "1982 President's Comission"); (79) the 1995 Advisory Committee on Human Radiation Experiments; (80) and the 2001 National Bioethics Advisory Commission (81)--have also considered the issue. The issue of compensating injured research participants was most recently addressed in 2011 by the Presidential Commission for the Study of Bioethical Issues. (82)

These committees repeatedly found a moral obligation to compensate injured research participants, (83) concluding that those "who are harmed as a result of participating in research ought to receive some compensation for their injuries," (84) and that a mechanism to compensate injured research participants "has long been justified on ethical grounds." (85) Alan Weisbard, an attorney who served with the 1982 President's Commission, noted the "obvious intuitive justice and rightness of taking care of those who volunteered to undergo risky procedures for the common good, and through no fault of their own--or of anyone else--were seriously injured in the process." (86) This intuition was best articulated as a justification for compensating injured research participants by the 1982 President's Commission:

    Medical and scientific experimentation, even if carefully    conducted, carries certain inherent dangers. Experimentation has    its victims, people who would not have suffered injury and    disability were it not for society's desire for the fruits of    research. Society does not have the privilege of asking whether    this price should be paid; it is being paid. In the absence of a    program of compensation of subjects, those who are injured bear    both the physical burdens and the associated financial costs. The    question of justice is why it should be those persons, rather than    others, who are to be expected to absorb the financial, as well as    the unavoidable human costs of the societal research enterprise    which benefits everyone. (87) 

These committees, along with bioethics commentators, have argued forcefully that compensating injured research participants is justified by principles of: (I) distributive justice; (2) compensatory justice; (3) internalization of true costs; and (4) the need to maintain trust in the research enterprise. (88)

The first Task Force that considered the issue concluded that compensating injured research participants was a matter of distributive justice, an obligation to distribute the benefits and burdens of research equitably. (89) Prior to beginning a research trial, sponsors of research are able to determine whether the foreseeable benefits of research outweigh the burdens. (90) Research participants are less well-equipped to make this determination. (91) As discussed below, participants are less able to understand the risks and benefits of research and cannot know certain information, e.g., that they will be among the small percentage of research participants who will be injured by the research. Shitting benefits from those who are ensured an appropriate benefit to those who have been unexpectedly and disproportionately burdened by injury satisfies the dictates of distributive justice.

The 1977 Task Force also argued that compensation should be provided as a matter of compensatory justice, an obligation to make whole one you have injured. (92) Compensatory justice requires that an attempt be made to restore injured research participants to their previous condition. (93) The obligation can be satisfied by providing medical care when it is possible to restore injured persons to their previous state, or by monetary compensation when literal restoration is not feasible.

A third justification for compensation is that it forces those conducting research, who can best manage and mitigate the risk of injury, to internalize the true costs of research. The Tuskegee Syphilis Study Ad Hoc Advisory Panel adopted Guido Calabresi's arguments that requiring compensation for research-related injuries "causes the full cost of research in humans to be placed on the research center," which "may cause those involved in the most risky or least useful [research] to consider carefully whether the experiment is worth it, whether it is best done by those who propose to do it, and whether there is an alternative, and safer, way of obtaining approximately the same results." (94) Requiring compensation forces sponsors of research to weigh the true costs of research in determining what research to conduct and what systems to put in place to best manage the associated risks. (95)

Finally, the Institute of Medicine published a report in which it argued that compensating injured research participants fosters trust in the research enterprise. The research enterprise depends upon continued participant enrollment in research. Forcing injured research participants to bear both the medical and financial burdens of research-related injuries could lead to "diminished public trust in the research community," and could lead future generations to refuse to participate in research. (96)

The advisory committees have also addressed the counterargument that compensation may not be required because research participants assume and accept risk through the informed consent process. (97) Under this counterargument, because research participants agree through the informed consent process to accept the articulated risks, mandating compensation protects individuals in ways they have decided is unnecessary. (98)

Advisory committees have disputed any characterization of informed consent as "a waiver of a moral right to compensation." (99) Advisory committees have noted that viewing the informed consent process as a waiver of a right to compensation is an overly legalistic view of the role of informed consent. The purpose of informed consent is to ensure that individuals control whether or not they participate in research and that any decision to participate is voluntary and uncoerced. (100) This voluntary and uncoerced decision to participate should not act as a legal waiver, (101) and, in fact, the federal research regulations expressly provide that research participants cannot be made to waive their legal rights in the informed consent process. (102)

Second, any argument that respect for persons' autonomous decision-making counsels against compensating injured research participants mistakenly conflates participants' willingness to sign informed consent documents without demanding compensation with a preference not to receive compensation. (103) Participants may sign informed consent documents accepting risk and foregoing compensation because those are the terms presented to them. (104) That does not mean that participants prefer to go uncompensated in the event of research-related injuries; it simply means that participants are willing to accept the terms presented, (105) that participants were unaware that they could negotiate for mandated compensation, (106) or that participants did not realize that they may not receive compensation. (107)

Third, research participants may not actually understand the risks and benefits that they accept by agreeing to participate in research. Research risks often include remote possibilities of medical complications, the likelihood and consequences of which may be difficult to assess. (108) Research also carries the potential for unforeseen risks to materialize such that it may be impossible for research participants to consent to all risks of research. (109) Research participants also may misunderstand the benefits that they receive from participating in research. (110) Given that participants may not understand the sacrifices that they make by participating in research, it is important not to foreclose compensation in the event of research-related injuries.

Although most advisory committees have ultimately recommended systematic no-fault compensation, (111) none set forth concrete proposals or took steps toward implementing no-fault compensation, (112) Some committees also recommended a smaller step viewed as the necessary precursor to systematic compensation: (113) collecting empirical data about the necessity and feasibility of compensating injured research participants. (114) Progress has not been made on this front either. (115) Thus, despite recognition for four decades of a moral obligation to compensate injured research participants, the United States only requires that participants be informed as to whether care or compensation will be available. (116) Research participants may end up being forced to choose between bearing the medical and financial costs of research-related injuries alone (117)--in some cases with the help of their insurance (118)--or bringing suit to recover for their injuries in a legal system ill-equipped to ensure adequate protection. (119)

In the past decade, the legal landscape and the global research landscape have changed considerably. In light of these developments, described in Parts III and IV, continued inaction toward compensating injured research participants has become morally indefensible and practically unsustainable.

III. CONTINUED RELIANCE ON THE TORT SYSTEM TO COMPENSATE INJURED RESEARCH PARTICIPANTS IS MORALLY INDEFENSIBLE

The trend in biomedical research over the past half-century has been towards increasing protections for research participants, generally in the form of informed consent and prior review by research ethics committees. Despite strong philosophical justifications for requiring compensation, and recognition of a moral obligation to compensate injured research participants by national advisory committees, the United States has never required that injured research participants receive compensation. (120) Accordingly, most research institutions do not provide compensation, either in the form of free medical care or financial compensation, (121) and research participants who suffer research-related injuries may be forced to bear the medical and financial burdens of research-related injuries alone. (122)

Instead, the United States has continued to rely on the tort system as the primary mechanism through which injured research participants receive compensation. …

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