Defining compensable injury in biomedical research.

Author:Larkin, Megan E.
Position:Abstract through II. Retrospective Nonmaleficence and Distributive and Compensatory Justice as Justifications for Compensation, p. 309-352


Biomedical research provides a core social good by enabling medical progress. In the twenty-first century alone, this includes reducing transmission of HIV/AIDS, developing innovative therapies for cancer patients, and exploring the possibilities of personalized medicine. In order to continue to advance medical science, research relies on the voluntary participation of human subjects. Because research is inherently uncertain, unintended harm is an inevitable part of the research enterprise. Currently, injured research participants in the United States must turn to the "litigation lottery" of the tort system in search of compensation. This state of affairs fails research participants, who are too often left uncompensated for devastating losses, and makes the United States an outlier in the international community. In spite of forty years' worth of Presidential Commissions and other respected voices calling for the development of a no-fault compensation system, no progress has been made to date. One of the reasons for this lack of progress is the failure to develop a coherent ethical basis for an obligation to provide compensation for research related injuries. This problem is exacerbated by the lack of a clear definition of "compensable injury" in the biomedical research context.

This article makes a number of important contributions to the scholarship in this growing field. To begin, it examines compensation systems already in existence and concludes that there are four main definitional elements that must be used to define "compensable injury." Next, it examines the justifications that have been put forth as the basis for an ethical obligation to provide compensation, and settles on retrospective nonmaleficence and distributive and compensatory justice as the most salient and persuasive. Finally, it uses the regulatory elements and the justifications discussed in the first two sections to develop a well-rounded definition of "compensable injury" that is tailored to the biomedical research context. Using this definition, it argues for the development of a first-of-its-kind no-fault compensation system in the United States.

CONTENTS INTRODUCTION I. COMPENSATION SYSTEMS CURRENTLY IN EXISTENCE A. International Compensation Systems 1. Simple Insurance Systems 2. Causation 3. Type 4. Degree 5. Remedy 6. Comprehensive Medical Injury Compensation Systems 7. Lessons from the International Community B. Domestic Compensation Systems II. RETROSPECTIVE NONMALEFICENCE AND DISTRIBUTIVE AND COMPENSATORY JUSTICE AS JUSTIFICATIONS FOR COMPENSATION A. Retrospectivity, Beneficence and Nonmaleficence B. Justice 1. Distributive and Compensatory Justice 2. Reparative Justice C. Pragmatic Reasons for Compensating Research Related Injuries D. Application III. USING ETHICAL JUSTIFICATIONS TO DEFINE "COMPENSABLE INJURY" A. Causation 1. A Theory of Causation a. Causes and Conditions b. Causes and Human Action c. Causes and Principles of Policy 2. A Theory of Causation for Research Related Injuries: The Positive Case 3. Intersection of Causation with the Standard of Care: The Negative Case B. Type C. Degree D. Remedy 1. Economic Remedies 2. Non-Economic Remedies E. Application CONCLUSION INTRODUCTION (1)

In March of 2006, eight healthy young male volunteers in London participated in a first-in-human trial of the novel monoclonal antibody TGN1412. (2) Animal studies indicated that TGN1412 was not likely to have lasting adverse biomedical effects. (3) Nonetheless, within ninety minutes of the drug's administration, the six volunteers randomized to the active arm of the trial suffered headaches, nausea, vomiting, and other symptoms. (4) Within twelve hours of the drug's administration, all six had suffered multi-organ failure and were in critical condition for several days. (5) Many suffered lasting injuries that left them unable to work and dependent on medical care. (6) The TGN1412 trial is a vivid example where research risks that seemed unlikely to occur materialized in a way that severely injured healthy volunteers. (7)

In 1993, five participants that had enrolled in U.S. clinical trials of an experimental Hepatitis B therapy, fialuridine, died as a result of the administration of the study drug. (8) Because the subjects in the TGN1412 were in England, national laws and industry guidelines ensured that they would receive at least some compensation. (9) They ultimately received more damages by alleging negligence on the part of the company running the clinical trial. (10) The fialuridine trial subjects and their families, by contrast, were required to turn to the U.S. tort system "in search of compensation." (11) The Institute of Medicine published a report on the trial that, in part, recommended that a no-fault compensation system for research injuries be developed in the United States. (12) To this date no progress has been made. (13)

Biomedical research provides a core social good that has dramatically improved the quality of life around the world. (14) As one commentator noted, "[e]xtremely 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." (15) Research also provides an evidence base for public health interventions that increase life expectancies and reduce morbidity and mortality. (16) In the twenty-first century, research continues to make progress in reducing transmission of HIV/AIDS, (17) developing innovative therapies for cancer patients, (18) and exploring the possibilities of personalized medicine. (19)

In order to provide society with the benefits of medical progress, the biomedical research enterprise relies on the voluntary participation of research subjects on whom new drugs and interventions are tested and whose normal biological processes are also studied. (20) Depending on the type of intervention being tested and the stage of the research, subjects may be either healthy volunteers from the community or individuals who currently suffer from the disease or condition that the study intervention is intended to alleviate. Research inherently exposes these subjects to risks--both known and unknown--associated with the study intervention, randomization, or research procedures. (21) Unintended harm is, therefore, an inevitable part of the research enterprise. (22) While rare, (23) tragedies like the death in 1999 of eighteen-year-old Jesse Gelsinger from an unforeseen complication in a gene-therapy trial and the death or disability of participants in the fialuridine trial at the National Institutes of Health in 1993, (24) have called national attention to the problem of biomedical research related injuries, but have not led to the creation of a comprehensive framework to provide compensation to those who are injured.

This lack of progress continues in spite of the work of several presidential and other commissions charged with examining the issue of compensation for biomedical research related injuries. (25) The subject was first raised in 1973 when the Department of Health Education and Welfare (DHEW) convened an ad hoc panel to address the ethical questions arising from the Tuskegee Syphilis Study. (26) Four years later, the 1977 DHEW Task Force on the Compensation of Injured Research Subjects concluded that research subjects were entitled to compensation if they suffered injuries that were proximately caused by research participation. (27) This was followed by the report of the 1982 President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, which determined that there was justification for compensating injured research subjects, and that further study on the subject was needed. (28) The 1995 Advisory Committee on Human Radiation Experiments recommended the payment of financial remedies to injured subjects of the World War Il-era human radiation experiments. (29) In 2001, the National Bioethics Advisory Committee found that, as a matter of justice, participants harmed "as a direct result of research should be cared for and compensated." (30) Most recently, in 2011, the President's Commission for the Study of Bioethical Issues released a report entitled "Moral Science," in which it argued that "subjects harmed in the course of human research should not individually bear the costs of care required to treat harms resulting directly from that research," and that the federal government should further study the need for a national compensation system. (31)

As is evident by the strikingly similar conclusions of the 1982 and 2011 reports, policy growth in this area has been staggeringly slow. Many bioethics commissions attribute the lack of progress to a dearth of empirical data on the frequency and severity of research related injuries. (32) Still, other authors have attributed the policy intransigence to "moral gridlock" in the form of disagreement over the ethical justifications for compensation and what those justifications require of a compensation system. (33)

The United States is an outlier among nations in not requiring compensation for research related injuries. (34) The World Medical Association's Declaration of Helsinki states that it is a requirement of ethical human subjects research that, "[appropriate compensation and treatment for subjects who are harmed as a result of participating in research must be ensured." (35) The latest formulation of the Declaration is the first edition to include a requirement for compensation of research related injuries, and it is one indicator among many of a growing consensus among governments, policymakers, and commentators that injured research participants are owed both medical care and financial compensation. (36)

Wide variation remains, however, in the reasons used to justify a requirement for compensation and the mechanisms of...

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