Waived Consent for Emergency Research

Norman Fost^ The voluntary consent of the human subject is absolutely essential.' INTRODUCTION Contrary to the first principle of the Nuremberg Code, the voluntary consent of the human subject is neither necessary nor sufficient for ethically and legally responsible research in the United States. That it is not sufficient has been well argued by Robert Burt2 and others. We would not say that the central problem of the Nazi experiments was their failure to obtain informed consent.3 Nor would the presentation of signed and witnessed consent forms change anyone's view on the moral justification for the experiments.4 For related reasons, institutional review boards (IRBs) sometimes reject or defer protocols for paternalistic or various other reasons, arguing that clinicians should not allow patients to consent to be subjects in a study.5 It has also been recognized that the subject's informed consent is not always necessary for ethically acceptable research. The Declaration of Helsinki6 and the U.S. Department of Health and Human Services (DHHS) regulations acknowledge that appropriate representatives may consent on behalf of a subject7 and that in some circumstances consent may be waived altogether.8 Fueled by advances in cardiopulmonary resuscitation and the treatment of severe brain injury, interest has accelerated in conducting clinical trials on patients who are unable to consent because of their medical condition, and whose condition required initiation of treatment before an appropriate representative could be contacted to provide surrogate or proxy consent. In the United States, an investigator seeking to conduct research on such patients was caught between the Scylla and Charybdis of two conflicting sets of regulations. The Food and Drug Administration (FDA) allowed for a waiver of consent for interventions that were necessary to save the life of the patient.9 To waive consent, the DHHS regulations required, inter alia, that the experimental treatment present no more than minimal risk.io The FDA's emergency guideline, in contrast, required, that the research hold out the prospect of direct benefit to the patient.lt The combination of these rules were considered by many to preclude placebo-controlled clinical trials on patients unable to consent, because a placebo is rarely necessary to save the life of a patient,l2 and DHHS regulations precluded experimentation, regardless of its possible life-saving implications, for all but the most trivial interventions.13 As a result, innovative therapies either have not been developed, or have been tried without the benefits of well-designed trials, often resulting in longdelayed discoveries that innovative approaches were unacceptably toxic, inefficacious or both.l4 In response to these concerns, a coalition of critical care investigators, with the endorsement of many leading medical professional organizations, proposed a change in the federal rules that would allow for the expansion of the conditions under which consent could be waived in emergency research.15 Following a conference sponsored by the National Institutes of Health (NIH) and the FDA,I6 proposed regulations were published,l7 and, after review of extensive comments, a final rule announced.18 This Article reviews the history of waivers for informed consent in research involving human subjects; legal and regulatory aspects of the current rule; the ethical issues involved; and issues that will need to be addressed as the rule is applied in clinical studies. II. RECENT HISTORY OF REGULATIONS REGARDING WAIVED CONSENT The World Health Organization's Declaration of Helsinki, while affirming the importance of consent from the subject,l9 departed from the Nuremberg Code's absolutism by acknowledging exceptions. First, it acknowledged that incompetent patients can be research subjects if consent is obtained from a "responsible relative. . in accordance with national legislation. …