Examining the Provisions for Research without Consent in the Emergency Setting

The Food and Drug Administration recently held a public hearing to elicit feedback on the current regulatory approach to research conducted in the emergency setting when informed consent is not possible.¹ In addition to the hearing, the FDA released a draft guidance document on this issue.²

Of course, doing research without consent is controversial from the outset, and bringing attention to it is extremely important. Nonetheless, the treatment of patients who suffer from a range of emergent conditions—cardiac arrest, profound stroke, and trauma, for example—is inadequate, and research is clearly necessary to identify safe and effective therapies for such conditions. Unfortunately, those who suffer them are typically unable to provide consent, which eliminates one of the key pillars of protection for research participants.

It has been a decade since the FDA issued its "Final Rule" permitting some research in the emergency setting to forgo informed consent.³ Briefly, the rule includes requirements for institutional review board approval of proposed research; procedures for informing research participants or their legally authorized representatives about the research when feasible; provisions for recordkeeping; processes related to FDA oversight (such as "investigational new drug" and "investigational device exemption" applications); and responsibilities for unapproved research. The requirements for IRB approval include that an independent physician corroborate the IRB's findings that the proposed subjects are in a life-threatening situation, that available treatments are unproven or unsatisfactory, and that evidence is needed to establish the safety or efficacy of the proposed intervention. In addition, the IRB must find that obtaining consent is not feasible, a prospect of direct benefit to the subjects exists, the research is not practicable without the waiver, and a process is outlined for contacting legally authorized representatives about the research and for informed consent. Finally, the rule sets out requirements designed to give participants additional protection: community consultation regarding proposed research, public disclosure about the research, a data safety and monitoring committee to oversee the research, and provisions for contacting family members.

According to the FDA, twenty-one studies to date have been or are being conducted under the Final Rule.⁴ Some of this research has been relatively uncontroversial and has resulted in obvious improvements in treatment in the emergency setting. For example, a trial demonstrating the utility of portable defibrillators in public spaces came and went with little comment. In contrast, the PolyHeme trial, which involves testing a blood substitute, has created considerable controversy in the popular and professional literature, even inviting Congressional inquiry. Clearly the time is right to learn from these experiences.

The speakers at the recent FDA hearing covered a broad range of issues, but their comments clustered around three broad themes: community consultation, national review, and types of research.

The speakers described a range of views and stories about community consultation. Some expressed frustration over consultation efforts that did not involve a substantial number of participants, and others over a lack of clarity about how information might be used to protect subjects' rights and welfare.

Commentators generally agreed that some type of national review for research in the emergency setting was needed. One suggestion was to establish a central body that might be similar to the Recombinant DNA Advisory Committee (commonly known as "the RAC"), which provides input into the oversight of gene transfer research. On this approach, the national board might advise investigators and local IRBs. Alternatively, a national IRB similar to that being used by the National Cancer Institute to review large group multi-center trials might simply obviate the need for multiple local reviews. In short, specific proposals differed, but one way or another, commentators seemed interested in creating an entity that would involve review at the national level because of local IRBs' potentially limited expertise and experience with research in emergency settings. Of course, implementing such a program will be feasible only if ways can be found to incorporate local attitudes into the review and oversight process.

The Final Rule has a one-size-fits-all approach to research protocols that seek an exemption from the requirement to obtain consent, but not all research in...