Examining the Provisions for Research without Consent in the Emergency Setting

Abstract

The Food and Drug Administration recently held a public hearing to elicit feedback on current regulatory approach to research conducted in emergency setting when informed consent is not possible. (1) In addition to hearing, FDA released a draft guidance document on this issue. (2) Of course, doing research without consent is controversial from outset, and bringing attention to it is extremely important. Nonetheless, 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 key pillars of protection for research participants. It has been a decade since FDA issued its Rule permitting some research in emergency setting to forgo informed consent. (3) Briefly, rule includes requirements for institutional review board approval of proposed research; procedures for informing research participants or their legally authorized representatives about 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 IRB's findings that proposed subjects are in a life-threatening situation, that available treatments are unproven or unsatisfactory, and that evidence is needed to establish safety or efficacy of proposed intervention. In addition, IRB must find that obtaining consent is not feasible, a prospect of direct benefit to subjects exists, research is not practicable without waiver, and a process is outlined for contacting legally authorized representatives about research and for informed consent. Finally, rule sets out requirements designed to give participants additional protection: community consultation regarding proposed research, public disclosure about research, a data safety and monitoring committee to oversee research, and provisions for contacting family members. According to FDA, twenty-one studies to date have been or are being conducted under Final Rule. (4) Some of this research has been relatively uncontroversial and has resulted in obvious improvements in treatment in emergency setting. For example, a trial demonstrating utility of portable defibrillators in public spaces came and went with little comment. In contrast, PolyHeme trial, which involves testing a blood substitute, has created considerable controversy in popular and professional literature, even inviting Congressional inquiry. Clearly time is right to learn from these experiences. The speakers at 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 emergency setting was needed. One suggestion was to establish a central body that might be similar to Recombinant DNA Advisory Committee (commonly known as the RAC), which provides input into oversight of gene transfer research. On this approach, national board might advise investigators and local IRBs. Alternatively, a national IRB similar to that being used by National Cancer Institute to review large group multicenter trials might simply obviate need for multiple local reviews. …