A 20-year Review: The Use of Exception From Informed Consent and Waiver of Informed Consent in Emergency Research.

BACKGROUND

Due to the acuity and time-sensitive needs of their clinical condition, patients presenting with certain emergent pathologies may lack capacity to provide meaningful prospective informed consent to participate in clinical research. For these reasons, these populations have often been excluded from research investigations. To mitigate this, regulations allowing exception from informed consent (EFIC; 21 CFR 50.24) or waiver of informed consent (WIC; 45 CFR 46.101) were developed in 1996. The purpose of this study was to identify trends in the utilization of EFIC and WIC in emergency research. We also sought to describe the disclosure of necessary prestudy regulatory requirements and justification for the use of EFIC/WIC as reported in completed EFIC/WIC clinical trials.

METHODS

This study is a review of 20 years of published trials using EFIC or WIC as the primary method of patient consent. Studies were identified using a MEDLINE search; ClinicalTrials.gov; queries to emergency and resuscitation researchers, research directors, department chairs, and principal investigators of acute care research networks; clinical review papers; and a query of the Federal Drug Administration (FDA) docket. All eligible studies were reviewed by three investigators and study data of interest were abstracted. Data are presented descriptively.

RESULTS

We identified 45 potentially eligible studies; 11 were ongoing (with no data yet available), four were completed (with no publications or data available), and two did not use EFIC or WIC. Of the remaining 28 studies, 24 (86%) used EFIC and four used WIC. The most common pathologies under study were cardiac arrest (10), hemorrhagic shock (six), and traumatic brain injury (five). Completion of the prestudy regulatory requirements was reported as follows: FDA investigational new drug/investigational device exemption application (for FDA regulated studies; 14, 50%), community consultation (13, 46%), public disclosure (10, 36%), and opt-out procedures if requested by the institutional review board (seven, 25%). The justification of the need for the use of EFIC or WIC in the reported clinical trial, as defined as mention of at least one of the eight established criteria, was described in the text of 13 (46%) publications.

CONCLUSIONS

Since their implementation in 1996, the EFIC/WIC regulations have allowed progress in research aimed at determining optimal care for devastating life-threatening conditions. However, consistent and rigorous report of regulatory prestudy requirements and justification of the use of EFIC/WIC is lacking in clinical trial publications or on websites such as ClinicalTrials.gov. Since research without consent is an ethically sensitive issue and not widely understood, better justification of its needs within the presentation of the research itself may educate the general medical community and also reduce concerns about whether or not the regulations are being properly applied.