A census of clinical trials conducted under theU.S.exception from informed consent rule

Abstract

Background:The exception from informed consent (EFIC) rule was adopted in 1996, permitting waiver of informed consent for certain emergency research, including trials funded by the U.S. government. The rule requires prospective consent from patients or their legally authorized representative(s) (LAR) if practicable. For those enrolled without consent, the patient or their LAR must be given an opportunity to opt out from continued participation at the earliest opportunity. We sought to census the trials conducted under the EFIC rule to facilitate research to better understand how the rule is being used. Methods:We conducted a multipronged search to identify all trials conducted under the EFIC rule, drawing on reviews, database searches, examination of the FDA's docket, posting an inquiry on the institutional review board forum, and email requests to lead authors of all published EFIC trials and related review articles. We describe the trials, when they were started and completed, and whether they were terminated early. Results:We identified a total of 110 trials as of the end of April 2022: 78 complete, 13 recruiting, seven registered on clini caltr ials.gov but not yet recruiting, five trials that were abandoned before enrolling any subjects, and seven trials in early planning. Nine of the 78 completed trials were pilot or feasibility trials. Of 69 completed full trials, 30 (43.5%) were terminated early. The most common reason for early termination was futility (15 trials, 25.0%) followed by poor recruitment (10 trials, 14.5%). The rate of conduct of trials has been remarkably constant since 2001, with roughly 18 trials started in each 5-year period. Conclusions:We have compiled a census of trials conducted under the U.S. FDA's EFIC rule, the availability of which we hope will stimulate further in-depth data collection and analysis of this set of trials.

Public support for and concerns regarding pediatric dose optimization for seizures in emergency medical services: An exception from informed consent (EFIC) trial

“…The concerns identified in our study, including fear of adverse side effects and loss of parental autonomy, have been reported in previous studies. 11,26,44 Our study found that support for PediDOSE varied by race and ethnicity, health care occupation status, and whether the respondent knew someone with a history of seizures. Previous systematic reviews have had inconsistent results when analyzing the impact of demographic factors on support for EFIC trials, with many individual studies not reporting respondent demographics.…”

“…10 To date, 110 studies have been conducted using EFIC, of which 43 involve prehospital interventions. 11 Studies conducted using EFIC must meet specific criteria and focus on a life-threatening emergent condition where there is no feasible way to obtain prospective consent (Table 1). 10 As part of FDA EFIC regulations, investigators must conduct community consultation to facilitate understanding and promote trust and protection of research participants.…”

“…The first pediatric EFIC study was not conducted until 2007, and only 13% of all approved EFIC studies have involved children. 11 Most studies analyzing the public perception of children participating in EFIC studies have significant limitations, including small sample size, [15][16][17][18][19] homogenous populations, 17,20,21 and being conducted in children admitted to the hospital for critical illness or injury. 4,15,16,19,20 It is, therefore, difficult to conclude how the general population views pediatric participation in EFIC studies and whether these views vary based on demographics.…”

“…To ensure that studies can be ethically conducted in emergency settings, the Food and Drug Administration (FDA) created an “exception from informed consent” (EFIC) process (21 CFR 50.24) in 1996 10 . To date, 110 studies have been conducted using EFIC, of which 43 involve prehospital interventions 11 . Studies conducted using EFIC must meet specific criteria and focus on a life‐threatening emergent condition where there is no feasible way to obtain prospective consent (Table 1).…”

“…Furthermore, most previous EFIC studies have been conducted with adult participants. The first pediatric EFIC study was not conducted until 2007, and only 13% of all approved EFIC studies have involved children 11 . Most studies analyzing the public perception of children participating in EFIC studies have significant limitations, including small sample size, 15–19 homogenous populations, 17,20,21 and being conducted in children admitted to the hospital for critical illness or injury 4,15,16,19,20 .…”