The History and Policy Evolution of Waivers of Informed Consent in Research

Journal of Empirical Research on Human Research Ethics

2022

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Impracticability is an ethical standard for waiver of informed consent in research. We examine how well the criterion of impracticability appears to have been fulfilled in a set of 36 completed randomized controlled trials (RCTs) that secured consent from some subjects or LARs and employed waivers to enroll others. These trials were identified among 155 RCTs using waivers of consent in a convenience sample drawn from 7 systematic reviews. Recruitment data were available for 19 of the 36 trials, revealing an average of 41.6% of subjects (range 0.2–98.7%, 95% CI: 24.8–58.4%) were enrolled without consent. Six trials enrolled less than 10% of subjects without consent and an overlapping set of 9 trials sought consent from all subjects or LARs at some sites while waiving consent at other sites. We question whether these trials were practicable without waivers and identify issues for consideration by investigators and ethics review boards.

Section: Discussionmentioning

confidence: 99%

Practicalities of Impracticability: An Interim Review of Randomized Controlled Trials

Dhamanaskar

Feldman

Journal of Empirical Research on Human Research Ethics

2022

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“…1,2 In the early 1990s, with increasing attention to the need to conduct such trials, the National Institutes of Health (NIH) were blocked from funding emergency research because such research was deemed to pose more than minimal risk to subjects. 3,4 Minimal risk is a condition precedent for waiving consent under the Common Rule, which applies to all research funded by the federal government other than FDA. 5 In 1996, the FDA promulgated a new, more detailed rule, the exception from informed consent (EFIC).…”

Section: Introductionmentioning

confidence: 99%

“…Federal regulations in the United States have allowed research conducted under the auspices of the Food and Drug Administration (FDA) to be conducted without consent in emergency, lifesaving situations since 1963 1,2 . In the early 1990s, with increasing attention to the need to conduct such trials, the National Institutes of Health (NIH) were blocked from funding emergency research because such research was deemed to pose more than minimal risk to subjects 3,4 . Minimal risk is a condition precedent for waiving consent under the Common Rule, which applies to all research funded by the federal government other than FDA 5 .…”

Section: Introductionmentioning

confidence: 99%

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

Snyder

Academic Emergency Medicine

2023

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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.

mentioning

confidence: 99%

A Census of Clinical Trials Conducted Under the US Exception from Informed Consent Rule

Snyder

2022

Preprint

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Background: The US Food and Drug Administration and National Institutes of Health adopted the Exception from Informed Consent (EFIC) rule in 1996, permitting waiver of informed consent for certain emergency research, including trials funded by the federal government. The rule requires that prospective consent be sought when practicable from patients or their Legally Authorized Representative(s) (LAR), and for those enrolled without consent, the patient or their LAR must be given information and 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 multi-pronged search to try and identify all trials conducted under the EFIC rule, drawing on numerous reviews, Medline and Google searches (including of the clinicaltrials.gov registry), examination of the FDA's docket, posting an inquiry on the IRB 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 105 trials as of April 1, 2022: 77 complete, 10 recruiting, 10 registered on clinicaltrials.gov but not yet recruiting, 5 trials that were abandoned before enrolling any subjects, and 3 trials in early planning. Nine of the 77 completed trials were pilot or feasibility trials. Of 68 completed full trials, 30 (44.1%) were terminated early. The most common reason for early termination was futility or safety (17 trials, 25.0%) followed by poor recruitment (9 trials, 13.2%). The rate of conduct of trials has been remarkably constant since 2001, with roughly 18 trials started in each 5-year period. Conclusions: The rate of early termination of EFIC trials for futility or safety appears higher than for other kinds of clinical research. We provide the list of trials in a Supplement for further in-depth data collection and analysis of this set of trials.