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The nature of the review of local context by institutional review boards (IRBs) is vague. Requirements for single IRB review of multicenter trials create a need to better understand interpretation and implementation of local-context review and how to best implement such reviews centrally. We sought a pragmatic understanding of IRB local-context review by exploring stakeholders\' attitudes and perceptions. Semistructured interviews with 26 IRB members and staff members, institutional officials, and investigators were integrated with 80 surveys of similar stakeholders and analyzed with qualitative theme-based text analysis and descriptive statistical analysis. Stakeholders described what they considered to be local context, the value of local-context review, and key processes used to implement review of local context in general and for emergency research conducted with an exception from informed consent. Concerns and potential advantages of centralized review of local context were expressed. Variability in perspectives suggests that local-context review is not a discrete process, which presents opportunities for defining pathways for single IRB review.

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.
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.
We identified a total of 110 trials as of the end of April 2022: 78 complete, 13 recruiting, seven registered on clinicaltrials.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.
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.

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.

Community consultation (CC) is fundamental to the Exception from Informed Consent (EFIC) process for emergency research, designed to inform and receive feedback from the target study population about potential risks and benefits. To better understand the effectiveness of different techniques for CC, we evaluated EFIC processes at two centers participating in a trial of early cardiac catheterization following out-of-hospital cardiac arrest.
We studied the Institutional Review Board-approved CC activities at Maine Medical Center (MMC) and University of Arizona (AZ) in support of NCT02387398. In Maine, the public was consulted by survey at a professional basketball game and in the emergency department waiting room (in-person group), by multimedia direction to an online website (online group), and by mail (mailing group). Arizona respondents were either approached at a county fair (in-person group) or were directed to an online survey (online group) via social media advertising.
Among 2185 survey respondents, approval rates were high for community involvement and personal participation without individual consent. Community consultation using in-person, online, and mailed surveys offered slightly different approval rates, and the rate of responses by modality differed by age and education level but not ethnicity. Print advertising was the least cost effective at $442 per completed survey.
Canvassing at public events was the most efficient mode of performing CC, with approval rates similar to mailings, online surveys, and canvassing in other locations. Print advertisements in local papers had a low yield and cost more than other approaches.

Urodele amphibians, such as newts, can regenerate a functional limb, including joints, after amputation at any level along the proximal-distal axis of the limb. The blastema can regenerate the limb morphology largely independently of the stump after proximal-distal identity has been established, but the remaining and regenerated tissues must be structurally reintegrated (matched in size and shape). Here we used newt joint regeneration as a model to investigate reintegration, because a functionally interlocking joint requires structural integration between its opposing skeletal elements. After forelimbs were amputated at the elbow joint, the joint was regenerated between the remaining and regenerated skeletal elements. The regenerated cartilage was thick around the amputated joint to make a reciprocally interlocking joint structure with the remaining bone. Furthermore, during regeneration, the extracellular matrix of the remaining tissues was lost, suggesting that the remaining tissues might contribute to the morphogenesis of regenerating cartilage. Our results showed that the area of the regenerated cartilage matched the area of the apposed remaining cartilage, thus contributing to formation of a functional structure.

The purpose of this study was to evaluate the attitudes and opinions of a broad population of EMS providers on enrolling patients in research without consent. A survey was conducted in 2010 of all EMS providers who participated in the National Registry of Emergency Medical Technicians (NREMT) reregistration process, which included half of all registered providers. Each reregistration packet included our optional survey, which had nine 6-point Likert scale questions concerning their opinion of research studies without consent as well as 8 demographic questions. Responses were collapsed to agree and disagree and then analyzed using descriptive statistics with 99% confidence intervals. A total of 65,993 EMS providers received the survey and 23,832 (36%) participated. Most respondents agreed (98.4%, 99%CI: 98.2-98.6) that EMS research is important, but only 30.9% (99%CI: 30.1-31.6) agreed with enrolling patients without their consent when it is important to learn about a new treatment. Only 46.6% (99%Cl: 45.7-47.4) were personally willing to be enrolled in a study without their consent. A majority (68.5% [99%Cl: 67.7-69.3]) of respondents believed that EMS providers should have the individual right to refuse to enroll patients in EMS research. While the majority of respondents agreed that EMS research is important, considerably less agree with enrolling patients without consent and less than half would be willing to be enrolled in a study without their consent. Prior to starting an Exception from Informed Consent (EFIC) study, researchers should discuss with EMS providers their perceptions of enrolling patients without consent and address their concerns.