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Introduction: Emergency clinical research has played an important role in improving outcomes for acutely ill patients. This is due in part to regulatory measures that allow Exception From Informed Consent (EFIC) trials. The Food and Drug Administration (FDA) requires sponsor-investigators to engage in community consultation and public disclosure activities prior to initiating an Exception From Informed Consent trial. Various approaches to community consultation and public disclosure have been described and adapted to local contexts and Institutional Review Board (IRB) interpretations. The COVID-19 pandemic has precluded the ability to engage local communities through direct, in-person public venues, requiring research teams to find alternative ways to inform communities about emergency research. Methods: The PreVent and PreVent 2 studies were two Exception From Informed Consent trials of emergency endotracheal intubation, conducted in one geographic location for the PreVent Study and in two geographic locations for the PreVent 2 Study. During the period of the two studies, there was a substantial shift in the methodological approach spanning across the periods before and after the pandemic from telephone, to in-person, to virtual settings. Results: During the 10 years of implementation of Exception From Informed Consent activities for the two PreVent trials, there was overall favorable public support for the concept of Exception From Informed Consent trials and for the importance of emergency clinical research. Community concerns were few and also did not differ much by method of contact. Attendance was higher with the implementation of virtual technology to reach members of the community, and overall feedback was more positive compared with telephone contacts or in-person events. However, the proportion of survey responses received after completion of the remote, live event was substantially lower, with a greater proportion of respondents having higher education levels. This suggests less active engagement after completion of the synchronous activity and potentially higher selection bias among respondents. Importantly, we found that engagement with local community leaders was a key component to develop appropriate plans to connect with the public. Conclusion: The PreVent experience illustrated operational advantages and disadvantages to community consultation conducted primarily by telephone, in-person events, or online activities. Approaches to enhance community acceptance included partnering with community leaders to optimize the communication strategies and trust building with the involvement of Institutional Review Board representatives during community meetings. Researchers might need to pivot from in-person planning to virtual techniques while maintaining the ability to engage with the public with two-way communication approaches. Due to less active engagement, and potential for selection bias in the responders, further research is needed to address the costs and benefits of virtual community consultation and public disclosure activities compared to in-person events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research. Data sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK). Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data. Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design.

BackgroundFederal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries.MethodsWe conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC.ResultsWe enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months.ConclusionsIn a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.

Aim: To explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC). Methods: We performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items. Analyses included descriptive statistics for quantitative data and thematic analysis for qualitative data. Results: Sixty-seven participants contributed to 60 survey responses (53 individuals and 7 families for whom 2 family members participated). Most participants answered favorably toward the planned trial: 55/58 (95%) reported that the trial seemed “somewhat” or “very important”; 52/57 (91%) felt the use of EFIC was “somewhat” or “completely acceptable”; and 43/58 (74%) said they would be “somewhat” or “very likely” to allow their child to participate. Five themes emerged supporting participation in the planned trial: 1) trust in the clinical team; 2) familiarity with the study intervention (epinephrine); 3) study protocol being similar to standard care; 4) informed consent during an emergency was not feasible; and 5) importance of research. Barriers to potential participation included requests for additional time to decide about participating and misconceptions about study elements, especially eligibility. Conclusions: Families of PICU patients generally supported plans for an emergency interventional trial using EFIC. Future inpatient EFIC studies may benefit from highlighting the themes identified here in their educational materials.

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 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. 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. [ABSTRACT FROM AUTHOR]

Adaptive trials, clinical trial design, exception from informed consent, hemorrhagic shock, medical ethics, platform trials, trauma resuscitation To date, there have been no prospective randomized trauma treatment clinical trials conducted by US military trauma units in combat theaters of operation.39,40 Because there is a high burden of hemorrhage due to traumatic injury in combat, the wounding agents differ from those seen in non-combat environments, and the military population stands to immediately gain from advances in combat trauma care to eliminate potentially preventable death, it is important to consider whether an EFIC platform trial could be conducted in a combat zone. An adaptive platform trial for evaluating treatments in patients with life-threatening hemorrhage from traumatic injuries: Ethical and US regulatory considerations Keywords: adaptive trials; clinical trial design; exception from informed consent; hemorrhagic shock; medical ethics; platform trials; trauma resuscitation EN adaptive trials clinical trial design exception from informed consent hemorrhagic shock medical ethics platform trials trauma resuscitation S255 S265 11 08/01/22 20220802 NES 220802 INTRODUCTION Clinical trial design, with the use of adaptive methods, has evolved in recent years to become more efficient in answering questions and limiting the exposure of subjects to potentially inferior treatment options.1,2 These changes may require new thinking in addressing the ethical and regulatory requirements of conducting clinical trials. [Extracted from the article]

Keywords: adaptive trials; clinical trial design; exception from informed consent; hemorrhagic shock; medical ethics; platform trials; trauma resuscitation EN adaptive trials clinical trial design exception from informed consent hemorrhagic shock medical ethics platform trials trauma resuscitation S231 S241 11 08/01/22 20220802 NES 220802 INTRODUCTION Post-traumatic hemorrhage remains the leading cause of death in people aged one to forty-four in the United States.1 The initial management of the severely injured patient, whether in the prehospital, emergency department, operating room, or critical care setting is inherently complex, with diagnostic and therapeutic strategies occurring both simultaneously and sequentially.2,3 While substantial advancements have been made in determining optimal resuscitation in both civilian and military settings, the nature of trauma with its diverse mechanisms of injury, heterogeneous patient population, and variable access to resources makes it a challenging field in which to perform randomized controlled trials (RCTs). For experimental treatments that enter the platform trial sometime after the start of the trial, the concurrent controls are patients that, at the time of their randomization, could have been assigned to that treatment. An adaptive platform trial for evaluating treatments in patients with life-threatening hemorrhage from traumatic injuries: Rationale and proposal Assessing the multiple therapies used in the treatment of critically injured patients via traditional RCTs would require a sequence of trials, each testing a single or few treatment arms in a restricted population. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with acute ischemic stroke (AIS) and neurologic deficits are often unable to provide consent and excluded from emergency research participation. Experiences with exception from informed consent (EFIC) to facilitate research on potentially life-saving emergency interventions are limited. Here, we describe our multifaceted approach to EFIC approval for an ongoing randomized clinical trial that compares sedation versus general anesthesia (SEGA) approaches for endovascular thrombectomy during AIS. METHODS: We published a university clinical trial website with EFIC information. We initiated a social media campaign on Facebook within a 50 mile radius of Texas Medical Center. Advertisements were linked to our website, and a press release was issued with information about the trial. In-person community consultations were performed, and voluntary survey information was collected. RESULTS: A total of 193 individuals (65% female, age 46.7 ± 16.6 years) participated in seven focus group community consultations. Of the 144 (75%) that completed surveys, 88.7% agreed that they would be willing to have themselves or family enrolled in this trial under EFIC. Facebook advertisements had 134,481 (52% females; 60% ≥45 years old) views followed by 1,630 clicks to learn more. The website had 1130 views (56% regional and 44% national) with an average of 3.85 min spent. Our Institutional Review Board received zero e-mails requesting additional information or to optout. CONCLUSION: Our social media campaign and community consultation methods provide a significant outreach to potential stroke patients. We hope that our experience will inform and help future efforts for trials seeking EFIC.

Background: Exception from informed consent (EFIC) enables the enrollment of research subjects with emergent conditions to clinical trials without prior consent. EFIC study approval requires community consultation and public disclosure. We hypothesized that the integration of social media with targeted emails and in‐person outreach is an effective community consultation strategy. Methods: We utilized social media with targeted emails and in‐person outreach for the community consultation of the ACCESS cardiac arrest trial. Study advertisements were disseminated using Facebook and Instagram, and targeted emails were sent to emergency medicine, prehospital, and cardiology providers. We also interviewed at‐risk individuals with cardiac conditions, their caretakers, and patient advocacy groups. Participants were asked to complete a survey about their opinions about the study. Results: We collected 559 surveys over an 8‐week period, and 70.5% of the surveys were obtained using social media. The median (IQR) age of survey respondents was 44 (33‐57) years; 89.9% were White and 60.1% were women. A total of 91.3% believed ACCESS was an important study. Compared to the in‐person group, more from social media (81.8% vs. 63.3%, p < 0.05) and targeted email (77.4% vs. 63.3%, p < 0.05) groups said they would include their loved ones in the study. More from the in‐person group believed that their opinion would be considered seriously compared to the social media (75.9% vs. 62.6%, p < 0.05) and targeted email (75.9% vs. 54.5%, p < 0.05) groups. The incorporation of social media and targeted emails for community consultation reduced the cost per survey by fourfold compared to an in‐person–only strategy. Conclusions: The integration of social media with targeted emails and in‐person outreach was a feasible and cost‐saving approach for EFIC community consultation. Future work is necessary to determine the perception and best utilization of social media for community consultation. [ABSTRACT FROM AUTHOR]

Abstract Objectives With increased focus on early resuscitation methods following injury to improve patient outcomes, studies are employing exception from informed consent (EFIC) enrollment. Few studies have assessed patients’ opinions following participation in an EFIC study, and none have been conducted within the realm of traumatic hemorrhage. We surveyed those patients and surrogates previously enrolled in the Prehospital Air Medical Plasma (PAMPer) Trial to clarify their opinions related to consent and emergency research. Methods Telephone calls were made between January–June 2019 to all patients who were enrolled under EFIC in the PAMPer study at the Pittsburgh site (169 of the 501 total patients enrolled, May 2014-Oct 2017) and their surrogates. Questions gauging approval of EFIC enrollment were asked before discussion of PAMPer trial outcomes, after disclosure of positive outcomes, and after a hypothetical negative trial outcome was proposed. Results Of the total 647 telephone calls made, ninety-three interviews, reflecting 70 of 169 patient enrollments, were conducted. This included 13 in which only the patient was interviewed, 23 in which the patient and a surrogate were interviewed, and 34 in which only a surrogate was interviewed. Nearly half (48.4%) of respondents did not recall their personal or family member enrollment in the study. No patients or surrogates recalled hearing about the study through community consultation or being aware of opt out procedures. Patients and surrogates were glad they were enrolled (90.3%), agreed with EFIC use for their personal enrollment (88.17%), and agreed with the general use of EFIC for the PAMPer study (81.7%). Disclosure of the true positive PAMPer study outcome resulted in a significant increase in opinions regarding personal enrollment, EFIC for personal enrollment, and EFIC for general enrollment (all p

In the context of emergency research, researchers can ask the institutional review board (IRB) to waive the regulatory requirement that individuals provide informed consent when enrolling in research studies. A requirement of the waiver of informed consent is that the reviewing IRB must review and approve a community consultation and public disclosure plan. It is critical that an IRB serving as the single IRB (sIRB) for multisite research be thoroughly versed in the local context concerns for each participating site to determine whether the site's community is being adequately consulted about the research in which individuals will be enrolled under an exception to the informed consent requirement. We designed an sIRB review model for evaluating site‐specific community consultation plans that included a local evaluation and feedback step, and we piloted the model with a four‐site, pediatric exception from informed consent (EFIC) clinical trial. We identified three key roles for the model: the sIRB, the investigators, and the representative of the institution's human research protection program (HRPP). We successfully collected the information and local input needed to evaluate each site's community consultation plan and applied the information to a thorough IRB review, despite the geographic distance between the study site and the sIRB. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with acute ischemic stroke (AIS) and neurologic deficits are often unable to provide consent and excluded from emergency research participation. Experiences with exception from informed consent (EFIC) to facilitate research on potentially life-saving emergency interventions are limited. Here, we describe our multifaceted approach to EFIC approval for an ongoing randomized clinical trial that compares sedation versus general anesthesia (SEGA) approaches for endovascular thrombectomy during AIS. METHODS: We published a university clinical trial website with EFIC information. We initiated a social media campaign on Facebook within a 50 mile radius of Texas Medical Center. Advertisements were linked to our website, and a press release was issued with information about the trial. In-person community consultations were performed, and voluntary survey information was collected. RESULTS: A total of 193 individuals (65% female, age 46.7 ± 16.6 years) participated in seven focus group community consultations. Of the 144 (75%) that completed surveys, 88.7% agreed that they would be willing to have themselves or family enrolled in this trial under EFIC. Facebook advertisements had 134,481 (52% females; 60% ≥45 years old) views followed by 1,630 clicks to learn more. The website had 1130 views (56% regional and 44% national) with an average of 3.85 min spent. Our Institutional Review Board received zero e-mails requesting additional information or to optout. CONCLUSION: Our social media campaign and community consultation methods provide a significant outreach to potential stroke patients. We hope that our experience will inform and help future efforts for trials seeking EFIC. [ABSTRACT FROM AUTHOR]

BackgroundThe US federal regulation "Exception from Informed Consent for Emergency Research," 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards determine the adequacy of these activities at a local level. Thus, there is potential for broad interpretation and practice variation.AimTo describe the variation of community consultation and public disclosure activities approved by Institutional Review Boards, and the effectiveness of this process for a multi-center, Exception from Informed Consent, pediatric status epilepticus clinical research trial.MethodsCommunity consultation and public disclosure activities were analyzed for each of the 15 participating sites. Surveys were conducted with participants enrolled in the status epilepticus trial to assess the effectiveness of public disclosure dissemination prior to study enrollment.ResultsEvery Institutional Review Board, among the 15 participating sites, had a varied interpretation of Exception from Informed Consent regulations for community consultation and public disclosure activities. Institutional Review Boards required various combinations of focus groups, interviews, surveys, and meetings for community consultation, and news releases, mailings, and public service announcements for public disclosure. At least 4335 patients received information about the study from these efforts. In all, 158 chose to be included in the "Opt Out" list. Of the 304 participants who were enrolled under Exception from Informed Consent, 12 (5%) had heard about the study through community consultation or public disclosure activities. The activities reaching the highest number of participants were surveys and focus groups associated with existing meetings. Public disclosure activities were more efficient and cost-effective if they were part of an in-hospital resource for patients and families.ConclusionThere is substantial variation in Institutional Review Boards' interpretations of the federal regulations for community consultation and public disclosure. One of the goals of community consultation and public disclosure efforts for emergency research is to provide community members an opportunity to opt out of Exception from Informed Consent research; however, rarely do patients or their legally authorized representatives report having learned about a study prior to enrollment.

Many of the current accepted treatment practices provided to patients in the first critical hour after a traumatic injury, stroke, or cardiac arrest have not been rigorously tested in clinical research trials. The inability to obtain informed consent is often a barrier to research in emergency, time-sensitive situations in which the patient is not able to provide informed consent nor is their family member immediately available to provide consent on behalf of the patient. Planned emergency research, often with exception from informed consent, is a type of research study that involves a patient with a life-threatening medical condition that requires urgent interventions, wherein the current treatments may be unproven or suboptimal, and who, because of their current condition, is unable to provide informed consent. This article summarizes the necessary components for using exception from informed consent in planned emergency research. Understanding the research design, particularly research processes specific to time-critical emergency situations, will ensure that the care provided by stretcher-side emergency nurses will result in optimal patient outcomes and is an integral aspect of emergency nursing practice. [ABSTRACT FROM AUTHOR]

Exception from Informed Consent (EFIC) regulations detail specific circumstances in which Institutional Review Boards (IRB) can approve studies where obtaining informed consent is not possible prior to subject enrollment. To better understand how IRB members evaluate community consultation (CC) and public disclosure (PD) processes and results, semi-structured interviews of EFIC-experienced IRB members were conducted and analyzed using thematic analysis. Interviews with 11 IRB members revealed similar approaches to reviewing EFIC studies. Most use summaries of CC activities to determine community members' attitudes; none reported using specific criteria nor recalled any CC reviews that resulted in modifications to or denials of EFIC studies. Most interviewees thought metrics based on Community VOICES's domains (feasibility, participant selection, quality of communication, community perceptions, investigator/IRB perceptions) would be helpful. IRB members had similar experiences and concerns about reviewing EFIC studies. Development of metrics to assess CC processes may be useful to IRBs reviewing EFIC studies. [ABSTRACT FROM AUTHOR]

We examine the evolution of policies permitting exceptions to or waivers of informed consent for research in the United States. This review reveals that (1) exceptions to the duty to secure informed consent were originally quite narrow; (2) there were two alternative approaches to allowing research on human subjects without their prospective consent: (i) exceptions in which individual capacity to consent is to be assessed and consent tailored to each person's abilities and (ii) waivers of the general requirement for a population of potential subjects, where securing prospective consent would "destroy or invalidate" critically important research; (3) waivers only appeared in the final rulemakings for research regulations issued by the National Institute of Education in 1974 and the Department of Health and Human Services in 1981, limiting the opportunity for the public to weigh in on the scope and use of waivers; and (4) rules adopted since 1981 have almost uniformly added extra requirements to justify waivers. Examples drawn from recent research show expansion of the use of waivers far beyond the bounds originally envisioned. Greater transparency about the use of waivers is needed for the public to weigh in on the standards for foregoing informed consent in human research. [ABSTRACT FROM AUTHOR]

Introduction: In the last several decades, South Korea has rapidly adopted Western customs and practices. Yet, cultural differences between South Korea and the United States exist. The purpose ofthis study was to identify and characterize potential cultural differences in the Korean and US institutional review board (IRB) approach to certain topics.Methods: A qualitative analysis of a 9-item survey, describing 4 research study case scenarios, sent to IRB members from the United States and South Korea. The case scenarios involved the followingissues: (1) the need for consent for retrospective chart review when research subjects receive their care after the study is conceived; (2) child assent; (3) individual versus population benefit; and (4) exception from informed consent in emergency resuscitation research. The free-text responses were analyzed and abstracted for recurrent themes.Results: Twenty-three of the 45 survey recipients completed the survey, for an overall response rate of 51%. The themes that emerged were as follows: (1) the importance of parental authority among Korean participants versus the importance of child autonomy and child assent among US participants; (2) the recognition of the rights of a proxy or surrogate who can represent an individual’s values by all participants; and (3) the importance of the community, expressed by the Korean respondents, versus individualism, expressed by US respondents.Conclusion: Whereas US participants appear to emphasize the importance of the individual and the autonomy of a child, the Korean respondents stressed the importance of parental authority andbenefiting the community, above and beyond that of the individual person. However, there was substantial overlap in the themes expressed by respondents from both countries. [West J Emerg Med.2012;13(4):335–341.]

Find consent processes that protect and preserve patients' autonomy to the extent possible, while also allowing medical progress to occur and giving participants access to potentially beneficial therapies. Doing so may require  a more creative process than just following the rules. [ABSTRACT FROM AUTHOR]

Objectives: With increased focus on early resuscitation methods following injury to improve patient outcomes, studies are employing exception from informed consent (EFIC) enrollment. Few studies have assessed patients' opinions following participation in an EFIC study, and none have been conducted within the realm of traumatic hemorrhage. We surveyed those patients and surrogates previously enrolled in the Prehospital Air Medical Plasma (PAMPer) Trial to clarify their opinions related to consent and emergency research.Methods: Telephone calls were made between January-June 2019 to all patients who were enrolled under EFIC in the PAMPer study at the Pittsburgh site (169 of the 501 total patients enrolled, May 2014-Oct 2017) and their surrogates. Questions gauging approval of EFIC enrollment were asked before discussion of PAMPer trial outcomes, after disclosure of positive outcomes, and after a hypothetical negative trial outcome was proposed.Results: Of the total 647 telephone calls made, ninety-three interviews, reflecting 70 of 169 patient enrollments, were conducted. This included 13 in which only the patient was interviewed, 23 in which the patient and a surrogate were interviewed, and 34 in which only a surrogate was interviewed. Nearly half (48.4%) of respondents did not recall their personal or family member enrollment in the study. No patients or surrogates recalled hearing about the study through community consultation or being aware of opt out procedures. Patients and surrogates were glad they were enrolled (90.3%), agreed with EFIC use for their personal enrollment (88.17%), and agreed with the general use of EFIC for the PAMPer study (81.7%). Disclosure of the true positive PAMPer study outcome resulted in a significant increase in opinions regarding personal enrollment, EFIC for personal enrollment, and EFIC for general enrollment (all p < 0.001). Disclosure of a hypothetical neutral or negative study outcome resulted in significant decreases in opinions regarding EFIC for personal enrollment (p = 0.003) and EFIC for general enrollment (p < 0.001).Conclusions: Clinical trial participants with traumatic hemorrhagic shock enrolled with EFIC, and surrogates of such participants, are generally accepting of EFIC. The results of the trial in which EFIC was utilized significantly affected patient and surrogate agreement with personal and general EFIC enrollment. [ABSTRACT FROM AUTHOR]

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research., Data Sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK)., Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data., Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Abstract Background Exception from informed consent (EFIC) allows clinician scientists to perform much needed emergency research. Obtaining this exception, however, requires many meetings with community groups for consultation, which can make the process time-consuming and expensive. We aim to determine the impact of using social media in lieu of some community meetings in an effort to obtain an EFIC. Materials and methods An economic analysis of four randomized clinical trials was performed. Costs were conservatively estimated using personnel costs, social media costs, and adjusted to 2016 US dollars. People were considered reached if they attended a community meeting or were directed to the study website by social media and spent ≥1 min. Results The Early Whole Blood study required 14 meetings, reached 272 people, and cost $8260 ($30/person reached). The Pragmatic, Randomized Optimal Platelet and Plasma Ratios study required 14 meetings, reached 260 people, and cost $7479 overall ($29/person reached). The Prehospital Tranexamic Acid Use for Traumatic Brain Injury study required 12 meetings, reached 198 people, and cost $6340 ($32/person reached). Only the damage control laparotomy trial utilized social media in lieu of some community meetings. The damage control laparotomy trial required six meetings at which 137 people were reached. The $1000 social media campaign reached 229 people. The cost was $3977 overall and $11/person reached. Conclusions Including a social media campaign during the EFIC process increased the number of potential patients reached and reduced total and per person costs reached costs. Obtaining an EFIC for future emergency clinical trials may be facilitated by the inclusion of a social media campaign. [ABSTRACT FROM AUTHOR]

Background: Exception from infor med consent (EFIC) is allowed using federal regulations 21 CFR 50.24 and facilitates research on patients with critical conditions such as cardiac arrest. Little is known regarding the differences in the application of EFIC requirements such as community consultation (CC), public disclosure (PD) and patient notification. We sought to characterize variations in the fulfillment of EFIC requirements in a national multicenter clinical trial in the United States.Methods: We determined the strategies for fulfillment of EFIC requirements at five regional coordinating centers of the Pragmatic Airway Resuscitation Trial (PART), a cluster-crossover randomized trial comparing airway devices in out-of-hospital cardiac arrest. We collected information from the including site demographics, how CC and PD were implemented, methods undertaken by the site investigative team to meet the local IRB's interpretation, and patient notification timing (post-enrollment). We analyzed the data using descriptive statistics.Results: Sites had multiple approaches to CC, including social media advertising, random digit dialing surveys, working with city officials, and websites with embedded surveys. All sites used more than one approach for conducting CC. Public Disclosure activities included press releases through various means, website documentation, and letters to community members and local officials. Time from CC to study approval ranged from 42 days to 253 days.Conclusion: EFIC implementation varies across sites and highlight community and regional variation. Different EFIC approaches may be needed to effectively accomplish the goals of community consultation, public disclosure, and patient notification. [ABSTRACT FROM AUTHOR]

Aim: U.S. federal regulations for research involving exception from informed consent (EFIC) include stipulations for community consultation (CC) and public disclosure (PD) (FDA 21 CFR 50.24). Published descriptions of PD campaigns include letters to community leaders, media outreach, paid advertising, and community meetings. Whether or not these activities provide measurable impact is unknown, as few prior works have evaluated PD activities with probabilistic polling. The aim of this study is to use polling to assess how much public awareness PD efforts generate.Methods: A 3-month PD campaign similar in scope and scale to PD campaigns described in several recent publications was implemented across a large urban county (pop. 2.55 million). PD included a study website (www.evktrial.org), letters to 300 community leaders/organizations, bilingual media outreach and also phased roll-outs, weeks apart, of newspaper advertisements, mass e-mail messaging, and paid advertising in Facebook® and Twitter® augmented by volunteer social media outreach. During PD we used repeated zip code-targeted online polling via Google Consumer Surveys® to assess community awareness of the proposed EFIC study.Results: Over 3-months all-source exposures to >1 million individuals were estimated, generating ∼5,000 website visits (12-month cumulative, ∼9000). However, general community awareness evaluated through repeated county-wide polling never rose above baseline measurements. CC/PD campaign costs were estimated at $60,000 (USD).Conclusion: A PD campaign in scope and scale common for EFIC studies may not provide measurable impact in a community. Investigators, review boards and regulators could consider these findings when re-examining and/or creating policies for PD for EFIC studies. [ABSTRACT FROM AUTHOR]

Background: Exception from informed consent imposes community consultation and public disclosure requirements on clinical investigation in critically ill and injured patients. In 2011, the Food and Drug Administration instructed sponsors to submit publically disclosed information to the Food and Drug Administration Docket, but to date there has been no comprehensive analysis of available data. We summarized the community consultation and public disclosure practices of exception from informed consent trials published on the Food and Drug Administration Docket in order to better understand the breadth of common practices that exists among acute care clinical research. Methods: We performed quantitative and qualitative analysis of Docket FDA-1995-S-0036 from its initiation until June 2017 in order to summarize existing practices. We developed a 4-point scoring system to categorize public disclosure and community consultation based on inclusion of key components such as a detailed plan, schedule of events conducted, results, and materials uploaded. Results: The 177 docket submissions represented 34 trials. Material related to public disclosure accounted for 49% of pages, community consultation 45%, and 6% other. The median Docket Review Content Score for public disclosure was 3 (mean: 2.5, range: 0–4) and 2 (mean: 2.1, range: 0–4) for community consultation materials. Conclusion: The public information contained in the Docket varies broadly by trial and content. Additionally, as evidenced by the wide range of the Docket Review Content Score, submission guidelines are not followed uniformly. Given the apparent uncertainty about what should be submitted, and the need for best practice recommendations, it is valuable to categorize and summarize existing community consultation and public disclosure content. [ABSTRACT FROM AUTHOR]

Introduction: In the last several decades, South Korea has rapidly adopted Western customs and practices. Yet, cultural differences between South Korea and the United States exist. The purpose ofthis study was to identify and characterize potential cultural differences in the Korean and US institutional review board (IRB) approach to certain topics.Methods: A qualitative analysis of a 9-item survey, describing 4 research study case scenarios, sent to IRB members from the United States and South Korea. The case scenarios involved the followingissues: (1) the need for consent for retrospective chart review when research subjects receive their care after the study is conceived; (2) child assent; (3) individual versus population benefit; and (4) exception from informed consent in emergency resuscitation research. The free-text responses were analyzed and abstracted for recurrent themes.Results: Twenty-three of the 45 survey recipients completed the survey, for an overall response rate of 51%. The themes that emerged were as follows: (1) the importance of parental authority among Korean participants versus the importance of child autonomy and child assent among US participants; (2) the recognition of the rights of a proxy or surrogate who can represent an individual’s values by all participants; and (3) the importance of the community, expressed by the Korean respondents, versus individualism, expressed by US respondents.Conclusion: Whereas US participants appear to emphasize the importance of the individual and the autonomy of a child, the Korean respondents stressed the importance of parental authority andbenefiting the community, above and beyond that of the individual person. However, there was substantial overlap in the themes expressed by respondents from both countries.

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. [ABSTRACT FROM PUBLISHER]

Aim: To explore perspectives of families in the pediatric intensive care unit (PICU) about an emergency interventional trial on peri-arrest bolus epinephrine for acute hypotension using Exception From Informed Consent (EFIC)., Methods: We performed face-to-face interviews with families whose children were hospitalized in the PICU. A research team member provided an educational presentation about the planned trial and administered a survey with open- and closed-ended items. Analyses included descriptive statistics for quantitative data and thematic analysis for qualitative data., Results: Sixty-seven participants contributed to 60 survey responses (53 individuals and 7 families for whom 2 family members participated). Most participants answered favorably toward the planned trial: 55/58 (95%) reported that the trial seemed "somewhat" or "very important"; 52/57 (91%) felt the use of EFIC was "somewhat" or "completely acceptable"; and 43/58 (74%) said they would be "somewhat" or "very likely" to allow their child to participate. Five themes emerged supporting participation in the planned trial: 1) trust in the clinical team; 2) familiarity with the study intervention (epinephrine); 3) study protocol being similar to standard care; 4) informed consent during an emergency was not feasible; and 5) importance of research. Barriers to potential participation included requests for additional time to decide about participating and misconceptions about study elements, especially eligibility., Conclusions: Families of PICU patients generally supported plans for an emergency interventional trial using EFIC. Future inpatient EFIC studies may benefit from highlighting the themes identified here in their educational materials., (© 2023 The Authors.)

Objectives. The purpose of this study was to evaluate community member feedback from community consultation and public disclosure activities performed for a clinical investigation involving a device designed to treat traumatic brain injury in prehospital contexts. The clinical investigation of that device was to be performed under the federal regulations providing an exception from prospective informed consent requirements in emergency settings. Secondarily, we sought to assess the community consultation process by measuring the levels of outreach provided by the different communication methods used in these activities, with special attention to the effectiveness of social media for community outreach. Methods and setting. The medical device investigation consists of a single-site pilot study based at a 345-bed community hospital in east central Illinois, which also serves as the area's only level I trauma center. Investigators, in collaboration with the local institutional review board, fulfilled community consultation and public disclosure requirements through four public town hall meetings, seven targeted focus groups, targeted mailings to 884 community leaders and researchers, a press conference and press release, internal and external websites, and multiple postings to the hospital's Facebook and Twitter accounts. Community members provided feedback by completing paper or electronic comment cards. Results. A total of 428 community members attended the four town hall meetings and seven focus group sessions. Attendance at each meeting ranged from 4 to 20 attendees for the town hall meetings and 8 to 140 attendees for the focus groups. The investigation's external website received 626 unique visitors and the intranet website received 528 unique visits. Social media postings on Facebook and Twitter received six comments and eight 'likes' to indicate that an individual read the posting. In total, attendees completed 175 comment cards to provide their feedback. Community member attitudes regarding the research were very positive, with 173 (98.8%) comment card respondents viewing the research as beneficial and 162 (92.6%) indicating that they would allow themselves or their family members to participate in the research. Conclusions. The internal and external websites provided the most effective means for sharing research-related information to community members. While cost-effective, social media outreach was very limited and did not foster communication with community members. [ABSTRACT FROM AUTHOR]

Abstract: Background: We sought to characterize persons who requested to opt out of an exception from informed consent (EFIC) cardiac arrest trial and their reasons for opting out. Methods: At one site of a multi-site, out-of-hospital, cardiac arrest EFIC trial (September 2007 – June 2009), persons who did not want to participate in the study could request an opt-out “NO STUDY” bracelet to prevent trial enrollment. We surveyed all persons who requested a bracelet by phone interview, web or mail. Opt-out bracelets were advertised in all public communication about the study, including community consultation and public disclosure efforts. Survey questions included demographics, Likert scale items about attitudes toward the trial and research in general, plus open-ended questions. We used descriptive statistics for standardized questions and qualitative analysis to identify common themes from open-ended questions. Results: Sixty bracelets were requested by 50 individuals. Surveys were completed by 46 persons (92% response rate). Seventy percent of respondents agreed emergency research is important, but 87% objected to any research without consent. In the qualitative analysis, 5 overlapping themes emerged: questioning the ethics of EFIC research; concerns about how the study would impact end-of-life preferences; subjective emotions including sarcasm, anger, and allusions to past unethical research; negative reference to unrelated public health controversies; and objections to the study protocol based on misinformation. Conclusions: A primary reason for opting out from this EFIC trial was opposition to all research without informed consent, despite stated support for emergency research. Understanding the demographics and beliefs of persons opting out may aid researchers planning EFIC studies and help provide clarity in future EFIC-related community education efforts. [Copyright &y& Elsevier]

Summary: Objective: To evaluate the feasibility of a prehospital randomized controlled trial comparing transcutaneous pacing (TCP) with dopamine for unstable bradycardia. Methods: Unstable bradycardic patients who failed to respond to a fluid bolus and up to 3mg atropine were enrolled. The intervention was dopamine or TCP with crossover to dopamine if TCP failed. The primary outcome was survival to discharge or 30 days. Randomization compliance, safety, follow-up rates, primary outcome, and sample size requirements were assessed. Results: Of 383 patients with unstable bradycardia, 151 (39%) failed to respond to atropine or fluid and were eligible for enrolment and 82 (55%) were correctly enrolled. Fifty-five (36%) of eligible patients could not be enrolled for practical reasons; 3 had advance directives, 32 met inclusion criteria on arrival at hospital and in 20 cases, paramedics chose not to enroll based on the circumstances of the case. The remaining 13 were missed cases; 8 were missing randomization envelopes and in 5, the paramedic forgot. Randomization compliance was 95% (78/82). Forty-two (51%) patients were randomized to TCP and seven of these crossed over to dopamine. Two cases were randomized but did not receive the intervention; either due to lack of time or loss of IV access. Three adverse events occurred in each group. Survival to discharge or 30 days in hospital was 70% (28/40) and 69% (29/42) in the dopamine and TCP groups, respectively with 100% follow up. To detect a 10% relative difference in 30 days survival between treatment arms, a sample size of 690 per group would be required. Conclusions: It is feasible to conduct a prehospital randomized controlled trial of TCP for unstable bradycardia and a definitive trial would require a multi-centre study. [Copyright &y& Elsevier]

Objectives: The Food and Drug Administration (FDA) requires researchers to consult with the community prior to conducting research with exception from informed consent, but little is known about whether people support this and, if they do, who researchers should consult. We sought to determine if people could identify communities and leaders of those communities who researchers should consult with to represent their views about research that requires an exception from informed consent. Methods: We conducted a cross-sectional interview study using a convenience sample of patients seeking care in an urban emergency department (ED) to determine if people belonged to specific communities and, if they did, if they could identify communities and leaders appropriate for consultation. Descriptive statistics were used to represent our findings. Results: Most of the 262 participants approached for the study completed the interview (199; 76%). Of those interviewed, 122 (61%) were African American, 54 (27%) were white, 83 (42%) were male, and the mean (±standard deviation [SD]) age was 36.2 ± 14.4 years. Most, (194; 97%), identified that they belonged to a community and most (177; 89%), said that researchers could consult at least one of their communities for consultation about an exception from informed consent study. Participants typically named geographic and religious-affiliated communities and leaders as appropriate for consultation. Conclusion: Most participants identified a community and a leader of that community who researchers could consult about research with exception from informed consent. Geographic and faith-based organizations could play an important role in consultation. [ABSTRACT FROM AUTHOR]