Enrollment in research under exception from informed consent: The Patients’ Experiences in Emergency Research (PEER) study

doi:10.1016/j.resuscitation.2013.04.006

Resuscitation

Volume 84, Issue 10, October 2013, Pages 1416-1421

https://doi.org/10.1016/j.resuscitation.2013.04.006 Get rights and content

Abstract

Background

Resuscitation research requires an exception from informed consent (EFIC). Despite concerns that patients may find EFIC unacceptable, the views and experiences of patients enrolled in an EFIC study are largely unknown.

Methods

The Patients’ Experience in Emergency Research (PEER) study was nested within the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) for pre-hospital treatment of status epilepticus. PEER included 61 EFIC enrollees or their surrogates from 5 sites. Interviews used a structured, interactive guide focusing on acceptance of EFIC enrollment in RAMPART and existing regulatory protections. Simple statistics were generated, and textual data were analyzed for common themes.

Results

24 enrolled patients and 37 surrogates were successfully interviewed. 49/60 (82%) were glad they or their family member were included in RAMPART; 54/57 (95%) felt research on emergency seizure treatment is important. 43/59 (73%) found their inclusion under EFIC acceptable; 10 (17%) found it unacceptable, and 6 (10%) were neutral. There were no statistically significant interactions between enrollment attitudes and demographic characteristics, though there were trends toward lower acceptance among interviewees who were non-white, less educated, or had prior research experience. The most common concerns related to lack of consent prior to RAMPART enrollment. Positive responses related to perceived medical benefits, recognition of the impracticality of consent, and wanting doctors to do what needs to be done in emergencies. Many participants had difficulty understanding the trial and EFIC.

Conclusions

Most subjects had positive views of enrollment, and acceptance generally correlated with results of community consultation studies.

Introduction

Federal regulations allowing an exception from informed consent (EFIC) for research in emergency settings have facilitated pivotal trials, but EFIC research remains challenging and controversial.1, 2 Some challenges stem from requirements for community consultation and public disclosure, but fundamental concerns remain about attitudes of the public and enrolled patients. Patients’ attitudes are particularly relevant, because EFIC regulations are designed to facilitate research in settings where consent is not possible but not to take advantage of incapacity in order to enroll patients against their wishes.³

There is a body of literature addressing attitudes toward EFIC, mostly in the context of community consultation efforts and surveys of the general public.⁴ Approval of the concept of EFIC ranges widely (from 36% to 81%).5, 6, 7, 8, 9 Acceptance of hypothetical personal EFIC enrollment scenarios has also varied significantly (from 45% to 94%).7, 10, 11 In contrast, several studies involving patients who have survived conditions such as stroke, traumatic brain injury, and cardiac arrest have reported greater support.12, 13 A recent Finnish study similarly found broad EFIC support among individuals, physicians, and surrogates involved in a pre-hospital trial of hypothermia induction after cardiac arrest.¹⁴ However, these patients had been enrolled in the hypothermia trial under surrogate consent rather than under EFIC.

While informative, these studies have thus reported hypothetical views on EFIC enrollment. Moreover, most have utilized closed-ended survey instruments offering little insight into reasons for particular views or attitudes. It is unknown whether these data reflect views of patients (or surrogates) actually enrolled in an EFIC trial. The Patients’ Experiences in Emergency Research (PEER) study was nested within the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) by Silbergleit et al. and was designed to address these knowledge gaps.¹⁵

Section snippets

Methods

The principal objective was to assess the views of actual EFIC subjects and surrogates regarding acceptability of EFIC enrollment. Other goals were to assess patient and study factors predicting acceptance of EFIC enrollment and to evaluate the accuracy of community consultation in predicting enrollees’ concerns. PEER was nested within RAMPART, a double-blind, randomized, noninferiority trial comparing intravenous lorazepam with intramuscular midazolam in pre-hospital treatment of status

Study population

In total, 62 interviews were conducted. One could not be analyzed due to a recording failure. Two were terminated prematurely for reasons unrelated to interview content, though available data were included. The sample size for most questions is thus 59. The denominator for each question reflects the number of individuals asked that question.

Total RAMPART enrollment at PEER sites was 245; however, accurate contact information was not available for many subjects, and some sites were able to

Discussion

This is the first study to interview individuals and surrogates included in an EFIC study and employed a design allowing insight into respondents’ understanding and reasoning. In these respects, these data are novel and begin to fill an important knowledge gap.

One goal of this study was to assess whether acceptance of EFIC enrollment is similar among EFIC enrollees and participants in community consultation efforts required by U.S. EFIC regulations. The rate of EFIC acceptance almost exactly

Conclusion

This study is the first to report attitudes of actual EFIC enrollees and surrogates. Interviewees were generally accepting of enrollment and, while sometimes concerned about lack of consent, generally accepting of EFIC. Our findings suggest community consultation efforts do not systematically over-represent acceptance among enrollees; however, we caution against over-interpretation of community consultation acceptance rates given prevalent misunderstanding of study content. Important topics for

Conflict of interest statement

Funding for the PEER study and the RAMPART study were received from NINDS as disclosed in the manuscript. The authors report no other significant financial conflicts of interest relevant to this study.

Acknowledgments

The PEER study (1R03NS066378-01) and the RAMPART study (U01NS056975 and U01NS059041) were funded by the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NINDS played no role in the design of the study, interpretation of data, or development of the manuscript.

References (22)

M.H. Biros et al.
Community attitudes towards emergency research and exception from informed consent
Resuscitation
(2009)
N. Dickert et al.
Patients’ perceptions of research in emergency settings: a study of survivors of sudden cardiac death
Soc Sci Med
(2009)
A. Kämäräinen et al.
Conduct of emergency research in patients unable to give consent—experiences and perceptions of patients, their consent providing next of kin, and treating physicians following a prehospital resuscitation trial
Resuscitation
(2012)
L. Cearnal
The birth of the NETT: NIH-funded network will launch emergency neurological trials
Ann Emerg Med
(2006)
C. Snowdon et al.
Making sense of randomization; responses of parents of critically ill babies to random allocation of treatment in a clinical trial
Soc Sci Med
(1997)
U.S. Food and Drug Administration. Title 21 (Code of Federal Regulations), Part 50.24 Protection of Human Subjects...
U.S. Department of Health and Human Services and Food and Drug Administration. Guidance for Institutional Review...
E.A. Largent et al.
Is emergency research without initial consent justified? The consent substitute model
Arch Intern Med
(2010)
J.M. Baren et al.
The research on community consultation: an annotated bibliography
Acad Emerg Med
(2007)
L.D. Richardson et al.
Research without consent: community perspectives from the Community VOICES Study
Acad Emerg Med
(2005)

W. Triner et al.

Exception from informed consent enrollment in emergency medical research: attitudes and awareness

Acad Emerg Med

(2007)

Cited by (38)

What have we learned from the RAMPART and ESETT randomized controlled trials?
2023, Epilepsy and Behavior
Lessons learned from the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) and Established Status Epilepticus Treatment Trial (ESETT) trials are considered in three ways. First, by asking about the questions the trials were primarily designed to answer, then about the context of the intervention and characteristics of the patients described in secondary analyses, and finally, about what was learned about how to conduct trials in this space. The talk concludes with suggestions and a vision for how to best conduct future trials investigating status epilepticus. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.
Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers
2023, Resuscitation Plus
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).
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.
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.
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.
Patient and Surrogate Postenrollment Perspectives on Research Using the Exception From Informed Consent: An Integrated Survey
2020, Annals of Emergency Medicine
Citation Excerpt :
There are multiple reports of individuals’ attitudes toward exception from informed consent studies in the context of pretrial community consultation.7-9 What data do exist on attitudes of enrolled patients and surrogates have suggested that they are generally positive and similar to those of community consultation reports.10,11 However, these studies included a small proportion of trial participants and could have been subject to selection bias.
It is important for researchers interested in trials using the exception from informed consent to understand the views and experiences of enrolled individuals. Previous studies have shown that patient and surrogate attitudes are generally positive. These studies were small and did not include pediatric patients, and interviews were often conducted long after trial enrollment. This study sought to explore attitudes toward exception from informed consent in a larger sample and more contemporaneous setting.
A 10-item paper-and-pencil survey was integrated into the Established Status Epilepticus Treatment Trial, a randomized trial of 3 treatments for benzodiazepine-refractory status epilepticus in pediatric and adult patients. Primary domains included attitudes toward trial enrollment, exception from informed consent, and community consultation. Simple descriptive statistics, χ², and Fisher’s exact tests were conducted.
Of 317 patients and surrogates, 90% agreed with or were neutral about the statement “I am glad that I/my family member was included in the Established Status Epilepticus Treatment Trial research study,” whereas 10% disagreed. Twenty-seven percent disagreed with enrollment in the study without prospective consent. Black participants were more likely than white, other race, and unknown-race participants to disagree with enrollment without prospective consent (36% versus 23%, 14%, and 14%, respectively). Participants indicated that patients (81%), their families (65%), and those at risk for seizures (51%) were most important to include in community consultation.
This study aimed to explore attitudes toward exception from informed consent enrollment among participants at all sites in a large, multicenter exception from informed consent trial. General acceptance of trial enrollment was high; acceptance of exception from informed consent specifically was somewhat lower, especially among black participants. Our findings provide further support for targeted community consultation focusing on individuals with connections to the disease under study. Future research should focus on communication in the postenrollment period, especially with individuals who may have concerns about exception from informed consent.
Variations in the application of exception from informed consent in a multicenter clinical trial
2019, Resuscitation
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.
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.
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.
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.
Approaches to community consultation in exception from informed consent: Analysis of scope, efficiency, and cost at two centers
2018, Resuscitation
Citation Excerpt :
This would have made random-digit-dialing four times as expensive per survey as any other approach. Surveys, both online and in person, have been included in many EFIC trials, and compare favorably to community meetings and random-digit-dialing [6–11,14–21]. Survey data exist in the literature for comparison, its costs are substantially lower, and the public is more likely to participate since it takes less time than a community meeting [14] and is less personally disruptive than random digit dialing.
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.
Research in the emergency care environment
2017, Clinical and Translational Science: Principles of Human Research: Second Edition
The United States spends two trillion dollars annually on health care with as much as 15–20% being spent in acute care and emergency situations. Research is needed to inform evidence-based, efficient, and cost-effective patient care. Clear evidence is lacking for many treatments, especially in emergency care environment where research is logistically difficult. This chapter reviews the specific issues involved in implementing clinical trials and other research in emergency care environments. The chapter will also provide strategies for successful implementation, including strategies to improve recruitment and retention. Specifically, the chapter will deal with trial design, identification of subjects, development of multidisciplinary research teams, inclusion of prehospital agencies, informed consent process (including rationale and methods to implement exception from informed consent, protocols), and strategies to optimize subject and provider compliance as well as methods to improve subject follow-up.

View all citing articles on Scopus

^☆: A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.04.006.

View full text

Clinical paperEnrollment in research under exception from informed consent: The Patients’ Experiences in Emergency Research (PEER) study☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Study population

Discussion

Conclusion

Conflict of interest statement

Acknowledgments

Resuscitation

Soc Sci Med

Resuscitation

Ann Emerg Med

Soc Sci Med

Is emergency research without initial consent justified? The consent substitute model

Arch Intern Med

The research on community consultation: an annotated bibliography

Acad Emerg Med

Research without consent: community perspectives from the Community VOICES Study

Acad Emerg Med

Exception from informed consent enrollment in emergency medical research: attitudes and awareness

Acad Emerg Med

Clinical paper
Enrollment in research under exception from informed consent: The Patients’ Experiences in Emergency Research (PEER) study☆