Public Approval of Exception From Informed Consent in Emergency Clinical Trials: A Systematic Review of Community Consultation Surveys
Original Investigation
William B. Feldman,  Spencer P. Hey,  Jessica M. Franklin, Aaron S. Kesselheim
JAMA Network Open, 24 July 2019; 2(7)
Open Access
Abstract
Importance  
The US Food and Drug Administration (FDA) created the exception from informed consent (EFIC) pathway in 1996 to allow some emergency trials to enroll patients without informed consent. To protect individual autonomy and preserve public trust, the FDA requires that EFIC trial investigators consult with community members before a trial may begin.
Objectives  
To analyze data from surveys conducted as part of community consultation ahead of EFIC trials and assess levels of public approval.
Data Sources  
All trials granted an EFIC must submit documentation of compliance with EFIC regulations to a publicly available docket at the FDA. Submissions between November 1, 1996, and October 23, 2017, were reviewed.
Study Selection  
Trials with survey data were included.
Data Extraction and Synthesis  
Data were extracted between January 2018 and June 2018 and were analyzed between June 2018 and August 2018. The quality and validity of data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A random-effects metaregression was used to assess the association of demographic characteristics with EFIC approval.
Main Outcomes and Measures  
The primary study outcome was EFIC approval.
Results  
The FDA docket contained 15 958 pages of material with survey data for 42 448 individuals submitted by 27 trials. Public approval of EFIC varied by question type, with more people willing to approve initiation of EFIC trials in their community (86.5%) than personal enrollment (73.0%), enrollment of a family member (68.6%), or the principle of enrollment without consent (58.4%) (P < .001 for all comparisons). In the United States, African American individuals made up 29.3% of those enrolled in EFIC trials that reported data on race (5064 of 17 302) but only 16.7% of those surveyed as part of community consultation. In the United States and Canada, men made up 42.9% of the surveyed population but 65.6% of those eventually enrolled in EFIC trials (29 961 of 45 694). Groups surveyed with higher proportions of African American and male respondents had lower rates of EFIC approval.
Conclusions and Relevance  
Public approval of EFIC trials varied by question type and by the respondents’ reported race and sex. The demographic characteristics of those surveyed did not match the demographic characteristics of EFIC enrollees. The FDA could strengthen community consultation by standardizing survey instruments and reporting, requiring broader inclusion of African American and male respondents, clarifying the function of surveys in the development and modification of trial protocols, and building more public consensus around the acceptable use of EFIC.

How Should We Apply the Wisdom of the Crowd to Clinical Trials With Exception From Informed Consent?
Invited Commentary 
Michael J. Lanspa, Eddy Fan, Alan H. Morris
JAMA Network Open, 24 July 2019; 2(7)
Open Access
Excerpt
In emergency trials applying for an exception from informed consent (EFIC), the US Food and Drug Administration (FDA) requires transparency, achieved through consultation with community members, before clinical investigators can enroll patients without informed consent. Feldman et al1 provide a review of surveys intended to achieve these consultations. Their results contribute to the literature by indicating the persistent gap between our goals and the imperfect surveys that have been reported…

Public Deliberation as a Novel Method for an Exception from Informed Consent Community Consultation
Original Contribution
Patricia E. Powers, Karen K. Shore, Susan Perez, Dominique Ritley, Nathan Kuppermann, James F. Holmes, Leah S Tzimenatos, Hiwote Shawargga, Daniel K. Nishijima
Academic Emergency Medicine, 4 July 2019
Abstract
Objectives
Community consultation is required for clinical trials considering federal exception from informed consent (EFIC) procedures. Questions remain about the value of the community consult process and whether it adds intended protections to study subjects. Public deliberation methods that provide baseline participant education and elicit values and opinions about consent options is a novel approach for community consultation. This study evaluated the use of structured public deliberation methods to assess a community’s values and opinions about informed consent procedures for a pediatric trauma trial.
Methods
This was a mixed‐methods descriptive study of public deliberation sessions assessing participants’ opinions about informed consent procedures for a pediatric trauma randomized controlled trial (RCT). Participants from communities with high rates of pediatric trauma were recruited via community‐based organizations and social media. Deliberation focused on three consent options for a proposed RCT: 1) enrollment using EFIC procedures with no attempt to obtain informed consent; 2) enrollment using EFIC procedures after attempting to reach a parent; or 3) enrollment only with informed consent. Participant demographic data and their opinions about the proposed study and deliberative session were also collected.
Results
There were 102 participants across eight sessions (range of 9 to 15/session, average of 13). Most participants were female (n=78, 76%) and a plurality black (n=48, 47%). The majority of participants preferred enrollment using EFIC procedures only after an attempt was made to reach a parent and informed consent was not possible (n=56, 55%), followed by enrollment using EFIC procedures with no attempt to obtain informed consent (n=32, 32%), and enrollment only with written informed consent (n=13, 13%). One participant declined all options. 84 participants (82%) agreed or strongly agreed that the RCT was important to do, and 79 participants (77%) said the sessions provided enough information to make an informed decision about the proposed RCT.
Conclusions
Structured public deliberation is an effective approach when consulting communities for trials considering EFIC procedures. Future studies are needed to evaluate whether public deliberation methods provide participants with enhanced understanding of clinical trials compared to other community consultation methods.

The impact of central IRB’s on informed consent readability and trial adherence in SPRINT
Leonardo Tamariz, Mitscher Gajardo, Carolyn H.Still, Lisa H.Gren, Elizabeth Clark, Sandy Walsh, Jeff Whittle, John Nord, Thomas Ramsey, Gabriel Contreras
Contemporary Clinical Trials Communications, September 2019; 15
Open Access
Abstract
Background
Federal agencies have encouraged the use of central institutional review boards (CIRBs) for multi-site clinical trials. There is limited evidence supporting the use of CIRBs. Our aim is to evaluate how SPRINT sites regulated by CIRBs performed regarding informed consent readability and participant trial adherence compared to those regulated by local IRBs.
Methods
We conducted a cohort study using the SPRINT clinical trial. We collected the IRB of record from the stamped and approved 2012 informed consents from each of the sites. We defined CIRB as an IRB for more than one SPRINT site. Our outcomes were informed consent readability measured using the Flesch-Kincaid readability scale and trial adherence defined as a loss to follow-up, consent withdrawal, and missed last 3-month visit.
Results
Sixty-one percent of all SPRINT sites used a CIRB as their IRB of record. The adjusted mean grade reading level for CIRB consents was 13.4 (95% CI 12.6–13.8) compared to 12.3 (95% CI 12.1–13.1) for non CIRB consents (p = 0.07). CIRB sites had similar rates of withdrawal of consent and loss to follow-up as non-CIRB sites; subjects missing the last appointment of the study were more likely to come from sites regulated by a CIRB. The Veterans Affairs CIRB had the lowest rate of withdrawal of consent (1.9%) and the lowest rate of missed appointments (1.9%) among CIRBs.
Conclusions
Niether CIRB-regulated sites nor IRB regulated sites enforce the recommended readability level of the informed consent documents. Sites regulated by both IRBs had similar participant trial adherence.

Editor’s note: SPRINT refers to the Systolic Blood Pressure Intervention Trial (SPRINT), a multisite randomized controlled trial.

What are research nurses’ experiences of obtaining consent from or for patients participating in emergency care research? A qualitative review
Review
Pauline Brown, Alistair Hewison, Roger Newham
Journal of Clinical Nursing, 26 June 2019
Abstract
Introduction
If studies are to be valid, recruitment of representative samples is essential. In 2012, 28% of UK emergency departments met the 80% standard for recruitment to trials set by the National Institute for Health Research. Research nurses play a vital role in the conduct of high‐quality research, and it has been argued that dedicated research nurses are needed if clinical trials are to recruit successfully to target.
Review question
What are research nurses’ experiences of obtaining consent from or for patients participating in emergency care research? A qualitative evidence review.
Methods
A qualitative integrative literature review with a narrative synthesis of the evidence. PRISMA guidelines for reporting systematic qualitative reviews (Appendix S1) were followed. A search of five electronic databases was performed in December 2018 along with a hand search which yielded 125 citations: 10 papers and one PhD thesis met the review eligibility criteria. Methodological quality of the selected studies was evaluated, and data were extracted and synthesised.
Results
Three themes were identified: Access, Organisation and Timing. Research nurses encountered both general and specific barriers when seeking to obtain consent for participation in research. In particular, it was found there was lack of experience among staff of working in emergency research and with securing deferred consent. The distinction between nurse researchers with a clinical role and those dedicated to solely to research only is often not clear and warrants further investigation.
Conclusion
Nurse researchers with and without a clinical role can make a positive difference in recruitment to trials in emergency care. The involvement of dedicated research nurses in the consent process can increase recruitment to emergency care research. Experience of recruiting to clinical trials in nonemergency settings does not seem to help when recruiting for trials in emergency care.
Relevance to clinical practice
There is a need for greater understanding of the experiences of dedicated research nurses in emergency care settings and in particular with regard to deferred consent.

Health literacy and informed consent for clinical trials: a systematic review and implications for nurses
Allison C Burks, Jessica Keim-Malpass
Nursing Research and Reviews, 2019; 9 pp 31-40
Open Access
Abstract
The informed consent process for consideration of clinical trials is a complex process that requires the understanding of the potential trial risk, benefits, and alternatives of treatment. The aim of this systematic review was to explore the available literature related to health literacy and the informed consent process for clinical trials. Articles were included if they focused on health literacy and patient comprehension of informed consent, had perceptions related to the informed consent process, or assessed the impact of health literacy on patients’ willingness to participate in clinical trials. Eight articles were selected for this review. Limited health literacy was determined to be related to a lack of comprehension of clinical trial consent documents and heightened anxiety surrounding the informed consent process. Conflicting evidence exists around the relationship between health literacy and clinical trial enrollment. Limited health literacy levels may impact the ability for nurses to have effective informed consent processes.

Improvement of Informed Consent Document Management in Clinical Trials Using an Electronic Medical Record System
Takahiro Kawakami, Katsuhiko Nagase, Yuko Yokoi, Yoshimichi Sai, Toshinori Murayama
Clinical Pharmacology, 2019; 50(3) pp 81-86
Abstract
Background
This study aims to systematize quality assurance and document management support to ensure the smooth implementation of investigator-initiated clinical trials (IITs).
Methods
A sample survey was performed to investigate whether and how signed original informed consent (IC) documents for IITs were stored at Kanazawa University Hospital. Based on the findings, initiatives were implemented utilizing an electronic medical record (EMR) system: 1) The latest versions of IC forms were issued directly from the EMRs for version control. Forms were printed with a 2D barcode to facilitate their re-entry into subjects’ medical records. 2) A new management protocol was introduced in the clinical trial support office to ensure consistent uploading processes for signed IC documents and the archiving of paper records. 3) Patients were registered to trials individually using their EMRs, enabling investigators to access their consent and progress statuses in one place. After implementing these initiatives, the storage of signed original IC documents was re-assessed.
Results
The EMR system presented a simpler IC document management compared to the conventional approach. The updated post-consent document handling procedure improved and consolidated signed original IC document archiving. In addition to the separate registration of trial subjects, investigators responsible for the trial were explicitly identified in the EMR system in the event of uncertainty in other departments. This approach allows for easy confirmation of subjectsʼ consent status when preparing and administering trial drugs.
Conclusions
Our approach of consolidated document and trial process management can improve the reliability of clinical research.

Editor’s note: This a Japanese language publication. Kanazawa University Hospital operates in Kanazawa, Ishikawa, Japan.