Exception From Informed Consent: How IRB Reviewers Assess Community Consultation and Public Disclosure
Research Article
Makini Chisolm-Straker, Denise Nassisi, Mohamud R. Daya, Jennifer N.B. Cook, Ilene F. Wilets, Cindy Clesca, Lynne D. Richardson
AJOB Empirical Bioethics, 29 September 2020
Abstract
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.

An audit of questions asked by participants during the informed consent process for regulatory studies at a tertiary referral centre – An analysis of consent narratives
Research Article
Unnati Saxena, Debdipta Bose, Mitesh Kumar Maurya, Nithya Jaideep Gogtay, Urmila Mukund Thatte
Clinical Ethics, 20 September 2020
Abstract
Objective
To evaluate the questions asked during the informed consent process by adult and adolescent participants as well as their parents in five interventional regulatory studies conducted at our center from 2018 to 2019.
Methods
The study protocol was approved by Institutional Ethics Committee [EC/OA-116/2019]. Consent narratives in the source documents for the studies were evaluated. Questions asked were classified as per Indian Council of Medical Research’s (ICMR) guidelines (2017). We evaluated total number of questions, nature of questions and whether there was an association between education, gender, phase of trials, physician taking consent and number questions being asked.
Results
A total of five studies that had N = 297 consent narratives were evaluated. Narratives of n = 284 adult participants/Guardians and of n = 13 children were analysed. A total of 374 questions were asked of which children asked only 10 questions. A total of 131/284 (40%) of the participants did not ask any question. Among the participants who asked questions, the majority132/171 (77%) participants asked about risks related to investigational products followed by questions related to study procedures 83/171 (49%). Participants/guardians with higher education (relative to those who were educated upto the secondary school and primary school) and those who consented for Phase III studies (relative to Phase I studies) asked significantly more questions (p < 0.0001).
Conclusion
A majority of the queries were related to the risks associated with the investigational products. Educational status and the Phase of the trial were found to be significantly associated with the number of questions being asked.

Characteristics Associated With Consent and Reasons for Declining in a Randomized Trial in Pregnancy
Original Research
Gail Mallett, Kim Hill, Jessica de Voest, Sabine Bousleiman, Donna Allard, Stacy Harris, Ashley Salazar, Kelly Clark, Felecia Ortiz, Anna Bartholomew, Wendy Dalton, Jennifer Craig, Melissa Bickus,
Obstetrics & Gynecology, 10 September 2020
Abstract
Objective
To evaluate the maternal characteristics associated with consent to a randomized trial of labor induction in pregnancy.
Methods
This is a secondary analysis of low-risk nulliparous women randomized to induction of labor at 39 weeks or expectant management. During the trial, the Data and Safety Monitoring Committee requested additional fields on the screening log, which already included race and ethnicity: maternal age, type of insurance, and the reason for declining consent if declined.
Results
From August 2016 (start of additional data collection) to August 2017, 1,965 (28%) of the 7,112 eligible women consented to the trial. Consent was more likely for Black women (41%, adjusted odds ratio [aOR] 1.47, 95% CI 1.24–1.74), and less likely for Asian women (15%, aOR 0.64, 95% CI 0.48–0.84), compared with White women (24%). Women without private insurance were more likely to consent (38%, aOR 1.55, 95% CI 1.34–1.79), compared with those with private insurance (22%). Younger women were also more likely to consent. Among eligible women who declined participation and provided a reason (68%), preference to be expectantly managed (85%) was most common, a response more common in Asian women (aOR 1.75, 95% CI 1.31–2.33) and less common in women without private insurance (aOR 0.60, 95% CI 0.51–0.70). Not wanting to participate in research was more common in Asian women (aOR 2.41, 95% CI 1.44–4.03). Declining consent because family or friends objected was more common in Asian women (aOR 2.51, 95% CI 1.27–4.95) and women without private insurance (aOR 1.68, 95% CI 1.10–2.59).
Conclusion
Frequency of consent and reasons for declining consent were associated with age, type of insurance, and race and ethnicity. These findings should be considered when developing recruitment strategies that promote diverse participant representation.

The Informed Consent Process in Health Research with Under-served Populations: A Realist Review Protocol
Eleanor Hoverd, Sophie Staniszewska, Jeremy Dale
Research Square, 9 September 2020
Open Access
Abstract
Background
The informed consent process aims to provide potential participants with information about health research that enables them to make an informed decision as to whether they choose to participate, or not. However, it remains unclear as to whether the process is effective for those whom are under-served in health research. It is a pivotal issue within health research that the diversity of people who participate is broadened. The National Institute for Health Research (NIHR) pledges to support equality, diversity and inclusion, actively creating opportunities for all citizens whom are eligible, to take part in health research.
Methods
In order to understand how the informed consent process for under-served populations in health research works, under what circumstances and in what respects, a realist review approach will be undertaken. Searches will be carried out using electronic databases (EMBASE, MEDLINE, Web of Science and PsychInfo), along with selected websites and grey literature. Development of initial rough programme theory(ies) will lead to a more refined programme theory that will provide an explanation of context, mechanism and outcomes. Stakeholder involvement by NIHR (Public) Research Champions, health professionals and clinical academics will provide expert opinion about concepts and programme theory.
Discussion
Findings of this realist review will highlight how the informed consent process in health research affects the experience and decision-making process of potential participants from under-served populations. They will be written up in accordance with RAMESES guidelines and disseminated to patients and the public, health researchers, health professionals and policymakers through peer-reviewed publication, presentations and discussions. The review will contribute to our understanding of the mechanisms that trigger both positive and negative outcomes in the informed consent process for those whom are often under-represented in health research to inform policy, study design and delivery.

Readability and understandability of clinical research patient information leaflets and consent forms in Ireland and the UK: a retrospective quantitative analysis
Original Research
Lydia O’Sullivan, Prasanth Sukumar, Rachel Crowley, Eilish McAuliffe, Peter Doran
Ethics, 3 September 2020
Abstract
Objectives
The first aim of this study was to quantify the difficulty level of clinical research Patient Information Leaflets/Informed Consent Forms (PILs/ICFs) using validated and widely used readability criteria which provide a broad assessment of written communication. The second aim was to compare these findings with best practice guidelines.
Design
Retrospective, quantitative analysis of clinical research PILs/ICFs provided by academic institutions, pharmaceutical companies and investigators.
Setting
PILs/ICFs which had received Research Ethics Committee approval in the last 5 years were collected from Ireland and the UK.
Intervention
Not applicable.
Main outcome measures
PILs/ICFs were evaluated against seven validated readability criteria (Flesch Reading Ease, Flesh Kincaid Grade Level, Simplified Measure of Gobbledegook, Gunning Fog, Fry, Raygor and New Dale Chall). The documents were also scored according to two health literacy-based criteria: the Clear Communication Index (CCI) and the Suitability Assessment of Materials tool. Finally, the documents were assessed for compliance with six best practice metrics from literacy agencies.
Results
A total of 176 PILs were collected, of which 154 were evaluable. None of the PILs/ICFs had the mean reading age of <12 years recommended by the American Medical Association. 7.1% of PILs/ICFs were evaluated as ‘Plain English’, 40.3%: ‘Fairly Difficult’, 51.3%: ‘Difficult’ and 1.3%: ‘Very Difficult’. No PILs/ICFs achieved a CCI >90. Only two documents complied with all six best practice literacy metrics.
Conclusions
When assessed against both traditional readability criteria and health literacy-based tools, the PILs/ICFs in this study are inappropriately complex. There is also evidence of poor compliance with guidelines produced by literacy agencies. These data clearly evidence the need for improved documentation to underpin the consent process.

Seven-step framework to enhance practitioner explanations and parental understandings of research without prior consent in paediatric emergency and critical care trials
Original Research
Louise Roper, Mark D Lyttle, Carrol Gamble, Amy Humphreys, Shrouk Messahel, Elizabeth D Lee, Joanne Noblet, Helen Hickey, Naomi Rainford, Anand Iyer, Richard Appleton
BMJ Emergency Medicine Journal, 29 August 2020
Abstract
Background
Alternatives to prospective informed consent enable the conduct of paediatric emergency and critical care trials. Research without prior consent (RWPC) involves practitioners approaching parents after an intervention has been given and seeking consent for their child to continue in the trial. As part of an embedded study in the ‘Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children’ (EcLiPSE) trial, we explored how practitioners described the trial and RWPC during recruitment discussions, and how well this information was understood by parents. We aimed to develop a framework to assist trial conversations in future paediatric emergency and critical care trials using RWPC.
Methods
Qualitative methods embedded within the EcLiPSE trial processes, including audiorecorded practitioner–parent trial discussions and telephone interviews with parents. We analysed data using thematic analysis, drawing on the Realpe et al (2016) model for recruitment to trials.
Results
We analysed 76 recorded trial discussions and conducted 30 parent telephone interviews. For 19 parents, we had recorded trial discussion and interview data, which were matched for analysis. Parental understanding of the EcLiPSE trial was enhanced when practitioners: provided a comprehensive description of trial aims; explained the reasons for RWPC; discussed uncertainty about which intervention was best; provided a balanced description of trial intervention; provided a clear explanation about randomisation and provided an opportunity for questions. We present a seven-step framework to assist recruitment practice in trials involving RWPC.
Conclusion
This study provides a framework to enhance recruitment practice and parental understanding in paediatric emergency and critical care trials involving RWPC. Further testing of this framework is required.

Evaluating the Quality of Research Ethics Review and Oversight: A Systematic Analysis of Quality Assessment Instruments
Holly Fernandez Lynch, Mohamed Abdirisak, Megan Bogia, Justin Clapp
American Journal of Bioethics, 21 August 2020
Abstract
Background
Research ethics review committees (RERCs) and Human Research Protection Programs (HRPPs) are responsible for protecting the rights and welfare of research participants while avoiding unnecessary inhibition of valuable research. Evaluating RERC/HRPP quality is vital to determining whether they are achieving these goals effectively and efficiently, as well as what adjustments might be necessary. Various tools, standards, and accreditation mechanisms have been developed in the United States and internationally to measure and promote RERC/HRPP quality.
Methods
We systematically reviewed 10 quality assessment instruments, examining their overall approaches, factors considered relevant to quality, how they compare to each other, and what they leave out. For each tool, we counted the number of times each of 34 topics (divided into structure, process, and outcome categories) was mentioned. We generated lists of which topics are most and least mentioned for each tool, which are most prevalent across tools, and which are left unmentioned. We also conducted content analysis for the 10 most common topics.
Results
We found wide variability between instruments, common emphasis on process and structure with little attention to participant outcomes, and failure to identify clear priorities for assessment. The most frequently mentioned topics are Review Type, IRB Member Expertise, Training and Educational Resources, Protocol Maintenance, Record Keeping, and Mission, Approach, and Culture. Participant Outcomes is unmentioned in 8 tools; the remaining 2 tools include assessments based on adverse events, failures of informed consent, and consideration of participant experiences.
Conclusions
Our analysis confirms that RERC/HRPP quality assessment instruments largely rely on surrogate measures of participant protection. To prioritize between these measures and preserve limited resources for evaluating the most important criteria, we recommend that instruments focus on elements relevant to participant outcomes, robust board deliberation, and procedures most likely to address participant risks. Validation of these approaches remains an essential next step.

Food and Drug Administration and Institutional Review Board Approval of a Novel Prehospital Informed Consent Process for Emergency Research
Jason McMullan,Christopher Droege,Col. Richard Strilka, Christopher Lindsell, Michael J. Linke
Prehospital Emergency Care, 13 August 2020
Abstract
Research on the management of acute pain in the prehospital setting is fraught with challenges. The prehospital setting is complex due to constrained time, resources, and training. Research activities must not interfere with the underlying clinical priorities of immediate patient stabilization and rapid transport to an appropriate hospital. The patient’s pain, fear, and anxiety immediately after a traumatic event may interfere with undertaking an adequate informed consent process.

Pain management trials do not satisfy the criteria for application of the U.S. Food and Drug Administration (FDA) 21 CFR 50.24 exception from informed consent. While non-standard informed consent processes exist, waiver or alteration of informed consent may be limited if Institutional Review Boards or the FDA consider these studies to involve more than minimal risk related to the setting of the study, even if the interventions themselves might involve no more than minimal risk in other settings. In addition, any study requiring an Investigational New Drug application requires fully documented standard informed consent.

Emergency Medical Services agencies and fire departments become research institutions, and paramedics become study staff, but both the institutions and the staff often lack experience conducting human subjects research and are rarely formally affiliated with the academic institution overseeing the research. As such, additional administrative burdens must be overcome in interventional prehospital studies, including additional training in the study protocol, research operations, and human subjects protections. Institutions conducting federally funded studies commit to regulations covering human subjects protections in the form of a Federalwide Assurance (FWA); prehospital organizations participating in research must either obtain an FWA or have coverage extended to them from an academic partner.

We describe how these challenges were addressed during Institutional Review Board review and approval of an FDA-regulated randomized placebo-controlled trial of intranasal ketamine (vs. placebo) in acutely injured patients receiving standard of care fentanyl for prehospital pain management (NCT02866071). To our knowledge, this trial is the first instance in the United States of paramedics screening, consenting, enrolling, and administering study medications to patients without direct, real-time support from a dedicated clinical research team.

Study within a trial protocol: Same‐day consent vs. delayed consent in a randomized trial
Marah Elfghi, Fionnuala Jordan, Sherif Sultan, Wael Tawfick
Journal of Evidence-Based Medicine, 15 June 2020
Abstract
Background
Randomized trials are designed to evaluate the effects of health care interventions. The recruitment process in a randomized trial can be challenging. Poor recruitment can have a negative impact on the allocated budget and estimated completion date of the study and may result in an underpowered research that will not adequately answer the original research question.
Aim
We aim to perform a Study Within A Trial (SWAT) to evaluate the impact of same‐day consent or delayed consent on recruitment and retention in the host trial.
Methods
This SWAT is designed as an observational study. However, the host trial is a randomized controlled trial evaluating the effectiveness of an intensive lifestyle modification program in patients with peripheral arterial disease. For this trial and SWAT, same‐day consent is defined as the patient giving consent on the same day, after the investigator has fully explained the predesigned information leaflet for the host trial. Delayed consent is defined as the patient feeling they still need further time to consider their decision to participate or not.

Towards Identifying an Upper Limit of Risk: A Persistent Area of Controversy in Research Ethics
Erin T. Paquette, Seema K. Shah
Perspectives in Biology and Medicine, Spring 2020; 63(2)
Abstract
Whether there is an upper limit of net risk that volunteers can consent to in research, and what that limit happens to be, has been the subject of persistent controversy in research ethics. This article defends the concept of an upper limit of risk in research against recent critics and supports the most promising approach for identifying this limit, that of finding comparator activities that are generally accepted in society and pose high levels of risk. However, high-risk activities that have been proposed as relevant comparators involve more certain benefits and confer considerable social esteem to those who take on the risks. This suggests that developing a robust approach to identifying social value, whether by developing a procedural safeguard or a systematic framework, could more effectively identify research with sufficient social value to justify high net risk. Additionally, the social status of research participants should be elevated to be more on par with others who laudably take on high risk for the benefit of others. By attending to the benefits necessary for the justification of high-risk research, the level of allowable risk will no longer be so controversial.