Rethinking consent processes for research in emergency departments
Perspective
Joseph Miller, Stephen Guy Costa,  David Alan Taylor, Paul Buntine
Emergency Medicine Australasia, 17 April 2021
Abstract
Emergency medicine researchers face the challenge of prioritising patients’ immediate interests and maintaining hospital flow while attempting to collect clinical data. Even in low‐risk scenarios, excessive consent processes can make it difficult to recruit patients while observing guidelines on efficient triage. We discuss a recent situation in which a six‐page consent form appeared to deter clinicians from recruiting patients to a low‐risk intervention. We then argue that there need be no conflict between the imperatives of patient wellbeing and clinical research. Apparent conflicts between treatment and research could be reduced through creative recruitment techniques: the adoption of an ‘opt‐out’ approach; securing the budget for a dedicated research assistant; early consultation with the institution’s human research ethics committee; and the use of a short, simple participant information and consent form with a QR code linking to a more detailed outline of the study.

Transparency of informed consent in pilot and feasibility studies is inadequate: a single-center quality assurance study
Research
Mohammed I.U. Khan, Lawrence Mbuagbaw, Matthew Holek, Faris Bdair, Zoha H. Durrani, Katie Mellor, Saskia Eddy, Sandra M. Eldridge, Claire L. Chan, Michael J. Campbell, Christine M. Bond, Sally Hopewell, Gillian A. Lancaster, Lehana Thabane
Pilot and Feasibility Studies, 16 April 2021; 7(96)
Open Access
Abstract
Background
Pilot and feasibility studies (PAFS) often have complex objectives aimed at assessing feasibility of conducting a larger study. These may not be clear to participants in pilot studies.
Methods
Here, we aimed to assess the transparency of informed consent in PAFS by investigating whether researchers communicate, through patient information leaflets and consent forms, key features of the studies. We collected this data from original versions of these documents submitted for ethics approval and the final approved documents for PAFS submitted to the Hamilton Integrated Research Ethics Board, Canada.
Results
One hundred eighty-four PAFS, submitted for ethics approval from 2004 to 2020, were included, and we found that of the approved consent documents which were provided to participants, 83.2% (153) stated the terms “pilot” or “feasibility” in their title, 12% (22) stated the definition of a pilot/feasibility study, 42.4% (78) of the studies stated their intent to assess feasibility, 19.6% (36) stated the specific feasibility objectives, 1.6% (3) stated the criteria for success of the pilot study, and 0.5% (1) stated all five of these criteria. After ethics review, a small increase in transparency occurred, ranging from 1.6 to 2.8% depending on the criteria. By extracting data from the protocols of the PAFS, we found that 73.9% (136) stated intent to assess feasibility, 71.2% (131) stated specific feasibility objectives, and 33.7% (62) stated criteria for success of the study to lead to a larger study.
Conclusion
The transparency of informed consent in PAFS is inadequate and needs to be specifically addressed by research ethics guidelines. Research ethics boards and researchers ought to be made aware and mindful of best practices of informed consent in the context of PAFS.

Under consent: participation of people with HIV in an Ebola vaccine trial in Canada
Research Article
Pierre-Marie David, Benjamin Mathiot, Oumy Thiongane & Janice E. Graham
BMC Medical Ethics, 9 April 2021; 22(42)
Open Access
Abstract
Background
Little is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate.
Methods
Observation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews were recorded, transcribed and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants’ stories to develop two ideal portraits based on “composite characters” based on study participants features. These provide ethnographically rich details of participants’ meaningful social worlds while protecting individual identities.
Results
Ten of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation.
Conclusions
Our findings support Fisher’s argument of “structural coercion” in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie “under consent” of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North.

Assessment of the Appropriateness of the i-CONSENT Guideline Recommendations for Improving Understanding of the Informed Consent Process in Clinical Studies
Fons-Martínez J, Ferrer-Albero C, Diez-Domingo J
Research Square, 5 April 2021
Abstract
Background
The H2020 i-CONSENT project has developed a set of guidelines that offer ethical recommendations and practical tools aimed at making the informed consent process in clinical studies more comprehensive, tailored, and inclusive. An analysis of the appropriateness of some of its novel recommendations was carried out by a group of experts representing different stakeholders.
Methods
An adaptation of the RAND/UCLA Appropriateness Method was used to assess the level of agreement on the recommendations among 14 representatives of different stakeholders, including patients, regulators, investigators, ethics experts, and the pharmaceutical industry. The process included two rounds of rating and a virtual meeting.
Results
Fifty-three recommendations were evaluated. After the first round, 34 recommendations were judged appropriate; 19 were judged uncertain; and none was judged inappropriate. After the second round, 9 uncertain changed to appropriate. All recommendations rated medians of 6.5-9 on a 1-9 scale (1 = extremely inappropriate, 5 = uncertain, 9 = extremely appropriate). The sections “General recommendations” and “Gender perspective during the consent process for clinical studies” showed the highest uncertainty rating. The four keys to improving the understanding of the ICP in clinical studies are to: (1) consider consent a two-way continuous interaction that begins at the first contact with the potential participant and continues until the end of the study; (2) improve investigators’ communication skills; (3) co-create the information; and (4) use a layered approach, including information to compensate for the potential participant’s possible lack of health literacy and a glossary of terms.
Conclusions
The RAND/UCLA method has demonstrated validity for assessing the appropriateness of recommendations in ethical guidelines. The recommendations of the i-CONSENT guidelines were mostly judged appropriate by all stakeholders involved in the informed consent process.

Framing a Consent Form to Improve Consent Understanding and Determine How This Affects Willingness to Participate in HIV Cure Research: An Experimental Survey Study
Research Article
John A. Sauceda, Karine Dubé, Brandon Brown, Ashley E. Pérez, Catherine E. Rivas, David Evans, Celia B. Fisher
Journal of Empirical Research on Human Research Ethics, 14 December 2020
Abstract
HIV cure research carries serious risks and negligible benefits. We investigated how participants understand these risks and what influences their willingness to participate. Through internet-based and in-person convenience sampling, 86 HIV+ participants completed an experimental survey. Participants were randomized to read a standard consent form describing a hypothetical HIV cure study or one adapted using Fuzzy Trace Theory—a decision-making model to facilitate complex information processing. We measured consent understanding and cognitive (e.g., safe/harmful) and affective (e.g., concerning, satisfying) evaluations of HIV cure research. Participants who read the adapted consent form had improved consent understanding, but only positive affective evaluations were associated with a willingness to participate. Consent processes can use decision-making theories to facilitate comprehension of study information.

Refusal rates and waivers of informed consent in pragmatic and comparative effectiveness RCTs: A systematic review
Lisa Y. Lin, Nicole Jochym, Jon F. Merz
Contemporary Clinical Trials, May 2021; 104
Abstract
Background
Pragmatic and comparative effectiveness randomized controlled trials (RCTs) aim to be highly generalizable studies, with broad applicability and flexibility in methods. These trials also address recruitment issues by minimizing exclusions. The trials may also appeal to potential subjects because of lower risk and lower burdens of participation. We sought to examine rates of refusal and uses of waivers of informed consent in pragmatic and comparative effectiveness RCTs.
Methods
A systematic review of pragmatic and comparative effectiveness RCTs performed wholely or in part in the United States and first published in 2014 and 2017.
Results
103 studies involving 105 discrete populations were included for review. Refusal data was collected for 71 RCTs. Overall, studies reported an average rate of 31.9% of potential subjects refused participation; on an individual basis, 38.4% of people asked to take part refused at some point during recruitment. 23 trials (22%) were performed, at least in part, with a waiver of informed consent, 7 (30%) of which provided any form of notice to subjects.
Conclusions
Overall refusal rates for pragmatic and comparative effectiveness RCTs appear roughly the same as other types of research, with studies reporting about a third of people solicited for participation refuse. Moreover, informed consent was waived in 22% (95% Binomial exact Confidence Interval 13.9–30.5%) of the trials, and further study is needed to understand when waivers are justified and when notice should be provided.

Patients Acceptance and Comprehension to Written and Verbal Consent (PAC-VC)
Research Article
Rabia Kashur, Justin Ezekowitz, Shane Kimber, Robert Welsh
BMC Medical Ethics, 2 March 2021
Open Access
Abstract
Background
Acute myocardial infarction (AMI) research is challenging as it requires enrollment of acutely ill patients. Patients are generally in a suboptimal state for providing informed consent. Patients’ understanding to verbal assents have not been previously examined in AMI research. Patients Acceptance and Comprehension to Written and Verbal Consent (PAC-VC) compared patients’ understanding and attitudes to verbal and written consents in AMI RCTs.
Methods
PAC-VC recruited patients from 3 AMI trials using both verbal N=12 and written N=6 consents. We compared patients’ understanding using two survey questionnaires. The first questionnaire used open ended questions with multiple choice answers. The second questionnaire used a 5-point Likert scale to measure patients understanding and attitudes to the consent process. Overall answers average scores were categorized into three groups: Adequate understanding (71-100) %, Partial understanding (41-70)% and Inadequate understanding (0-40)%.
Results
Responses showed patients with verbal assent had adequate understanding to most components of iinformed consent, close to those of written consent. Most patients did not read written information entirely and believed that it is not important to make a final decision. Patients favoured to have written information be part of the consent but not necessarily presented during the initial consent process. Patients felt less pressured in the verbal assent arm than those of written consent.
Conclusion
Patients had adequate understanding to most components of verbal assent and comparable to those of written consent. Utilizing verbal assents in the acute care setting should be further assessed in larger trials.

Distinctive aspects of consent in pilot and feasibility studies
Original Paper
Julius Sim
Journal of Evaluation in Clinical Practice, 24 February 2021
Open Access
Abstract
Prior to a main randomized clinical trial, investigators often carry out a pilot or feasibility study in order to test certain trial processes or estimate key statistical parameters, so as to optimize the design of the main trial and/or determine whether it can feasibly be run. Pilot studies reflect the design of the intended main trial, whereas feasibility studies may not do so, and may not involve allocation to different treatments. Testing relative clinical effectiveness is not considered an appropriate aim of pilot or feasibility studies. However, consent is no less important than in a main trial as a means of morally legitimizing the investigator’s actions. Two misperceptions are central to consent in clinical studies—therapeutic misconception (a tendency to conflate research and therapy) and therapeutic misestimation (a tendency to overestimate possible benefits and/or underestimate possible harms associated with participation). These phenomena may take a distinctive form in pilot and feasibility studies, owing to potential participants’ likely prior unfamiliarity with the nature and purposes of such studies. Thus, participants may confuse the aims of a pilot or feasibility study (developing or optimizing trial design and processes) with those of a main trial (testing treatment effectiveness) and base consent on this misconstrual. Similarly, a misunderstanding of the ability of pilot and feasibility studies to provide information that will inform clinical care, or the underdeveloped nature of interventions included in such studies, may lead to inaccurate assessments of the objective possibility of benefit, and weaken the epistemic basis of consent accordingly. Equipoise may also be particularly challenging to grasp in the context of a pilot study. The consent process in pilot and feasibility studies requires a particular focus, and careful communication, if it is to carry the appropriate moral weight. There are corresponding implications for the process of ethical approval.

Model Operational Procedures for the Implementation and Review of NIH Sponsored Multicenter Clinical Trials with Exception from Informed Consent (EFIC) for Emergency Research
SIREN Clinical Coordinating Center
Version 1, January 2021
Open Access
Introduction
    The purpose of this document is to provide a model process and procedures that can be used as starting point for implementation of clinical trials using Exception from Informed Consent for Emergency Research (EFIC) in NIH funded multicenter clinical trials. The process and procedures described can and must be adapted to the specific needs and details of any future trials. The materials provided were developed and informed by both thorough review of the accumulated scholarship related to EFIC, and other lessons learned through practical shared experiences of prior NIH funded emergency care researchers.
This document is intended to be a useful, practical, and tested peer-to-peer tool for future investigators in this field. It is not intended to be a definitive guideline for application of the EFIC regulations, and should NOT be interpreted as any form of regulatory guidance. Regulatory guidance is available from FDA. This document does not represent the only way to implement Exception from Informed Consent, and may not be applicable or optimal for EFIC studies that differ from those for which this document was created. This document is intended to be open access, and shared through a Creative Commons Attribution-NonCommercial (CC BY-NC) license that lets others adapt, and build upon the work non-commercially. New works must acknowledge the source materials and the NIH and be non-commercial. The derivative works do not have be licensed on the same terms.

Nano-drug Clinical Trials: Informed Consent and Risk Management Through Blockchain
Yousef Haik, Ilias Bantekas
Pittsburgh Journal of Technology Law & Policy, 2021
Open Access
Abstract
Drug bearing nano-shells that can be utilized for targeted drug delivery have been shown to enhance the therapeutic index by increasing the drug concentration in diseased tissue and reducing the toxicity in normal tissue. The controllability of the drug bearing shell size provides predictability measure for the amount of drug payload per shell which improves the administration of the therapeutic dose.  The FDA approved different formulations for clinical use in metastatic and recurrent breast cancer, among other diseases.  At the moment, some of these formulations are the subject of international clinical trials.  Informed consent is legally mandated in administering drug bearing nano-shells.  The risks of the new formulations, as with all new technologies, are not well known and continue to be a subject of intensive research, thus exacerbating the existing informed consent legal issues, thus exacerbating the existing informed consent legal issues.  This short essay focuses on proposing a framework to mitigate liabilities administering a new formulation on nano-enabled drug carriers particularly when uncertainties of the benefits and damages are not fully known.