Informed Consent: A Monthly Review

April 2021

This digest aggregates and distills key content addressing informed consent from a broad spectrum of peer-reviewed journals and grey literature, and from various practice domains and organization types including international agencies, INGOs, governments, academic and research institutions, consortiums and collaborations, foundations, and commercial organizations. We acknowledge that this scope yields an indicative and not an exhaustive digest product.

Informed Consent: A Monthly Review is a service of the Center for Informed Consent Integrity, a program of the GE2P2 Global Foundation. The Foundation is solely responsible for its content. Comments and suggestions should be directed to:

Paige Fitzsimmons, MA
Associate Director, Center for Informed Consent Integrity
GE2P2 Global Foundation
PDF Version: GE2P2 Global_Informed Consent – A Monthly Review_April 2021

Editor’s Note:
Informed consent for neonatal trials – Practical points to consider
was the latest webinar in the Center’s continuing series held on March 17th 2021. The invited speakers were Dr. Beate Aurich of the Institut National de la Santé et de la Recherche Médicale (INSERM) in Paris, France, and Dr. Eric Vermeulen of the Dutch Patient Association for Rare and Genetic Diseases (VSOP) in Soest, The Netherlands. The presentation was followed by a rich discussion with call participants regarding areas such as parental consent, assent and reconsent, and the role of patient and parent involvement in trials and the design of the informed consent process.

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic

Informed consent and a risk-based approach to oncologic surgery in a cancer center during the COVID-19 pandemic
de Cássio Zequi S, Franca Silva ILA, Duprat JP, Coimbra FJF, Gross JL, Vartanian JG, Makdissi FBA, Leite FPM, Costa WHD, Yazbek G, Joaquim EHG, Bussolotti RM, Caruso P, de Ávila Lima MC, Nakagawa S, Aguiar S Jr, Baiocchi G, Lopes A, Kowalski LP
Journal of Surgical Oncology, 7 March 2021
Open Access
Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC).
To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak.
We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program.
Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed.
During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

Waivers and Alterations of Research Informed Consent During the COVID-19 Pandemic

Waivers and Alterations of Research Informed Consent During the COVID-19 Pandemic
Ideas and Opinions
Emily A. Largent, Scott D. Halpern, Holly Fernandez Lynch
Annals of Internal Medicine, March 2021
Open Access
A foundational requirement of ethical research is that persons provide informed consent. Yet, there are exceptions that promote valuable research without unduly compromising participants’ interests. Applicable regulations for federally funded research permit waiver or alteration of consent requirements when certain conditions are met, including that the research poses no more than minimal risk to participants and that it would be impracticable to do without waiver or alteration (1). Determining whether these regulatory standards are met has become increasingly challenging during the coronavirus disease 2019 (COVID-19) pandemic…

Refusal rates and waivers of informed consent in pragmatic and comparative effectiveness RCTs: A systematic review

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
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.
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.
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.
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)

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
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.
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)%.
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.
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

Distinctive aspects of consent in pilot and feasibility studies
Original Paper
Julius Sim
Journal of Evaluation in Clinical Practice, 24 February 2021
Open Access
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

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
    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

Nano-drug Clinical Trials: Informed Consent and Risk Management Through Blockchain
Yousef Haik, Ilias Bantekas
Pittsburgh Journal of Technology Law & Policy, 2021
Open Access
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.

“Why didn’t we do it”? Reproductive loss and the problem of post-mortem consent

“Why didn’t we do it”? Reproductive loss and the problem of post-mortem consent
Kate Reed, Maria Teresa Ferazzoli, Elspeth Whitby
Social Science & Medicine, 12 March 2021
Informed consent has been a much debated topic within the social sciences. It often forms a central feature of discussions on research in medical settings and in social research methods more broadly. While sympathetic to its’ underlying principles of autonomy and choice, social scientists have tended to argue that these are seldom enacted in research or clinical practice. Rather, such principles are often circumscribed by wider social structures and by a culture of medical dominance. Drawing on data from a qualitative study on perinatal post-mortem, this paper explores informed consent in the emotionally charged clinical arena of perinatal pathology. Our in-depth analysis will provide fresh insight into post-mortem decision-making in the sensitive arena of baby loss. Our findings show how parents often found it difficult to give consent for post-mortem, and also for professionals to take consent from parents. It was also not uncommon for parents to experience regret over non-consent later on. One of our key findings, however, related to the sense of emotional and diagnostic closure often afforded by post-mortem when consent had been given. We conclude by arguing that, although we cannot resolve the tension between the principles of consent and their enactment in practice, we can develop a reflexive approach with which to navigate the process. In doing so, the paper contributes to wider sociological discussions on the meaning and use of informed consent in various settings beyond medical contexts.

Mainstreaming informed consent for genomic sequencing: A call for action

Mainstreaming informed consent for genomic sequencing: A call for action
Current Perspective
Eline M. Bunnik, Wybo J. Dondorp, Annelien L. Bredenoord, Guido de Wert, Martina C. Corneld
European Journal of Cancer, May 2021; 148 pp 405-410
The wider availability of genomic sequencing, notably gene panels, in cancer care allows for personalised medicine or the tailoring of clinical management to the genetic characteristics of tumours. While the primary aim of mainstream genomic sequencing of cancer patients is therapy-focussed, genomic testing may yield three types of results beyond the answer to the clinical question: suspected germline mutations, variants of uncertain significance (VUS), and unsolicited findings pertaining to other conditions. Ideally, patients should be prepared beforehand for the clinical and psychosocial consequences of such findings, for themselves and for their family members, and be given the opportunity to autonomously decide whether or not to receive such unsolicited genomic information. When genomic tests are mainstreamed into cancer care, so should accompanying informed consent practices. This paper outlines what mainstream oncologists may learn from the ethical tradition of informed consent for genomic sequencing, as developed within clinical genetics. It argues that mainstream informed consent practices should focus on preparing patients for three types of unsolicited outcomes, briefly and effectively. Also, it argues that when the chance of unsolicited findings is very low, opt-out options need not be actively offered. The use of a layered approach – integrated in information systems – should render informed consent feasible for non-geneticist clinicians in mainstream settings. (Inter) national guidelines for mainstreaming informed consent for genomic sequencing must be developed.