Accelerating Randomized Trials (ART) Virtual Workshop (April 30, 2022), Schulich School of Medicine & Dentistry, Western University. Presentation #6 - Ethical considerations and practical tips: an REB perspective (Erika Basile): 15-min webinar.

• Summary: Erika Basile (Director of Research Ethics and Compliance, Western University) discusses ethical principles related to consent in research, with a specific focus on the regulatory requirements and REB considerations related to potential alterations to consent in pragmatic trials.

NIH Pragmatic Trials Collaboratory (Grand Rounds) - Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations (April 26, 2024): 43-min presentation & 17-min Q&A (39-slide presentation)

• Summary: Drs. Lauren Milner (Office of Clinical Policy at the US Food and Drug Administration), Jonathan Casey, and Matthew Semler discuss institutional review board waivers or alterations to informed consent for minimal risk studies that are regulated by the FDA. The discussion focuses specifically on how these developments may impact pragmatic trials. While the discussion refers to US-based regulations and terminology, the regulatory and ethical landscape in Canada share commonalities, and similar regulatory developments and ethical discussions are taking place in Canada. * Note: Researchers who do not intend to conduct FDA-regulated trials may still derive value from this webinar. Further, for those with interest in the specifics of these regulatory developments in the US - and how they may reflect potential future developments in Canada - there is a detailed “federal register” describing these developments here.

Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement (TCPS): Ethical Conduct for Research Involving Humans, December 2022. Chapter 3: The Consent Process (Article 3.7A - Alterations to Consent Requirements): 4-page section (pages 46-49)

• Summary: In specific circumstances, Article 3.7A - Alterations to Consent Requirements may be relevant to pragmatic trialists. i.e., An REB may approve research that involves an alteration to the requirements for consent if the REB is satisfied and documents that all of the following apply: a. The research involves no more than minimal risk to the participants; b. The alteration to consent requirements is unlikely to adversely affect the welfare of participants; c. It is impossible or impracticable to carry out the research and to address the research question properly, given the research design, if the prior consent of participants is required; d. In the case of a proposed alteration, the precise nature and extent of any proposed alteration is defined; and e. The plan to provide a debriefing (if any) that may also offer participants the possibility of refusing consent and/or withdrawing data and/or human biological materials, shall be in accordance with Article 3.7B - Debriefing in the Context of Alterations to Consent Requirements.

  • Researchers considering alterations to consent should begin by reviewing Article 3.7A, i.e., the guidance provided in the “Application” section and the glossary of terms (which includes, for example, definitions of “minimal risk,” “impracticable,” and “debriefing”).

  • As per Article 3.7A, “Alterations to consent should be permitted only to the extent necessary. If the aims of the research can be achieved with a design that allows for full - or fuller - prior disclosure, then that design must be adopted. It is the responsibility of REBs, however, to understand that certain research methods necessitate a different approach to consent, and to exercise judgment on whether the need for the research justifies any alterations to consent requirements.” * Note: It is recommended that researchers collaborate with their local REBs early in the design of their pragmatic trial to best navigate the ethical and regulatory considerations.

Accelerating Randomized Trials (ART) Virtual Workshop (April 30, 2022), Schulich School of Medicine & Dentistry, Western University. Presentation #5 - The ethics of pragmatic trials: common pitfalls and a way forward (Dr. Charles Weijer): 15-min webinar.

• Summary: Dr. Charles Weijer addresses several common ethical pitfalls in pragmatic trials and offers tips on how to avoid them. Pitfall #1: Failure to justify the use of cluster randomized designs; Pitfall #2: Failure to identify and protect vulnerable research participants; Pitfall #3: Failure to identify health providers as research participants; Pitfall #4: Wrongfully equating usual care with minimal risk; Pitfall #5: Conflating local treatment policy and a cluster-level intervention; Pitfall #6: False dichotomy between written informed consent and a waiver of consent.

Zhang JZ, et al. Informed consent in pragmatic trials: results from a survey of trials published 2014-2019. J Med Ethics. 2021 Nov 15:medethics-2021-107765. (7-page paper)

• Summary: Reports on a survey of published trials (2014-2019) and describes reporting of informed consent, justifications for waivers of consent, and reporting of alternative approaches to standard written consent. It is suggested that greater attention to alternative (REB-approved) consent approaches - beyond the dichotomy of a full waiver vs. standard written informed consent - may better preserve participant autonomy and the trust of patients and the public in research.

NEJM Interview: Charles Weijer on the potential benefits and ethical challenges associated with pragmatic and cluster RCTs (September 24, 2024 via "NEJM Group"): 12-min interview.

• Summary: Dr. Charles Weijer contrasts explanatory to pragmatic trials, describes pragmatism as relating to a researchers intention and question, and discusses a related perspective article (Weijer C & Taljaard M (2024); requires institutional login). This article overviews a hypothetical situation of a research team considering an altered approach to consent in a pragmatic cluster trial. The authors emphasize that pragmatic trials (particularly cluster trials evaluating individual-level interventions) raise several important ethical questions, and that navigating these considerations requires multidisciplinary expertise, meaningful partnerships, and patient/public engagement.

Fernandez Lynch H, Kramer DB. Facilitating Efficient and Ethical Trials at the Intersection of Research and Clinical Care. JAMA. 2025 Jan 7;333(1):34-36. (3-page editorial) * As this is an optional resource, an institutional login (e.g., university or research institute e-mail address) is required to access this material.

• Summary: This is an editorial on the Kass NE, et al. (2024) special communication included in the November 4, 2024 module as an optional resource. This editorial provides context as to why REBs currently struggle when research and clinical care are integrated together (as is often seen in pragmatic trials), explains why this is an opportune moment for change, and notes additional areas in which regulatory clarity is needed to support ethical goals.

Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement (TCPS): Ethical Conduct for Research Involving Humans, December 2022. Chapter 3: The Consent Process: 35-page chapter (pages 31-65)

• Summary: This chapter sets out the ethical requirements for consent in research involving humans in Canada. * Note: While Article 3.7A - Alterations to Consent Requirements (included in this chapter) is a primary resource in this module, a review of the entire chapter will be relevant for those who have not completed the TCPS 2: CORE-2022 training as a requirement of their research institution.