Making the Ethical Oversight of All Clinical Trials Fit for Purpose (Source) 

Importance: With the increase in trials assessing comparative effectiveness of approved products and alternative care strategies, guidance is needed to ensure ethical oversight is fit for purpose for the risks, burdens, and constraints on choice this research presents.

Observations: US regulations governing human research emerged in response to horrific research abuses, reinforcing the view that research holds greater risks, uncertainties, and potential for abuse than clinical care, and thus protections and oversight are required for research, but not for care. The research oversight system established by these regulations has been effective, with most clinical research reviewed in advance for possible risk and burdens and for threats to autonomy and justice. For clinical research, however, it has become too much of a one-size-fits-all mechanism. As more comparative effectiveness and other research on widely used clinical interventions are conducted, research oversight should be fit for purpose for these kinds of trials, with the degree of oversight based on 2 morally relevant features of a trial. The first of these features is the degree to which risks and burdens increase or change when research is integrated into clinical care compared with what patient-participants would have experienced in care absent the research. The second is whether the activity restricts meaningful patient decision-making about care in morally important ways: (1) does the research restrict a choice or decision that patients ordinarily are or should be involved in and (2) does research participation remove from patients the ability to make a decision that may be meaningful to them, one based, at least in part, on their values, priorities, logistical or practical considerations, and the like? Whether clinical trials add risk or burden to what patients would otherwise have experienced, and whether studies restrict meaningful decisions patients would or should have had the opportunity to make, should help to determine whether clinical studies are designated as greater than vs minimal risk. Further, it is recommended that investigators and oversight bodies consider streamlined consent procedures for research presenting minimal additional risk or burden and that does not constrain meaningful patient decisions, rather than assuming that waiving all consent requirements is the only alternative.

Conclusions and relevance: Ethical oversight of clinical research must be fit for purpose-with greater oversight for studies with greater risks, uncertainties, and impacts on meaningful patient decisions-and more streamlined oversight for other types of research.

The ethical challenges raised in the design and conduct of pragmatic trials: an interview study with key stakeholders (Source) 

Background: There is a concern that the apparent effectiveness of interventions tested in clinical trials may not be an accurate reflection of their actual effectiveness in usual practice. Pragmatic randomized controlled trials (RCTs) are designed with the intent of addressing this discrepancy. While pragmatic RCTs may increase the relevance of research findings to practice they may also raise new ethical concerns (even while reducing others). To explore this question, we interviewed key stakeholders with the aim of identifying potential ethical challenges in the design and conduct of pragmatic RCTs with a view to developing future guidance on these issues.

Methods: Interviews were conducted with clinical investigators, methodologists, patient partners, ethicists, and other knowledge users (e.g., regulators). Interviews covered experiences with pragmatic RCTs, ethical issues relevant to pragmatic RCTs, and perspectives on the appropriate oversight of pragmatic RCTs. Interviews were coded inductively by two coders. Interim and final analyses were presented to the broader team for comment and discussion before the analytic framework was finalized.

Results: We conducted 45 interviews between April and September 2018. Interviewees represented a range of disciplines and jurisdictions as well as varying content expertise. Issues of importance in pragmatic RCTs were (1) identification of relevant risks from trial participation and determination of what constitutes minimal risk; (2) determining when alterations to traditional informed consent approaches are appropriate; (3) the distinction between research, quality improvement, and practice; (4) the potential for broader populations to be affected by the trial and what protections they might be owed; (5) the broader range of trial stakeholders in pragmatic RCTs, and determining their roles and responsibilities; and (6) determining what constitutes "usual care" and implications for trial reporting.

Conclusions: Our findings suggest both the need to discuss familiar ethical topics in new ways and that there are new ethical issues in pragmatic RCTs that need greater attention. Addressing the highlighted issues and developing guidance will require multidisciplinary input, including patient and community members, within a broader and more comprehensive analysis that extends beyond consent and attends to the identified considerations relating to risk and stakeholder roles and responsibilities.

Tri­-Council Policy Statement: Ethical Conduct for Research Involving Humans (Source) 

The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS 2, 2022) is Canada’s national framework for ensuring that all research involving human participants, data, or biological materials is conducted ethically. Jointly issued by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Social Sciences and Humanities Research Council (SSHRC), it establishes the principles of Respect for Persons, Concern for Welfare, and Justice as the foundation for ethical decision-making in research. The policy outlines requirements for informed consent, privacy and confidentiality, fairness and inclusion, Indigenous engagement, and Research Ethics Board (REB) oversight, while also addressing specialized contexts such as clinical trials, qualitative studies, and genetic or biological material research. Compliance with TCPS 2 is mandatory for any research funded by the Tri-Council agencies and serves as the ethical benchmark for all human research in Canada.