Stuart Nicholls

Background: Pragmatic RCTs are intended to provided results that are directly relevant to clinical or health policy decisions, with designs concordant with this aim. While their intent to more closely align research with real-world applications may address concerns regarding the disconnect between research and practice they may also raise new ethical concerns. Methods: We conducted interviews with key stakeholders (methodologists, clinical investigators, ethicists, regulators, lay members of study teams). Interviewees were identified through published articles, funding decisions, centers known to be engaged in the design or conduct of pragmatic trials, and our investigator network. Results: We conducted 45 interviews between April-September 2018, with interviewees largely from the USA (16), Canada (10), UK (10) and mainly patient partners within study teams (16), clinical investigators (10), methodologists (7) and ethicists (7). Issues that were deemed to be more relevant or enhanced in relation to the oversight of pragmatic trials were: Risk identification and what counts as minimal risk?; The distinction (and relevance) between research, quality improvement, and practice; The potential for expanded populations affected by the trial and protections owed; The broader range of stakeholders in relation to the trial and determining their roles and responsibilities; Determining and reporting interventions or comparators as usual care, and; Determining when alterations to traditional informed consent approaches are appropriate. Discussion: To date the literature is dominated by discussion of consent and the research-practice distinction. Risk evaluation in this space was felt to be an area in need of development, particularly in relation to trials of routinely used interventions and whether these constitute research. The question of whether equal obligations are owed to all individuals affected by the trial has largely not been addressed. Each of these issues have substantive implications for the oversight of pragmatic trials. Keywords: consent, clinical trials