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Table 3 Key ethical questions for future evaluation

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

Key feature of pragmatic trialsExplanationEthical questions to be addressed
A key feature of pragmatic RCTs is that they often involve minimal modification of the clinical setting or organization and evaluate interventions commonly used in practicePragmatic trials may include elements of clinical practice, quality improvement, and research and these may have different implications for regulation or oversightWhat are the ethically important distinctions between research, clinical practice and quality improvement in pragmatic trials? What criteria should be used to determine the type of oversight and regulation necessary for a pragmatic RCTs? How should these activities be regulated and on what basis would regulatory oversight differ?
Pragmatic RCTs seek to minimize the discrepancy between the trial and usual clinical care, which may include approaches to patient consentPragmatic RCTs may seek to recruit participants using altered consent approaches compared to standard written consent for research.When are alterations and waivers of traditional informed consent appropriate in pragmatic RCTs? Does the general requirement for larger sample sizes and emphasis on external validity in pragmatic RCTs constitute a sufficient justification for waivers or alterations of consent (or may it raise concerns)?
It can be difficult to determine which risks and benefits need to be disclosed to participants in the informed consent process when risks may be no more than usual careWhat risks and benefits should be disclosed to participants in pragmatic RCTs of usual care interventions?
A key feature of pragmatic RCTs is that they seek to generate evidence applicable to a (the) wider populationThere may be different actors (both within and outside of the trial in question) whose interests are affected by pragmatic RCTs in morally relevant waysWho are the individuals or groups affected by the trial (and how do we determine who have legitimate claims on those conducting the trial)?
Systemic barriers to trial participation may exist even when individuals are eligibleWhat are the responsibilities of identified stakeholders with respect to equity of access to pragmatic RCTs for those who are eligible? How should these responsibilities be determined?
A key feature of pragmatic RCTs is that they often include policy-relevant or health systems-relevant questionsThere may be stakeholders who may influence the conduct or outcomes in pragmatic RCTs; they may have different responsibilitiesWho are the stakeholders who have roles or responsibilities in relation to the trial (and how do we determine the individuals or groups who have roles)? What are their duties or responsibilities within the trial?
A key feature of pragmatic RCTs is that they may include a broader patient population with a broader range of risks/benefits and often assess interventions commonly used in practice (or already approved) that may be low riskDue to inclusion of heterogeneous populations, pragmatic RCTs may include risks and benefits of differing magnitude which may accrue to different individuals or groupsHow should we identify relevant risks and benefits to individuals or groups within a pragmatic RCT? How should these risks and benefits be evaluated?
Pragmatic RCTs may not be exposing participants to treatments of unproven effectiveness; the use of existing treatments may have more well-characterized risk and benefit profilesa.What criteria should be used to classify a pragmatic RCT as minimal risk?
External validity is key to pragmatic RCTs; in addition, they often include a comparator arm of “usual care” that is heterogenousIt can be difficult to determine what constitutes usual care and what meets legal definitions of accepted medical practice in pragmatic RCTsWhat evidence is required to substantiate a claim that an intervention or comparator is usual care and if this would constitute minimal risk? Are two standardized arms within a usual care range actually usual care?
Interpretation of a pragmatic RCT requires that the trial context (including the nature and variation within the intervention and comparator) is reported wellWhat are the essential elements of pragmatic RCTs that must be reported? How well are pragmatic RCTs reported, especially in relation to the constitution of usual care arms?
  1. RCT randomized controlled trial
  2. aThis may not be the case for complex interventions, which may add further difficulty for risk assessment and evaluation for risk/benefit ratios