Ethical issue | Characteristics of pragmatic RCTs raising ethical issue | Potential ethical issues for researchers and research ethics committees | |
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1. | Are activities in pragmatic RCTs research or practice? | • Commonly evaluate interventions used in routine clinical practice • Seek to evaluate interventions and assess outcomes in usual care settings • Favor unobtrusive data collection via routinely collected sources | • Difficult to clearly separate research from clinical practice • Advocates of learning health systems have challenged the research-practice distinction, but unclear if a new system will be preferable and how it satisfies current research regulations |
2. | What level of oversight is required for pragmatic RCTs? | • May involve usual care interventions or interventions posing no more than minimal risk • Address questions that directly inform decision-making by patients and healthcare providers • May have quality and service improvement as a central goal | • Current oversight procedures are time-consuming, costly, and overly complex • Some advocate that low-risk pragmatic RCTs do not require more stringent oversight than clinical practice as all patients receive an intervention used in routine clinical practice |
3. | Which study designs are appropriate in pragmatic RCTs? | • Aim to maximize representativeness; may require larger sample sizes to have adequate power • May favor novel designs, including cluster randomized, stepped wedge, registry, and cohort multiple designs | • Study designs can have differing implications for trial feasibility and logistics which must be balanced against internal and external validity • RCTs can substantially simplify trial logistics and facilitate recruitment, but ethical justification unclear • Interventions of unknown effectiveness may be rolled out to all clusters in stepped wedge trials |
4. | Who are the research participants in pragmatic RCTs? | • May involve stakeholders at multiple levels: health system; hospital; provider; patient • May evaluate interventions targeting one group, but measure outcomes on another | • Identification of research participants influences the scope of research ethics review, benefit–harm analysis, and informed consent procedures |
5. | Do patients and providers have an ethical obligation to participate in pragmatic RCTs? | • Seek to provide highly relevant evidence for patients, providers, and health systems • High degree of flexibility in intervention delivery and data collection implies low burden of study participation | • Unclear if health system leaders and providers have a prima facie ethical duty to seek to continually improve the delivery and outcomes of healthcare • Patients receive benefits from the health system which may engender an obligation to participate in research |
6. | From whom, how, and when is informed consent required in pragmatic RCTs? | • May involve usual care interventions or interventions posing no more than minimum risk • May use solely routinely collected data for outcome assessment • Informed consent can pose barriers to representative recruitment, be a burden on staff, add logistical complexity, and be costly • May expose differing groups of participants to different aspects of the research • May use cluster-level interventions that are difficult or impossible to avoid | • Unclear if simplified (“altered”) or no consent procedures are acceptable and under which conditions • Unclear what aspects of research must be disclosed to research participants • Unclear if informed consent is needed from health system leaders, decision-makers, health providers |
7. | Who are the gatekeepers in pragmatic RCTs and what are their responsibilities? | • May have an impact on group or institutional interests • May involve a variety of gatekeepers, including ministry of health, hospital administrator, and data custodians | • Lack of clarity regarding the role of gatekeepers, whose interests they protect and scope of their authority • Unclear when community consultation is appropriate |
8. | How should harm–benefit analyses be conducted in pragmatic RCTs? | • Procedures administered by a wide range of providers under imperfect conditions and in a variety of institutional settings • May evaluate policy or health delivery system interventions or usual care interventions • May use delayed implementation of intervention (stepped wedge design) | • Unclear how to determine the boundaries of appropriate provider experience and training • What constitutes usual care • Benefit–harm analysis in studies of policy or healthcare delivery is unclear • Unclear when it is appropriate to delay delivery of interventions in stepped wedge designs |
9. | How ought vulnerable groups be protected in pragmatic RCTs? | • Seek to study a representative group including individuals traditionally considered vulnerable (lower socioeconomic strata, children, pregnant women, prisoners) • Health providers/ employees may be exposed to social risks, including reputational or professional harm | • Some criticize the traditional approach to defining vulnerability and have proposed alternative definitions • Presence of vulnerable participants may be hidden • Unclear how to protect employees in pragmatic RCTs • Unclear who should set the research agenda for pragmatic RCTs |