Defining usual care comparators when designing pragmatic trials of complex health interventions: a methodology review.

Background: Pragmatic trials evaluating complex health interventions often compare them to usual care. This comparator should resemble care as provided in everyday practice. However, usual care can differ for the same condition, between patients and practitioners, across clinical sites and over time. Heterogeneity within a usual care arm can raise methodological and ethical issues. To address these it may be necessary to standardise what usual care entails, although doing so may compromise a trial's external validity. Currently, there is no guidance detailing how researchers should decide the content of their usual care comparators. We conducted a methodology review to summarise current thinking about what should inform this decision.

Methods: MEDLINE, Embase, CINAHL and PsycINFO were searched from inception to January 2022. Articles and book chapters that discussed how to identify or develop usual care comparators were included. Experts in the field were also contacted. Reference lists and forward citation searches of included articles were screened. Data were analysed using a narrative synthesis approach.

Results: One thousand nine hundred thirty records were identified, 1611 titles and abstracts screened, 112 full texts screened, and 16 articles included in the review. Results indicated that the content of a usual care comparator should be informed by the aims of the trial, existing care practices, clinical guidelines, and characteristics of the target population. Its content should also be driven by the trial's requirements to protect participants, inform practice, and be methodologically robust, efficient, feasible and acceptable to stakeholders. When deciding the content of usual care, researchers will need to gather information about these drivers, balance tensions that might occur when responding to different trial objectives, and decide how usual care will be described and monitored in the trial.

Discussion: When deciding the content of a usual care arm, researchers need to understand the context in which a trial will be implemented and what the trial needs to achieve to address its aim and remain ethical. This is a complex decision-making process and trade-offs might need to be made. It also requires research and engagement with stakeholders, and therefore time and funding during the trial's design phase.

Trial Registration: PROSPERO CRD42022307324.