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Supplemental Digital Content is Available in the Text. Sham interventions in randomized clinical trials (RCTs) of physical, psychological, and self-management (PPS) therapies for pain are highly variable in design and believed to contribute to poor internal validity. However, it has not been formally tested whether the extent to which sham controls resemble the treatment under investigation consistently affects trial outcomes, such as effect sizes, differential attrition, participant expectancy, and blinding effectiveness. Placebo- or sham-controlled RCTs of PPS interventions of clinical pain populations were searched in 12 databases. The similarity of control interventions to the experimental treatment was rated across 25 features. Meta-regression analyses assessed putative links between employed control interventions, observed effect sizes in pain-related outcomes, attrition, and blinding success. The sample included 198 unique control interventions, dominated by manual therapy and chronic musculoskeletal pain research. Meta-analyses indicated small-to-moderate benefits of active treatments over control interventions, across subgroups of manual therapies, exercise, and rehabilitation, and psychological intervention trials. Multiple meta-regression modelling demonstrated that similarity between sham control and tested interventions predicted variability in pain-related outcomes, attrition, and blinding effectiveness. Influential variables were differences relating to the extent of intervention exposure, participant experience, and treatment environments. The results support the supposed link between blinding methods and effect sizes, based on a large and systematically sourced overview of methods. However, challenges to effective blinding are complex and often difficult to discern from trial reports. Nonetheless, these insights have the potential to change trial design, conduct, and reporting and will inform guideline development. [ABSTRACT FROM AUTHOR]

Abstract: Pragmatic randomised clinical trials aim to directly inform clinical or health policy decision making. Here, we systematically review methods and design of pragmatic trials of pain therapies to examine methods, identify common challenges, and areas for improvement. Seven databases were searched for pragmatic randomised controlled clinical trials that assessed pain treatment in a clinical population of adults reporting pain. All screening steps and data extractions were performed twice. Data were synthesised descriptively, and correlation analyses between prespecified trial features and PRECIS-2 (PRagmatic-Explanatory Continuum Indicator Summary 2) ratings and attrition were performed. Protocol registration: PROSPERO-ID CRD42020178954. Of 57 included trials, only 21% assessed pharmacological interventions, the remainder physical, surgical, psychological, or self-management pain therapies. Three-quarters of the trials were comparative effectiveness designs, often conducted in multiple centres (median: 5; Q1/3: 1, 9.25) and with a median sample size of 234 patients at randomization (Q1/3: 135.5; 363.5). Although most trials recruited patients with chronic pain, reporting of pain duration was poor and not well described. Reporting was comprehensive for most general items, while often deficient for specific pragmatic aspects. Average ratings for pragmatism were highest for treatment adherence flexibility and clinical relevance of outcome measures. They were lowest for patient recruitment methods and extent of follow-up measurements and appointments. Current practice in pragmatic trials of pain treatments can be improved in areas such as patient recruitment and reporting of methods, analysis, and interpretation of data. These improvements will facilitate translatability to other real-world settings-the purpose of pragmatic trials. [ABSTRACT FROM AUTHOR]