Evaluating the pragmatism of sarcopenia clinical trials using PRECIS-2:a systematic review

Objective: This study aims to review interventional clinical trials in sarcopenia to assess their level of pragmatism and identify gaps to improve the clinical relevance and feasibility of future trials in the real world.Methods: A systematic review was conducted using MEDLINE (via Ovid), Embase, and Cochrane Central Register of Controlled Trials (PRISMA guidelines; PROSPERO: CRD42024571027). Eligible studies included randomized controlled trials (RCTs) on sarcopenia treatment using a consensus definition. The PRECIS-2 tool was used to assess the level of pragmatism of these RCTs across nine standard domains (eligibility, recruitment, setting, organisation, flexibility of delivery, flexibility of adherence, follow-up, primary outcome, and primary analysis), with an additional "control" domain. Total PRECIS-2 scores were calculated, and subgroup analyses were conducted by intervention type, geographical location, sample size, study duration, and sarcopenia definition.Results: Of the 3,985 references reviewed, 58 RCTs met the inclusion criteria. The mean PRECIS-2 score across its 10 domains was 2.92 (SD 1.30), reflecting a balance of explanatory and pragmatic characteristics. Organisation, recruitment, and primary outcome were identified as the most pragmatic domains, whereas eligibility, adherence, and follow-up were the most explanatory. Subgroup analyses revealed that geographical location and sarcopenia definitions impacted significantly the overall PRECIS-2 score. More precisely, studies conducted in Asia achieved higher pragmatism scores, with significant differences in setting (p = 0.016), follow-up (p = 0.009), and control (p = 0.011). Studies using Asian sarcopenia criteria (e.g. AWGS) were also more pragmatic, particularly in the setting (p = 0.036) and control (p = 0.010).Conclusion: Due to the reversible nature of sarcopenia, clinical trials in this area have increased significantly in recent years. Although some methodological aspects of these RCTs follow pragmatic approaches, this systematic review highlights the need for improvements in areas such as exclusion criteria, follow-up and adherence. Specifically, there is an urgent need to design RCTs that more accurately reflect the complexity of real-world interventions in the multifaceted landscape of sarcopenia