How pragmatic are sarcopenia intervention studies? A systematic review

Background: Sarcopenia is an age-related<br/>muscle disease often accompanied by comorbidities, mobility issues and cognitive<br/>decline, which can limit treatment adherence in older adults. Owing to the reversible nature of sarcopenia, there has been a<br/>growing number of randomized controlled trials conducted in recent years. Yet, many randomized controlled trials (RCTs) are<br/>conducted under ideal conditions (explanatory trials), limiting their real-world<br/>applicability. In contrast, pragmatic trials aim to<br/>better reflect the complexities of clinical practice.<br/>Objective: This study is aimed at assessing the level of pragmatism in current sarcopenia RCTs and identifying design gaps to<br/>further improve the clinical relevance and feasibility of future trials in the real world.<br/>Methods: A systematic review was conducted on MEDLINE (via Ovid), Embase and Cochrane Central Register of Controlled<br/>Trials (PRISMA guidelines; PROSPERO: CRD42024571027). Eligible studies included RCTs on sarcopenia treatment using a<br/>consensus definition and published until March 2024. The PRECIS-2<br/>tool was used to assess the level of pragmatism of these<br/>RCTs across nine standard domains (eligibility, recruitment, setting, organization, flexibility of delivery, flexibility of adherence,<br/>follow-up,<br/>primary outcome and primary analysis), with an additional ‘control’ domain. The total PRECIS-2<br/>score was calculated,<br/>and subgroup analyses were conducted by intervention type, geographical location, sample size, study duration and sarcopenia<br/>definition. A higher PRECIS-2<br/>score indicates greater trial pragmatism. The risk of bias was assessed using the Cochrane<br/>Risk of Bias 2.0 tool.<br/>Results: Of the 3985 references reviewed, 54 RCTs met the inclusion criteria. The mean PRECIS-2<br/>score across its 10 domains<br/>was 2.93 (SD 1.30), reflecting a balance of explanatory and pragmatic characteristics. Organization, recruitment and primary<br/>outcome were identified as the most pragmatic domains, whereas eligibility, adherence and follow-up<br/>were the most explanatory.<br/>Subgroup analyses revealed that geographical location and sarcopenia definitions impacted significantly the overall PRECIS-2<br/>score. More precisely, studies conducted in Asia achieved higher pragmatism scores, with significant differences in setting<br/>(p = 0.029), follow-up<br/>(p = 0.014) and control (p = 0.042) domains. Studies using Asian sarcopenia criteria (e.g., AWGS) were also<br/>more pragmatic, particularly in the eligibility (p = 0.031) and control (p = 0.005) domains.<br/>Conclusion: This systematic review reveals a persistent gap between explanatory and pragmatic designs in sarcopenia trials.<br/>Despite growing research, few studies reflect real-world<br/>conditions. Key domains like eligibility, adherence and follow-up<br/>remain<br/>overly controlled. Greater pragmatism is needed to ensure future trials yield evidence that is both robust and clinically applicable.