How Pragmatic Are Sarcopenia Intervention Studies? A Systematic Review

Sarcopenia is an age-related muscle disease often accompanied by comorbidities, mobility issues and cognitive decline, which can limit treatment adherence in older adults. Owing to the reversible nature of sarcopenia, there has been a growing number of randomized controlled trials conducted in recent years. Yet, many randomized controlled trials (RCTs) are conducted under ideal conditions (explanatory trials), limiting their real-world applicability. In contrast, pragmatic trials aim to better reflect the complexities of clinical practice.

This study is aimed at assessing the level of pragmatism in current sarcopenia RCTs and identifying design gaps to further improve the clinical relevance and feasibility of future trials in the real world.

A systematic review was conducted on MEDLINE (via Ovid), Embase and Cochrane Central Register of Controlled Trials (PRISMA guidelines; PROSPERO: CRD42024571027). Eligible studies included RCTs on sarcopenia treatment using a consensus definition and published until March 2024. The PRECIS-2 tool was used to assess the level of pragmatism of these RCTs across nine standard domains (eligibility, recruitment, setting, organization, flexibility of delivery, flexibility of adherence, follow-up, primary outcome and primary analysis), with an additional 'control' domain. The total PRECIS-2 score was calculated, and subgroup analyses were conducted by intervention type, geographical location, sample size, study duration and sarcopenia definition. A higher PRECIS-2 score indicates greater trial pragmatism. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool.

Of the 3985 references reviewed, 54 RCTs met the inclusion criteria. The mean PRECIS-2 score across its 10 domains was 2.93 (SD 1.30), reflecting a balance of explanatory and pragmatic characteristics. Organization, 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 = 0.029), follow-up (p = 0.014) and control (p = 0.042) domains. Studies using Asian sarcopenia criteria (e.g., AWGS) were also more pragmatic, particularly in the eligibility (p = 0.031) and control (p = 0.005) domains.

This systematic review reveals a persistent gap between explanatory and pragmatic designs in sarcopenia trials. Despite growing research, few studies reflect real-world conditions. Key domains like eligibility, adherence and follow-up remain overly controlled. Greater pragmatism is needed to ensure future trials yield evidence that is both robust and clinically applicable.