Trial-level factors affecting accrual rate of systemic sclerosis randomized clinical trials.

Objectives: To estimate the average time to complete patient enrollment and identify factors associated with accrual rates in systemic sclerosis (SSc) randomized controlled trials (RCTs).

Methods: We searched published SSc-RCTs indexed in PubMed from 2000 to 2024, selecting those with recruitment completed before the COVID-19 pandemic. We recorded key trial features (country, phase, randomization ratio, intervention, blinding, funding source, outcome type) and enrollment year(s). We measured enrollment duration and accrual rate (participants per month). A multivariable negative binomial generalized linear model was used to identify factors associated with accrual rate.

Results: We included 80 studies, mostly single-country (75.0 %) and industry-funded (57.5 %), mainly recruiting in Europe (36.2 %) and North America (22.5 %). In 65 % of studies, both limited and diffuse SSc patients were enrolled. The median sample size was 40.5 patients, with 20 % of RCTs enrolling ≥100 patients. The median recruitment time was 15 months (IQR 9.9 - 30.0), with a median accrual rate of 3.1 (IQR 1.6 - 5.5) participants per month. Recruitment rates varied over time, with faster accrual early in the 2000s and after 2012, and a slower period in between. Multivariable analysis showed that accrual rate was positively associated with skewed randomization, blinding, non-industry funding, international recruitment, and inclusion of both SSc subsets, especially compared to studies involving only dcSSc patients.

Conclusions: Recruiting SSc patients for RCTs has been challenging, with generally slow accrual over the past 20 years and no significant improvement over time.