Screening failure in systemic sclerosis randomized trials: reporting, rates, causes and trends over time

Objectives: To evaluate the completeness of reporting of pre-randomization patient' flow in SSc randomized controlled trials (RCTs) and to estimate the extent and reasons for screening failure. Methods: We searched SSc RCTs indexed in PubMed from 2000 to 2024. We recorded key trial features and checked whether they provided information on patient flow before randomization. We collected information on the adequacy of reporting of the pre-randomization phase, the number of patients screened and the extent and reasons of screening failure. Data were summarized as number (percentage) for qualitative variables and median (interquartile range) for continuous variables. Results: Of the 127 SSc RCTs retrieved, 52.9% reported patient flow before randomization, 21.2% of those published before 2011 and 65.1% of those published after. The most commonly used terms were 'screened' in 33 studies (50%) and 'assessed for eligibility' in 29 studies (44%). Of 10 043 patients screened, 5147 (51%) were considered screening failure. The median proportion of screening failures was 36% (IQR 20-58), with higher rates in studies testing non-pharmacologic interventions, lacking industry funding, lacking double-blinding or not including a placebo arm. Reasons for screening failure and their frequency were detailed for 3510 screening failure patients (68.2%). The main reasons were not meeting the eligibility criteria and patient refusal, which accounted for 72.5% and 20.8% cases, respectively. Screening failure remained stable over time. Conclusions: Reporting of screening procedures in SSc RCTs has improved over time but remains suboptimal. Most screening failures are due to patient ineligibility, followed by patient refusal, which continues to represent a significant barrier to enrolment.