Association of Protocol Design-Related Factors With Enrollment Duration in Clinical Trials

Abstract

Patient enrollment is a critical factor in the success of clinical trials; however, many trials fail to recruit participants within a planned timeline. Protocol design is a key barrier to efficient recruitment. However, few studies have quantitatively evaluated the association between protocol design and enrollment duration across various disease areas and time periods. We conducted a cross-sectional study using data from ClinicalTrials.gov and another related database. Industry-sponsored phase 2 and 3 drug trials completed between January 2017 and September 2024 were included. Key variables related to the protocol design were extracted from trial protocols and database entries. The enrollment duration was estimated using the trial start dates, primary completion dates, and outcome time frames. Multiple linear regression analyses were conducted to identify factors associated with enrollment duration, including comparisons between the pre- and post-COVID-19 pandemic periods. In total, 1286 trials met the inclusion criteria. Multiple linear regression identified three variables significantly associated with a longer enrollment duration: number of original enrollments (p = 0.023), number of inclusion criteria (p < 0.001), and days of assessment (p = 0.013). Before the pandemic, the number of assessment days was the primary factor, while after the pandemic, the number of inclusion criteria had the strongest association. This study demonstrated that the enrollment duration was significantly influenced by protocol design features. To improve recruitment efficiency, careful consideration of the inclusion criteria, assessment burden, and enrollment targets is essential during trial planning. Causal relationships should be interpreted cautiously and further examined in future research.