Determinants of accrual speed in U.S. phase III therapeutic cancer clinical trials.

Abstract

e23001 Background: Patient accrual remains the dominant rate-limiting step in cancer clinical trials, driving underpowering, escalating costs, and delayed access to practice-changing therapies. Despite prior efforts, effective trial accrual strategies are limited due to a lack of generalizable, trial-level evidence to understand factors associated with accrual speed in the modern cancer clinical trial ecosystem. We sought to identify these trial-level factors associated with faster accrual speed in completed phase III adult cancer trials conducted in the U.S. Methods: We identified 517 U.S based phase III, adult, interventional therapeutic oncology trials from clinicaltrials.gov, initiated after 1/1/2000, last updated after 1/1/2010, and successfully completed before 1/1/2025. Accrual speed was defined as patients per site per month (PPSM). We conducted a trial-level case-control study, classifying trials as fast (top PPSM quintile) or slow (others) groups. We assessed temporal trends in PPSM with linear regression and compared trial characteristics between groups. Results: PPSM decreased over time (start year: β=−0.038, p=.003). Majority trials had low accrual rates while a small proportion accrued rapidly (normality test p<.001). Of the 517 trials, 104 (20%) were defined as fast accruing (mean PPSM±SD: 4.5±9.6) and 413 (80%) as slow accruing (mean PPSM±SD: 0.1±0.1). Compared with the slow group, fast-group trials were more likely to be single-site (52.9% vs 1.5%, p<.001), with small-to-medium enrollment (≤150 patients, 38.5% vs 13.6%, p<.001), primary sponsorship by non-industry institutions (65.4% vs 20.6%, p<.001), and least restrictive eligibility (lowest quintile by criteria count, 31.7% vs 19.6%, p=0.011). Accrual speed was not associated with cancer type (p=.197), and major cancer types (breast, prostate, lung, and colorectal) were not overrepresented among fast-accruing trials. Conclusions: Accrual speed in phase III cancer trials is unevenly distributed, with few fast-accruing trials and many slow-accruing trials. Fast accrual was associated with single trial site, non-industry sponsorship, smaller enrollment size, and lower eligibility restrictions. These findings support systematic evaluation of factors underlying rapid accrual to inform future trial optimization. Accrual speed (PPSM) group (n, %)　 Fast (104, 20%) Slow (413, 80%) P PPSM, mean (SD) 4.5 (9.6) 0.1 (0.1) <.001 Single-site 55 (52.9) 6 (1.5) <.001 Enrollment ≤150 40 (38.5) 56 (13.6) <.001 Randomized 95 (91.3) 381 (92.3) .918 Double/triple blind 34 (32.7) 157 (38.0) .373 Non-industry sponsored 68 (65.4) 85 (20.6) <.001 Least restrictive eligibility (lowest quintile by criteria count) 33 (31.7) 81 (19.6) .011 Cancer Type Breast 13 (12.5) 54 (13.1) 1.000 Prostate 11 (10.6) 28 (6.8) 0.270 Lung 11 (10.6) 55 (13.3) 0.559 Colorectal 3 (2.9) 21 (5.1) 0.441