Adaptive design increased success but does not significantly accelerate confirmatory oncology trials

초록

Background Adaptive designs (ADs) are increasingly employed to improve trial efficiency; however, their benefits over fixed designs in late-phase oncology trials remain underexplored. We aimed to determine whether ADs in phase III cancer trials are associated with primary completion time and primary endpoint success compared with fixed designs. Methods This cross-sectional study analyzed phase III randomized lung and breast cancer trials initiated between 2000 and 2020 using Aggregate Analysis of ClinicalTrials.gov database (static version downloaded April 15, 2025). Eligible trials had time-to-event primary endpoints and were completed or terminated. Trials were classified as adaptive or non-adaptive based on pre-planned design modifications. Associations between trial design and primary completion time were examined using Kaplan–Meier curves and multivariable cause-specific Cox regression, while primary endpoint success via multivariable logistic regression. Results Of 421 eligible trials, 210 employed ADs. Adoption of ADs increased over time, with group-sequential designs being most common adaptive approach. ADs showed earlier primary completion, but no significant association was observed after multivariable adjustment. Adaptive trials had higher hazards of early stopping for efficacy or futility and lower hazards of administrative termination. Among 396 trials with available results, 163 achieved primary endpoint success. Adaptive trials had higher odds of success than non-adaptive trials (66.26% vs 33.74%; odds ratio: 2.363, 95% confidence interval: 1.491 to 3.778; P<.001). Conclusion ADs were associated with higher primary endpoint success but not shorter primary completion time. Given high failure rates in late-phase oncology, ADs may improve efficiency primarily by facilitating data-driven decisions rather than accelerating trial timelines.

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