A Bayesian-adaptive decision-theoretic approach can reduce the sample sizes for multiarm exercise oncology trials.

Abstract

OBJECTIVES

Adaptive designs may reduce trial sample sizes and costs. This study illustrates a Bayesian-adaptive decision-theoretic design applied to a multiarm exercise oncology trial.

STUDY DESIGN AND SETTING

In the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES) trial, 230 breast cancer patients receiving chemotherapy were randomized to supervised resistance and aerobic exercise (OnTrack), home-based physical activity (OncoMove) or usual care (UC). Data were reanalyzed as an adaptive trial using both Bayesian decision-theoretic and a frequentist group-sequential approach incorporating interim analyses after every 36 patients. Endpoint was chemotherapy treatment modifications (any vs. none). Bayesian analyses were performed for different continuation thresholds and settings with and without arm dropping and both in a 'pick-the-winner' and a 'pick-all-treatments-superior-to-control' setting.

RESULTS

Treatment modifications occurred in 34% of patients in UC and OncoMove vs. 12% in OnTrack (P = 0.002). Using a Bayesian-adaptive decision-theoretic design, OnTrack was identified as most effective after 72 patients in the 'pick-the-winner' setting and after 72-180 patients in the 'pick-all-treatments-superior-to-control' setting. In a frequentist setting, the trial would have been stopped after 180 patients, and the proportion of patients with treatment modifications was significantly lower for OnTrack than UC.

CONCLUSION

A Bayesian-adaptive decision-theoretic approach substantially reduced the sample size required for this three-arm exercise trial, especially in the 'pick-the-winner' setting.