Follow up after sample size re-estimation in a breast cancer trial for time to recurrence

Abstract

In an international trial of premenopausal women with hormone receptor positive operable breast cancer that compares how the timing of surgical oophorectomy and mastectomy affects time to recurrence, we re-evaluated the required sample size near the end of the planned accrual period. We had anticipated that failure probabilities used at the design stage were too high resulting in a loss of power for the hazard ratio of interest. Extending follow up to obtain the number of events expected during the initial planning was not a viable option due to evidence in several previous trials of converging hazard functions. We proceeded to develop a method to re-estimate sample size in this time to event trial based on the blinded trial. Blinded re-estimation was our preference since we did not want to risk the perception that the sample size was manipulated because a smaller effect, than was anticipated, was found. Using data from a previous trial in a similar patient population receiving the same therapy (but who were not randomized to surgery timing) and the current blinded trial data, we re-estimated the required sample size. The distribution of bootstrap re-estimates of sample size indicated no increase in sample size was needed for the proposed HR. Follow-up for this trial is now complete. We will examine the final failure rates and hazard functions to see how well our re-estimation procedure performed. We will be able to explore if the hazard functions converged dramatically and what this impact would have been without this consideration.