Determination of hazard ratio for progression-free survival considering the tumor assessment schedule in sample size calculation.

Progression-free survival is recognized as an important endpoint in oncology clinical trials. In clinical trials aimed at new drug development, the target population often comprises patients that are refractory to standard therapy with a tumor that shows rapid progression. This situation would increase the bias of the hazard ratio calculated for progression-free survival, resulting in decreased power for such patients. Therefore, new measures are needed to prevent decreasing the power in advance when estimating the sample size. Here, I propose a novel calculation procedure to assume the hazard ratio for progression-free survival using the Cox proportional hazards model, which can be applied in sample size calculation. The hazard ratios derived by the proposed procedure were almost identical to those obtained by simulation. The hazard ratio calculated by the proposed procedure is applicable to sample size calculation and coincides with the nominal power. Methods that compensate for the lack of power due to biases in the hazard ratio are also discussed from a practical point of view.