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Abstract:
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Arming the immune system against cancer has emerged as a powerful tool in oncology during recent years. Instead of poisoning a tumor or destroying it with radiation, therapeutic cancer vaccine, a typical type of cancer immunotherapy, unleashes the immune system to combat cancer. This indirect mechanism-of-action poses the possibility of a delayed onset of clinical effect, which results in a delayed separation of survival curves between treatment and placebo groups in therapeutic cancer vaccine trials with time-to-event endpoints. This violates the proportional hazard assumption. As a result, the conventional study design based on the regular log-rank test ignoring the delay effect would lead to a loss of power. In this paper, we propose two innovative approaches for sample size and power calculation using piecewise-weighted log-rank test to properly incorporate the delayed effect into the study design. Both theoretical derivations and empirical studies demonstrate that the proposed methods, accounting for the delayed effect, can reduce sample size dramatically while achieving the target power relative to the standard practice.
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