Borrowing Concurrent Information from Non-Concurrent Control to Enhance Statistical Efficiency in Platform Trials

Abstract

In this paper, considering time-to-event endpoints under the proportional hazard model assumption, we introduce a new concept of NCC concurrent observation time (NCC COT), and propose to borrow NCC COT through left truncation. This assumes that the NCC COT and CC are comparable. If the protocol does not prohibit NCC patients to change the standard of care while on study, NCC COT and CC likely will share the same standard of care. A simulated example is provided to demonstrate the approach. Using exponential distributions, the simulated example assumes that NCC COT and CC have the same hazard, and the treatment group has a lower hazard. The estimated HR comparing treatment to the pooled control group is 0.744 (95% CI 0.575, 0.962), whereas the comparison to the CC group alone is 0.755 (95% CI 0.566, 1.008), with corresponding p-values of 0.024 versus 0.057, respectively. This suggests that borrowing NCC COT can improve statistical efficiency when the exchangeability assumption holds. This article proposes an innovative approach of borrowing NCC COT to enhance statistical inference in platform trials under appropriate scenarios.