Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. With the emergence of immunotherapy and novel targeted therapies, departure from the proportional hazard assumption is not rare in nowadays clinical research. Under non-proportional hazards, the hazard ratio does not have a straightforward clinical interpretation, and the log-rank test is no longer the most powerful statistical test even though it is still valid. Nevertheless, the log-rank test and the hazard ratio are still the primary analysis tools, and traditional approaches such as sample size increase are still proposed to account for the impact of non-proportional hazards. The weighed log-rank test and the test based on the restricted mean survival time (RMST) are receiving a lot of attention as a potential alternative to the log-rank test. We conduct a simulation study comparing the performance and operating characteristics of the log-rank test, the weighted log-rank test and the test based on the RMST, including a treatment effect estimation, under different non-proportional hazards patterns. Results show that, under non-proportional hazards, the hazard ratio and weighted hazard ratio have no straightforward clinical interpretation whereas the RMST ratio can be interpreted regardless of the proportional hazards assumption. In terms of power, the RMST achieves a similar performance when compared to the log-rank test.

比例风险是设计肿瘤学验证性临床试验时的常见假设。随着免疫疗法和新型靶向疗法的出现，当今临床研究中偏离比例风险假设的情况并不罕见。在非比例风险下，风险比没有直接的临床解释，对数秩检验不再是最有力的统计检验，尽管它仍然有效。尽管如此，对数秩检验和风险比仍然是主要的分析工具，并且仍然提出增加样本量等传统方法来解释非比例风险的影响。加权对数秩检验和基于受限平均生存时间 (RMST) 的检验作为对数秩检验的潜在替代方案而受到广泛关注。我们进行了一项模拟研究，比较了对数秩检验、加权对数秩检验和基于 RMST 的检验（包括不同非比例风险模式下的治疗效果估计）的性能和操作特征。结果表明，在非比例风险下，风险比和加权风险比没有直接的临床解释，而无论比例风险假设如何，都可以解释 RMST 比。就功效而言，RMST 与对数秩测试相比取得了相似的性能。