The progression-free survival ratio (PFSr) is a widely used measure in personalized oncology trials. It evaluates the effectiveness of treatment by comparing two consecutive event times - one under standard therapy and one under an experimental treatment. However, most proposed tests based on the PFSr cannot control the nominal type I error rate, even under mild assumptions such as random right-censoring. Consequently the results of these tests are often unreliable. As a remedy, we propose to estimate the relevant probabilities related to the PFSr by adapting recently developed methodology for the relative treatment effect between paired event times. As an additional alternative, we develop inference procedures based on differences and ratios of restricted mean survival times. An extensive simulation study confirms that the proposed novel methodology provides reliable inference, whereas previously proposed techniques break down in many realistic settings. The utility of our methods is further illustrated through an analysis of real data from a molecularly aided tumor trial.

翻译：无进展生存期比值（PFSr）是个体化肿瘤试验中广泛使用的度量指标。它通过比较标准疗法与实验性治疗下连续发生的两个事件时间来评估治疗效果。然而，基于PFSr的大多数现有检验方法即使在随机右删失等温和假设下，也无法控制名义上的第一类错误率，导致这些检验结果往往不可靠。为此，我们通过改进近期发展的配对事件时间相对治疗效果方法，提出估计与PFSr相关的关键概率。作为补充方案，我们还开发了基于限制平均生存时间差值比与比值比的推断程序。大量模拟研究证实，所提出的新方法能提供可靠的统计推断，而先前技术在许多现实场景中均失效。通过对分子辅助肿瘤试验真实数据的分析，进一步验证了本方法的实用性。