Nam C M, Zelen M
Department of Preventive Medicine and Public Health, Yonsei University, Seoul, Korea.
Lifetime Data Anal. 2001 Mar;7(1):5-19. doi: 10.1023/a:1009609925212.
Consider a subject entered on a clinical trial in which the major endpoint is a time metric such as death or time to reach a well defined event. During the observational period the subject may experience an intermediate clinical event. The intermediate clinical event may induce a change in the survival distribution. We consider models for the one and two sample problem. The model for the one sample problem enables one to test if the occurrence of the intermediate event changed the survival distribution. This models provides a way of carrying out non-randomized clinical trial to determine if a therapy has benefit. The two sample problem considers testing if the probability distributions, with and without an intermediate event, are the same. Statistical tests are derived using a semi-Markov or a time dependent mixture model. Simulation studies are carried out to compare these new procedures with the log rank, stratified log rank and landmark tests. The new tests appear to have uniformly greater power than these competitor tests. The methods are applied to a randomized clinical trial carried out by the Aids Clinical Trial Group (ACTG) which compared low versus high doses of zidovudine (AZT).
考虑一个进入临床试验的受试者，该试验的主要终点是一个时间指标，如死亡或达到明确界定事件的时间。在观察期内，受试者可能会经历一个中间临床事件。该中间临床事件可能会导致生存分布的变化。我们考虑单样本和两样本问题的模型。单样本问题的模型使人们能够检验中间事件的发生是否改变了生存分布。该模型提供了一种进行非随机临床试验以确定一种疗法是否有益的方法。两样本问题考虑检验有中间事件和无中间事件时的概率分布是否相同。使用半马尔可夫模型或时间依赖混合模型推导统计检验。进行模拟研究以将这些新程序与对数秩检验、分层对数秩检验和地标检验进行比较。新检验似乎比这些竞争检验具有一致更高的功效。这些方法应用于由艾滋病临床试验组（ACTG）进行的一项随机临床试验，该试验比较了低剂量与高剂量齐多夫定（AZT）。
