Bayesian survival analysis with nonproportional hazards: Metanalysis of combination pravastatin-aspirin
Bayesian survival analysis with nonproportional hazards: Metanalysis of combination pravastatin-aspirin
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DOI：
10.1198/016214504000000052
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发表时间：
2004-03-01
影响因子：
3.7
通讯作者：
Belder, R
中科院分区：
文献类型：
--
作者：
Berry, SM;Berry, DA;Belder, R
普伐他汀和阿司匹林均已获得美国食品和药物管理局 (FDA) 批准用于心血管事件的二级预防。本文描述了成功提交给 FDA 的统计分析，该分析认为共同包装普伐他汀和阿司匹林可提供健康益处。从功效的角度来看，这意味着联合用药比单独考虑任何一种药物更有效。我们提出了三种贝叶斯分层生存模型，并将其应用于五项随机临床试验的结果。这些试验评估了普伐他汀在二级预防中的益处。这些试验中记录了患者阿司匹林的使用情况。但阿司匹林的分配不是随机的。我们比较了普伐他汀和阿司匹林联合用药和单独用药的效果。我们关注心肌梗死发生时间，尽管这只是向 FDA 提交的报告中考虑的几个终点之一。其中两个模型假设了比例风险，而第三个则没有。在所有三个模型中，我们都根据已知的协变量进行调整。我们的主要关注点是普伐他汀和阿司匹林的组合至少与单独考虑的药物一样有效的可能性。我们还发现组合具有协同效应的概率，即组合的效果优于两种药物单独效果的总和。
Both pravastatin and aspirin are approved by the U.S. Food and Drug Administration (FDA) for secondary prevention of cardiovascular events. This article describes statistical analyses used for a successful submission to the FDA that contends that copackaging pravastatin and aspirin provides a health benefit. From the efficacy perspective this is taken to mean that the combination is more effective than either agent considered alone. We present three Bayesian hierarchical survival models and apply them to the results of five randomized clinical trials. These trials evaluated the benefit of pravastatin in the secondary-prevention setting. Aspirin use was recorded for patients in these trials. but assignment to aspirin was not randomized. We compare the effects of pravastatin and aspirin considered in combination and when given alone. We focus on time to myocardial infarction, although it was just one of several endpoints considered in the presentation to the FDA. Two of the models assume proportional hazards and the third does not. In all three models we adjust for known covariates. Our principal focus is the probability that the combination of pravastatin and aspirin is at least as effective as the agents considered separately. We also find the probability that the combination is synergistic in the sense that the effect of the combination is better than the sum of the effects of the two agents taken alone.