Marginal hazard ratio estimates in joint frailty models for heart failure trials
Marginal hazard ratio estimates in joint frailty models for heart failure trials
复制标题
心力衰竭试验关节衰弱模型的边际风险比估计
DOI：
10.1002/bimj.201800133
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Jahn-Eimermacher
中科院分区：
文献类型：
--
作者：
Toenges;Jahn-Eimermacher
这项工作的动机是慢性心力衰竭疾病的临床试验，其中治疗对发病率（评估为复发性非致死性住院）和死亡率（评估为心血管死亡，CV死亡）均有影响。最近，针对这些疗效结局提出了联合虚弱比例风险模型，以解释住院风险率与CV死亡之间的潜在相关性。然而，更常见的临床试验结果是通过边际比例风险模型（即死亡率的考克斯模型和复发性住院的Andersen-Gill模型）得出的治疗效果估计值来呈现的。我们展示了这些边际风险比及其估计如何依赖于风险过程之间的关联，当这些风险过程实际上是由共享或依赖的脆弱性条款联系在一起时。首先，我们推导出边际风险比作为时间的函数。然后，应用最小假参数理论，我们表明，边际风险比估计住院率取决于研究持续时间和参数的基础关节脆弱模型。特别是，我们确定参数，例如治疗对死亡率的影响，确定住院的边际风险比估计值是否小于，等于或大于条件。这如何影响拒绝概率在模拟研究中进一步研究。我们的研究结果可用于解释心力衰竭试验中的边际风险比估计值，并通过CHARM-Preserved试验（其中CHARM是“坎地沙坦治疗心力衰竭降低死亡率和发病率评估”项目）的结果进行说明。
This work is motivated by clinical trials in chronic heart failure disease, where treatment has effects both on morbidity (assessed as recurrent non‐fatal hospitalisations) and on mortality (assessed as cardiovascular death, CV death). Recently, a joint frailty proportional hazards model has been proposed for these kind of efficacy outcomes to account for a potential association between the risk rates for hospital admissions and CV death. However, more often clinical trial results are presented by treatment effect estimates that have been derived from marginal proportional hazards models, that is, a Cox model for mortality and an Andersen–Gill model for recurrent hospitalisations. We show how these marginal hazard ratios and their estimates depend on the association between the risk processes, when these are actually linked by shared or dependent frailty terms. First we derive the marginal hazard ratios as a function of time. Then, applying least false parameter theory, we show that the marginal hazard ratio estimate for the hospitalisation rate depends on study duration and on parameters of the underlying joint frailty model. In particular, we identify parameters, for example the treatment effect on mortality, that determine if the marginal hazard ratio estimate for hospitalisations is smaller, equal or larger than the conditional one. How this affects rejection probabilities is further investigated in simulation studies. Our findings can be used to interpret marginal hazard ratio estimates in heart failure trials and are illustrated by the results of the CHARM‐Preserved trial (where CHARM is the ‘Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity’ programme).
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影响因子：
2.3
作者：
Putter, Hein;van Houwelingen, Hans C.
通讯作者：
van Houwelingen, Hans C.
DOI：
10.4172/2155-6180.1000191
发表时间：
2014-04
期刊：
Journal of biometrics & biostatistics
影响因子：
--
作者：
X. Liu
通讯作者：
X. Liu
影响因子：
2
作者：
Grambauer, Nadine;Schumacher, Martin;Beyersmann, Jan
通讯作者：
Beyersmann, Jan
影响因子：
1.5
作者：
Hengelbrock, Johannes;Gillhaus, Johanna;Leverkus, Friedhelm
通讯作者：
Leverkus, Friedhelm
影响因子：
1.5
作者：
Allignol, Arthur;Beyersmann, Jan;Schmoor, Claudia
通讯作者：
Schmoor, Claudia