Joint modelling of longitudinal and competing risks data
Joint modelling of longitudinal and competing risks data
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DOI：
10.1002/sim.3451
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发表时间：
2008-12-30
影响因子：
2
通讯作者：
Marson, A. G.
中科院分区：
文献类型：
--
作者：
Williamson, P. R.;Kolamunnage-Dona, R.;Marson, A. G.
用于纵向和生存数据联合建模的可用方法通常对于事件结果的时间只有一种故障类型。我们扩展了该方法以允许竞争风险数据。我们拟合了一个特定原因的危害子模型，以允许竞争风险，纵向测量与每个失败原因之间存在单独的潜在关联。该方法应用于抗癫痫药物 (AED) SANAD 试验的数据，作为研究药物滴定对拉莫三嗪 (LTG) 和卡马西平 (CBZ) 对治疗失败的相对影响的影响的一种手段。有人担心差异滴定率可能对 CBZ 不利。当在联合模型中考虑到校准剂量时，LTG 对导致停药的不可接受的不良事件的有益作用并没有减弱，甚至略有增加。由于癫痫发作控制不足，调整 LTG 相对于 CBZ 的滴定率导致前者对药物戒断的影响不变。从本次分析来看，LTG 仍然是首选的 AED。版权所有 (C) 2008 约翰·威利父子有限公司
Available methods for joint modelling of longitudinal and survival data typically have only one failure type for the time to event outcome. We extend the methodology to allow for competing risks data. We fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure.The method is applied to data from the SANAD trial of anti-epileptic drugs (AEDs), as a means of investigating the effect of drug titration on the relative effects of lamotrigine (LTG) and carbamazepine (CBZ) on treatment failure. Concern had been expressed that differential titration rates may have been to the disadvantage of CBZ. The beneficial effect of LTG on unacceptable adverse events leading to drug withdrawal did not lessen and indeed increased slightly when a calibrated dose was accounted for in the joint model. Adjustment for the titration rate of LTG relative to CBZ resulted in an unchanged effect of the former on drug withdrawals due to inadequate seizure control. LTG remains the AED of choice from this analysis. Copyright (C) 2008 John Wiley & Sons, Ltd.