Choice of time-scale in Cox's model analysis of epidemiologic cohort data:: a simulation study
Choice of time-scale in Cox's model analysis of epidemiologic cohort data:: a simulation study
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DOI：
10.1002/sim.2098
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发表时间：
2004-12-30
影响因子：
2
通讯作者：
Bénichou, J
中科院分区：
文献类型：
--
作者：
Thiébaut, ACM;Bénichou, J
考克斯回归模型广泛用于流行病学队列研究中评估潜在危险因素与疾病发生之间的关联。虽然年龄通常是疾病风险的一个强有力的决定因素，但作者经常使用研究时间而不是年龄作为时间尺度，就像临床试验一样。除非基线风险是年龄的指数函数，否则这种方法可能会产生与使用年龄作为时间尺度不同的相对风险估计值，即使在调整年龄时也是如此。我们进行了一项模拟研究，以调查年龄和协变量之间不同程度的关联的偏倚的存在和程度。从指数、Weibull或分段Weibull分布生成疾病发作的年龄，并考虑固定和时间依赖性二分协变量。我们没有观察到使用年龄作为时间尺度的偏倚。在使用研究时间后，我们验证了指数分布的年龄与疾病发作之间不存在偏倚。对于非指数分布，我们发现，即使协变量与年龄无关，也可能发生偏倚。在与年龄显著相关的情况下，特别是与时间依赖性协变量相关的情况下，可能为重度。这些研究结果说明了一个队列的84329名法国妇女前瞻性乳腺癌的发生。鉴于我们的结果，我们强烈建议不要使用研究时间作为分析流行病学队列数据的时间尺度。版权所有（C）2004约翰威利父子有限公司。
Cox's regression model is widely used for assessing associations between potential risk factors and disease occurrence in epidemiologic cohort studies. Although age is often a strong determinant of disease risk, authors have frequently used time-on-study instead of age as the time-scale, as for clinical trials. Unless the baseline hazard is an exponential function of age, this approach can yield different estimates of relative hazards than using age as the time-scale, even when age is adjusted for. We performed a simulation study in order to investigate the existence and magnitude of bias for different degrees of association between age and the covariate of interest. Age to disease onset was generated from exponential, Weibull or piecewise Weibull distributions, and both fixed and time-dependent dichotomous covariates were considered. We observed no bias upon using age as the time-scale. Upon using time-on-study, we verified the absence of bias for exponentially distributed age to disease onset. For non-exponential distributions, we found that bias could occur even when the covariate of interest was independent from age. It could be severe in case of substantial association with age, especially with time-dependent covariates. These findings were illustrated on data from a cohort of 84 329 French women followed prospectively for breast cancer occurrence. In view of our results, we strongly recommend not using time-on-study as the time-scale for analysing epidemiologic cohort data. Copyright (C) 2004 John Wiley Sons, Ltd.