Hazard ratios are prone to selection bias, compromising their use as causal estimands. On the other hand, the hazard difference has been shown to remain unaffected by the selection of frailty factors over time. Therefore, observed hazard differences can be used as an unbiased estimator for the causal hazard differences in the absence of confounding. However, in the presence of effect (on the hazard) heterogeneity, the hazard difference is also affected by selection. In this work, we formalize how the observed hazard difference (from a randomized controlled trial) evolves by selecting favourable levels of effect modifiers in the exposed group and thus deviates from the causal hazard difference of interest. Such selection may result in a non-linear integrated hazard difference curve even when the individual causal effects are time-invariant. Therefore, a homogeneous time-varying causal additive effect on the hazard can not be distinguished from a constant but heterogeneous causal effect. We illustrate this causal issue by studying the effect of chemotherapy on the survival time of patients suffering from carcinoma of the oropharynx using data from a clinical trial. The hazard difference can thus not be used as an appropriate measure of the causal effect without making untestable assumptions.
翻译:危险比率容易产生选择偏差,损害其作为因果估计值的使用。另一方面,危险差异被证明不会因选择脆弱因素而随着时间的推移而受到影响。因此,观察到的危险差异可以在没有混乱的情况下作为因果关系差异的公正估计符,但是,在(危险)差异存在时,危险差异也会受到选择的影响。在这项工作中,我们确定观察到的危险差异(来自随机控制的试验)是如何演变的,方法是在暴露群体中选择出有利的效果改变者,从而偏离利益因果危险差异。这种选择可能导致非线性综合危险差异曲线,即使个别因果影响是时间变化性的。因此,对危险具有同一时间变化的因果添加效应,不能与常态的、但各异的因果效应区分开来。我们通过利用临床试验的数据研究受恶性肿瘤影响的病人的生存时间,来说明这个因果问题。因此,危险差异不能作为适当衡量因果关系的假设,而无需临床试验数据加以检验。