Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time models, which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the "difference" and "product" methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two methods may produce substantially different estimates in the presence of censoring or truncation, due to a form of model misspecification. Specifically, we establish that while the product method remains valid under standard assumptions in the presence of independent censoring, the difference method can be biased in the presence of such censoring whenever the error distribution of the accelerated failure time model fails to be collapsible upon marginalizing over the mediator. This will invariably be the case for most choices of mediator and outcome error distributions. A notable exception arises in case of normal mediator-normal outcome where we show consistency of both difference and product estimators in the presence of independent censoring. These results are confirmed in simulation studies and two data applications.

译文

因果中介分析的最新进展正式确定了在各种情况下估计直接和间接影响的条件。这些方法已扩展到许多生存结果模型,包括加速失效时间模型,鉴于其直观的解释,这些模型已广泛用于广泛的健康应用中。在这种情况下,有人建议在标准假设下,“差异” 和 “乘积” 方法对暴露对生存结果的间接影响产生等效估计。我们正式证明,由于某种形式的模型错误指定,在存在审查或截断的情况下,这两种方法可能会产生实质上不同的估计。具体来说,我们确定,尽管在存在独立审查的情况下,在标准假设下,乘积方法仍然有效,但在存在这种审查的情况下,只要加速失效时间模型的误差分布在中介机构上被边缘化时无法折叠,差异方法就会产生偏差。对于大多数中介和结果错误分布的选择,情况总是如此。在正常中介-正常结果的情况下,出现了一个值得注意的例外,在这种情况下,我们在存在独立审查的情况下显示了差异估计和乘积估计的一致性。这些结果在仿真研究和两个数据应用中得到了证实。

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