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Register a new userConditional separable effects
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Mats Julius Stensrud
Publication date
2020
fields
Mathematical Statistics
and research's language is
English
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Researchers are often interested in treatment effects on outcomes that are only defined conditional on a post-treatment event status. For example, in a study of the effect of different cancer treatments on quality of life at end of follow-up, the quality of life of individuals who die during the study is undefined. In these settings, a naive contrast of outcomes conditional on the post-treatment variable is not an average causal effect, even in a randomized experiment. Therefore the effect in the principal stratum of those who would have the same value of the post-treatment variable regardless of treatment, such as the always survivors in a truncation by death setting, is often advocated for causal inference. While this principal stratum effect is a well defined causal contrast, it is often hard to justify that it is relevant to scientists, patients or policy makers, and it cannot be identified without relying on unfalsifiable assumptions. Here we formulate alternative estimands, the conditional separable effects, that have a natural causal interpretation under assumptions that can be falsified in a randomized experiment. We provide identification results and introduce different estimators, including a doubly robust estimator derived from the nonparametric influence function. As an illustration, we estimate a conditional separable effect of chemotherapies on quality of life in patients with prostate cancer, using data from a randomized clinical trial.
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In competing event settings, a counterfactual contrast of cause-specific cumulative incidences quantifies the total causal effect of a treatment on the event of interest. However, effects of treatment on the competing event may indirectly contribute to this total effect, complicating its interpretation. We previously proposed the separable effects (Stensrud et al, 2019) to define direct and indirect effects of the treatment on the event of interest. This definition presupposes a treatment decomposition into two components acting along two separate causal pathways, one exclusively outside of the competing event and the other exclusively through it. Unlike previous definitions of direct and indirect effects, the separable effects can be subject to empirical scrutiny in a study where separate interventions on the treatment components are available. Here we extend and generalize the notion of the separable effects in several ways, allowing for interpretation, identification and estimation under considerably weaker assumptions. We propose and discuss a definition of separable effects that is applicable to general time-varying structures, where the separable effects can still be meaningfully interpreted, even when they cannot be regarded as direct and indirect effects. We further derive weaker conditions for identification of separable effects in observational studies where decomposed treatments are not yet available; in particular, these conditions allow for time-varying common causes of the event of interest, the competing events and loss to follow-up. For these general settings, we propose semi-parametric weighted estimators that are straightforward to implement. As an illustration, we apply the estimators to study the separable effects of intensive blood pressure therapy on acute kidney injury, using data from a randomized clinical trial.
We propose a general new method, the conditional permutation test, for testing the conditional independence of variables $X$ and $Y$ given a potentially high-dimensional random vector $Z$ that may contain confounding factors. The proposed test permutes entries of $X$ non-uniformly, so as to respect the existing dependence between $X$ and $Z$ and thus account for the presence of these confounders. Like the conditional randomization test of Cand`es et al. (2018), our test relies on the availability of an approximation to the distribution of $X mid Z$. While Cand`es et al. (2018)s test uses this estimate to draw new $X$ values, for our test we use this approximation to design an appropriate non-uniform distribution on permutations of the $X$ values already seen in the true data. We provide an efficient Markov Chain Monte Carlo sampler for the implementation of our method, and establish bounds on the Type I error in terms of the error in the approximation of the conditional distribution of $Xmid Z$, finding that, for the worst case test statistic, the inflation in Type I error of the conditional permutation test is no larger than that of the conditional randomization test. We validate these theoretical results with experiments on simulated data and on the Capital Bikeshare data set.
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