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Alexander Levis

Publications and source records attributed to Alexander Levis.

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Local Effects of Continuous Instruments without Positivity

Instrumental variables are a popular study design for the estimation of treatment effects in the presence of unobserved confounders. In the canonical instrumental variables design, the instrument is a binary variable. In many settings, however, the instrument is continuous. Standard estimation methods can be applied with continuous instruments, but they require strong assumptions. While recent work has introduced more flexible estimation approaches, these methods require a positivity assumption that is implausible in many applications. We derive a novel family of causal estimands using stochastic dynamic interventions that allows a range of intervention distributions that are continuous with respect to the observed distribution of the instrument. These estimands focus on a specific local effect but do not require a positivity assumption. Next, we develop doubly robust estimators for these estimands that allow for estimation of the nuisance functions via nonparametric estimators. We use empirical process theory and sample splitting to derive asymptotic properties of the proposed estimators under weak conditions. In addition, we derive methods for profiling the principal strata as well as a method of sensitivity analysis. We evaluate our methods via simulation and demonstrate their feasibility using an application on the effectiveness of surgery for specific emergency conditions.

stat.ME

Comparing Causal Inference Methods for Point Exposures with Missing Confounders: A Simulation Study

Causal inference methods based on electronic health record (EHR) databases must simultaneously handle confounding and missing data. Vast scholarship exists aimed at addressing these two issues separately, but surprisingly few papers attempt to address them simultaneously. In practice, when faced with simultaneous missing data and confounding, analysts may proceed by first imputing missing data and subsequently using outcome regression or inverse-probability weighting (IPW) to address confounding. However, little is known about the theoretical performance of such $\textit{ad hoc}$ methods. In a recent paper Levis $\textit{et al.}$ outline a robust framework for tackling these problems together under certain identifying conditions, and introduce a pair of estimators for the average treatment effect (ATE), one of which is non-parametric efficient. In this work we present a series of simulations, motivated by a published EHR based study of the long-term effects of bariatric surgery on weight outcomes, to investigate these new estimators and compare them to existing $\textit{ad hoc}$ methods. While the latter perform well in certain scenarios, no single estimator is uniformly best. We conclude with recommendations for good practice in the face of partially missing confounders.

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Efficient estimation of subgroup treatment effects using multi-source data

Investigators often use multi-source data (e.g., multi-center trials, meta-analyses of randomized trials, pooled analyses of observational cohorts) to learn about the effects of interventions in subgroups of some well-defined target population. Such a target population can correspond to one of the data sources of the multi-source data or an external population in which the treatment and outcome information may not be available. We develop and evaluate methods for using multi-source data to estimate subgroup potential outcome means and treatment effects in a target population. We consider identifiability conditions and propose doubly robust estimators that, under mild conditions, are non-parametrically efficient and allow for nuisance functions to be estimated using flexible data-adaptive methods (e.g., machine learning techniques). We also show how to construct confidence intervals and simultaneous confidence bands for the estimated subgroup treatment effects. We examine the properties of the proposed estimators in simulation studies and compare performance against alternative estimators. We also conclude that our methods work well when the sample size of the target population is much larger than the sample size of the multi-source data. We illustrate the proposed methods in a meta-analysis of randomized trials for schizophrenia.

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Causal inference under transportability assumptions for conditional relative effect measures

When extending inferences from a randomized trial to a new target population, the transportability condition for conditional difference effect measures is invoked to identify the marginal causal mean difference in the target population. However, many clinical investigators believe that conditional relative effect measures are more likely to be "transportable" between populations. Here, we examine the identification and estimation of the marginal counterfactual mean difference and ratio under the transportability condition for conditional relative effect measures. We obtain identification results for two scenarios that often arise in practice when individuals in the target population (1) only have access to the control treatment, and (2) have access to the control and other treatments but not necessarily the experimental treatment evaluated in the trial. We then propose model and rate multiply robust and nonparametric efficient estimators that allow for the use of data-adaptive methods to model the nuisance functions. We examine the performance of the methods in simulation studies and illustrate their use with data from two trials of paliperidone for patients with schizophrenia. We conclude that the proposed methods are attractive when background knowledge suggests that the transportability condition for conditional relative effect measures is more plausible than alternative conditions.

stat.ME