Abstract

The main purpose of many medical studies is to estimate the effects of a treatment or exposure on an outcome. However, it is not always possible to randomize the study participants to a particular treatment, therefore observational study designs may be used. There are major challenges with observational studies; one of which is confounding. Controlling for confounding is commonly performed by direct adjustment of measured confounders; although, sometimes this approach is suboptimal due to modeling assumptions and misspecification. Recent advances in the field of causal inference have dealt with confounding by building on classical standardization methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where new estimators were developed to overcome the limitations of the previous estimators (ie, nonparametric and parametric g-formula, inverse probability weighting, double-robust, and data-adaptive estimators). We illustrate the implementation of different methods using an empirical example from the Connors study based on intensive care medicine, and most importantly, we provide reproducible and commented code in Stata, R, and Python for researchers to adapt in their own observational study. The code can be accessed at https://github.com/migariane/Tutorial_Computational_Causal_Inference_Estimators.

Highlights

  • Often, questions that motivate studies in the health, social, and behavioral sciences are causal

  • Note that we focus on a binary outcome and treatment, “classical methods” will involve logistic regression adjustment to estimate the conditional odds ratio (OR) for the association between the treatment and the outcome

  • In contrast to classical methods, the way we adjust for confounding based on the generalization of standardization (g-formula) is more coherent as we assume that the effect of right heart catheterization (RHC) on short-term mortality can differ by sex

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Summary

INTRODUCTION

Questions that motivate studies in the health, social, and behavioral sciences are causal. Rapid ongoing advances in the field of causal inference have resulted in several algorithms that improve upon classical methods (ie, outcome regression adjustment) to estimate the causal effect of a treatment on an outcome. These methods incorporate estimators using propensity scores, g-computation, or a combination of both (ie, double-robust estimators). Double-robust estimators are preferred over classical single-robust regression approaches when the research question is causal.[4,5] In this tutorial, we introduce the estimators mentioned above and show their computational implementation in regards to their chronological development (ie, the methods were developed to address the limitations of the previous approaches).

SETTING TO ESTIMATE THE ATE
Nonparametric g-formula
Method
Statistical inference
Parametric g-formula
Inverse probability weighting based on the propensity score
Marginal structural model with stabilized weights
Inverse probability weighting plus regression adjustment
Augmented inverse probability of treatment weighting
DATA-ADAPTIVE ESTIMATION
Statistical inference for data-adaptive estimators
SIMULATION
CONCLUSION
Findings
Methods
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