Gregory E. Simon | Searcharxiv

arXiv2024

Assessing treatment effects in observational data with missing confounders: A comparative study of practical doubly-robust and traditional missing data methods

In pharmacoepidemiology, safety and effectiveness are frequently evaluated using readily available administrative and electronic health records data. In these settings, detailed confounder data are often not available in all data sources and therefore missing on a subset of individuals. Multiple imputation (MI) and inverse-probability weighting (IPW) are go-to analytical methods to handle missing data and are dominant in the biomedical literature. Doubly-robust methods, which are consistent under fewer assumptions, can be more efficient with respect to mean-squared error. We discuss two practical-to-implement doubly-robust estimators, generalized raking and inverse probability-weighted targeted maximum likelihood estimation (TMLE), which are both currently under-utilized in biomedical studies. We compare their performance to IPW and MI in a detailed numerical study for a variety of synthetic data-generating and missingness scenarios, including scenarios with rare outcomes and a high missingness proportion. Further, we consider plasmode simulation studies that emulate the complex data structure of a large electronic health records cohort in order to compare anti-depressant therapies in a rare-outcome setting where a key confounder is prone to more than 50\% missingness. We provide guidance on selecting a missing data analysis approach, based on which methods excelled with respect to the bias-variance trade-off across the different scenarios studied.

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arXiv2023

Inference on summaries of a model-agnostic longitudinal variable importance trajectory with application to suicide prevention

Risk of suicide attempt varies over time. Understanding the importance of risk factors measured at a mental health visit can help clinicians evaluate future risk and provide appropriate care during the visit. In prediction settings where data are collected over time, such as in mental health care, it is often of interest to understand both the importance of variables for predicting the response at each time point and the importance summarized over the time series. Building on recent advances in estimation and inference for variable importance measures, we define summaries of variable importance trajectories and corresponding estimators. The same approaches for inference can be applied to these measures regardless of the choice of the algorithm(s) used to estimate the prediction function. We propose a nonparametric efficient estimation and inference procedure as well as a null hypothesis testing procedure that are valid even when complex machine learning tools are used for prediction. Through simulations, we demonstrate that our proposed procedures have good operating characteristics. We use these approaches to analyze electronic health records data from two large health systems to investigate the longitudinal importance of risk factors for suicide attempt to inform future suicide prevention research and clinical workflow.

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