Data-Adaptive Identification of Effect Modifiers through Stochastic Shift Interventions and Cross-Validated Targeted Learning

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Main Authors: McCoy, David, Zhang, Wenxin, Hubbard, Alan, van der Laan, Mark, Schuler, Alejandro
Format: Preprint
Published: 2024
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_version_ 1866909422801911808
author McCoy, David
Zhang, Wenxin
Hubbard, Alan
van der Laan, Mark
Schuler, Alejandro
author_facet McCoy, David
Zhang, Wenxin
Hubbard, Alan
van der Laan, Mark
Schuler, Alejandro
contents In epidemiology, identifying subpopulations that are particularly vulnerable to exposures and those who may benefit differently from exposure-reducing interventions is essential. Factors such as age, gender-specific vulnerabilities, and physiological states such as pregnancy are critical for policymakers when setting regulatory guidelines. However, current semi-parametric methods for estimating heterogeneous treatment effects are often limited to binary exposures and can function as black boxes, lacking clear, interpretable rules for subpopulation-specific policy interventions. This study introduces a novel method that uses cross-validated targeted minimum loss-based estimation (TMLE) paired with a data-adaptive target parameter strategy to identify subpopulations with the most significant differential impact of simulated policy interventions that reduce exposure. Our approach is assumption-lean, allowing for the integration of machine learning while still yielding valid confidence intervals. We demonstrate the robustness of our methodology through simulations and application to data from the National Health and Nutrition Examination Survey. Our analysis of NHANES data on persistent organic pollutants (POPs) and leukocyte telomere length (LTL) identified age as a significant effect modifier. Specifically, we found that exposure to 3,3',4,4',5-pentachlorobiphenyl (PCNB) consistently had a differential impact on LTL, with a one-standard deviation reduction in exposure leading to a more pronounced increase in LTL among younger populations compared to older ones. We offer our method as an open-source software package, EffectXshift, enabling researchers to investigate the effect modification of continuous exposures. The EffectXshift package provides clear and interpretable results, informing targeted public health interventions and policy decisions.
format Preprint
id arxiv_https___arxiv_org_abs_2406_10792
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Data-Adaptive Identification of Effect Modifiers through Stochastic Shift Interventions and Cross-Validated Targeted Learning
McCoy, David
Zhang, Wenxin
Hubbard, Alan
van der Laan, Mark
Schuler, Alejandro
Methodology
In epidemiology, identifying subpopulations that are particularly vulnerable to exposures and those who may benefit differently from exposure-reducing interventions is essential. Factors such as age, gender-specific vulnerabilities, and physiological states such as pregnancy are critical for policymakers when setting regulatory guidelines. However, current semi-parametric methods for estimating heterogeneous treatment effects are often limited to binary exposures and can function as black boxes, lacking clear, interpretable rules for subpopulation-specific policy interventions. This study introduces a novel method that uses cross-validated targeted minimum loss-based estimation (TMLE) paired with a data-adaptive target parameter strategy to identify subpopulations with the most significant differential impact of simulated policy interventions that reduce exposure. Our approach is assumption-lean, allowing for the integration of machine learning while still yielding valid confidence intervals. We demonstrate the robustness of our methodology through simulations and application to data from the National Health and Nutrition Examination Survey. Our analysis of NHANES data on persistent organic pollutants (POPs) and leukocyte telomere length (LTL) identified age as a significant effect modifier. Specifically, we found that exposure to 3,3',4,4',5-pentachlorobiphenyl (PCNB) consistently had a differential impact on LTL, with a one-standard deviation reduction in exposure leading to a more pronounced increase in LTL among younger populations compared to older ones. We offer our method as an open-source software package, EffectXshift, enabling researchers to investigate the effect modification of continuous exposures. The EffectXshift package provides clear and interpretable results, informing targeted public health interventions and policy decisions.
title Data-Adaptive Identification of Effect Modifiers through Stochastic Shift Interventions and Cross-Validated Targeted Learning
topic Methodology
url https://arxiv.org/abs/2406.10792