A Doubly Robust Framework for Addressing Outcome-Dependent Selection Bias in Multi-Cohort EHR Studies

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Main Authors: Kundu, Ritoban, Shi, Xu, Kleinsasser, Michael, Fritsche, Lars G., Salvatore, Maxwell, Mukherjee, Bhramar
Format: Preprint
Published: 2024
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author Kundu, Ritoban
Shi, Xu
Kleinsasser, Michael
Fritsche, Lars G.
Salvatore, Maxwell
Mukherjee, Bhramar
author_facet Kundu, Ritoban
Shi, Xu
Kleinsasser, Michael
Fritsche, Lars G.
Salvatore, Maxwell
Mukherjee, Bhramar
contents Selection bias can hinder accurate estimation of association parameters in binary disease risk models using non-probability samples like electronic health records (EHRs). The issue is compounded when participants are recruited from multiple clinics/centers with varying selection mechanisms that may depend on the disease/outcome of interest. Traditional inverse-probability-weighted (IPW) methods, based on constructed parametric selection models, often struggle with misspecifications when selection mechanisms vary across cohorts. This paper introduces a new Joint Augmented Inverse Probability Weighted (JAIPW) method, which integrates individual-level data from multiple cohorts collected under potentially outcome-dependent selection mechanisms, with data from an external probability sample. JAIPW offers double robustness by incorporating a flexible auxiliary score model to address potential misspecifications in the selection models. We outline the asymptotic properties of the JAIPW estimator, and our simulations reveal that JAIPW achieves up to six times lower relative bias and five times lower root mean square error (RMSE) compared to the best performing joint IPW methods under scenarios with misspecified selection models. Applying JAIPW to the Michigan Genomics Initiative (MGI), a multi-clinic EHR-linked biobank, combined with external national probability samples, resulted in cancer-sex association estimates closely aligned with national benchmark estimates. We also analyzed the association between cancer and polygenic risk scores (PRS) in MGI to illustrate a situation where the exposure variable is not measured in the external probability sample.
format Preprint
id arxiv_https___arxiv_org_abs_2412_00228
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle A Doubly Robust Framework for Addressing Outcome-Dependent Selection Bias in Multi-Cohort EHR Studies
Kundu, Ritoban
Shi, Xu
Kleinsasser, Michael
Fritsche, Lars G.
Salvatore, Maxwell
Mukherjee, Bhramar
Methodology
Selection bias can hinder accurate estimation of association parameters in binary disease risk models using non-probability samples like electronic health records (EHRs). The issue is compounded when participants are recruited from multiple clinics/centers with varying selection mechanisms that may depend on the disease/outcome of interest. Traditional inverse-probability-weighted (IPW) methods, based on constructed parametric selection models, often struggle with misspecifications when selection mechanisms vary across cohorts. This paper introduces a new Joint Augmented Inverse Probability Weighted (JAIPW) method, which integrates individual-level data from multiple cohorts collected under potentially outcome-dependent selection mechanisms, with data from an external probability sample. JAIPW offers double robustness by incorporating a flexible auxiliary score model to address potential misspecifications in the selection models. We outline the asymptotic properties of the JAIPW estimator, and our simulations reveal that JAIPW achieves up to six times lower relative bias and five times lower root mean square error (RMSE) compared to the best performing joint IPW methods under scenarios with misspecified selection models. Applying JAIPW to the Michigan Genomics Initiative (MGI), a multi-clinic EHR-linked biobank, combined with external national probability samples, resulted in cancer-sex association estimates closely aligned with national benchmark estimates. We also analyzed the association between cancer and polygenic risk scores (PRS) in MGI to illustrate a situation where the exposure variable is not measured in the external probability sample.
title A Doubly Robust Framework for Addressing Outcome-Dependent Selection Bias in Multi-Cohort EHR Studies
topic Methodology
url https://arxiv.org/abs/2412.00228