AUTHOR=Guo Yuchen , Strauss Victoria Y. , Català Martí , Jödicke Annika M. , Khalid Sara , Prieto-Alhambra Daniel TITLE=Machine learning methods for propensity and disease risk score estimation in high-dimensional data: a plasmode simulation and real-world data cohort analysis JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1395707 DOI=10.3389/fphar.2024.1395707 ISSN=1663-9812 ABSTRACT=Introduction

Machine learning (ML) methods are promising and scalable alternatives for propensity score (PS) estimation, but their comparative performance in disease risk score (DRS) estimation remains unexplored.

Methods

We used real-world data comparing antihypertensive users to non-users with 69 negative control outcomes, and plasmode simulations to study the performance of ML methods in PS and DRS estimation. We conducted a cohort study using UK primary care records. Further, we conducted a plasmode simulation with synthetic treatment and outcome mimicking empirical data distributions. We compared four PS and DRS estimation methods: 1. Reference: Logistic regression including clinically chosen confounders. 2. Logistic regression with L1 regularisation (LASSO). 3. Multi-layer perceptron (MLP). 4. Extreme Gradient Boosting (XgBoost). Covariate balance, coverage of the null effect of negative control outcomes (real-world data) and bias based on the absolute difference between observed and true effects (for plasmode) were estimated. 632,201 antihypertensive users and nonusers were included.

Results

ML methods outperformed the reference method for PS estimation in some scenarios, both in terms of covariate balance and coverage/bias. Specifically, XgBoost achieved the best performance. DRS-based methods performed worse than PS in all tested scenarios.

Discussion

We found that ML methods could be reliable alternatives for PS estimation. ML-based DRS methods performed worse than PS ones, likely given the rarity of outcomes.