Evaluating the Performance of High-Dimensional Propensity Scores Compared with Standard Propensity Scores for Comparing Antihypertensive Therapies in the CPRD GOLD Database

INTRODUCTION: Propensity score (PS) matching is widely used in medical record studies to create balanced treatment groups, but relies on prior knowledge of confounding factors. High-dimensional PS (hdPS) is a semi-automated algorithm that selects variables with the highest potential for confounding from medical databases. The objective of this study was to evaluate performance of hdPS and PS when used to compare antihypertensive therapies in the UK clinical practice research datalink (CPRD) GOLD database. METHODS: Patients initiating antihypertensive treatment with either monotherapy or bitherapy were extracted from the CPRD GOLD database. Simulated datasets were generated using plasmode simulations with a marginal hazard ratio (HRm) of 1.29 for bitherapy versus monotherapy for reaching blood pressure control at 3 months. Either 16 or 36 known covariates were forced into the PS and hdPS models, and 200 additional variables were automatically selected for hdPS. Sensitivity analyses were conducted to assess the impact of removing known confounders from the database on hdPS performance. RESULTS: With 36 known covariates, the estimated HRm (RMSE) was 1.31 (0.05) for hdPS and 1.30 (0.04) for PS matching; the crude HR was 0.68 (0.61). Using 16 known covariates, the estimated HRm (RMSE) was 1.23 (0.10) and 1.09 (0.20) for hdPS and PS, respectively. Performance of hdPS was not compromised when known confounders were removed from the database. RESULTS ON REAL DATA: With 49 investigator-selected covariates, the HR was 1.18 (95% CI 1.10; 1.26) for PS and 1.33 (95% CI 1.22; 1.46) for hdPS. Both methods yielded the same conclusion, suggesting superiority of bitherapy over monotherapy for time to blood pressure control. CONCLUSION: HdPS can identify proxies for missing confounders, thereby having an advantage over PS in case of unobserved covariates. Both PS and hdPS showed superiority of bitherapy over monotherapy for reaching blood pressure control. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40119-023-00316-7.