Electronic health record (EHR) discontinuity (i.e., receiving care outside of the study EHR system), can lead to information bias in EHR-based real-world evidence (RWE) studies. An algorithm has been previously developed to identify patients with high EHR-continuity. We sought to assess whether applying this algorithm to patient selection for inclusion can reduce bias caused by data-discontinuity in four RWE examples. Among Medicare beneficiaries aged >=65 years from 2007 to 2014, we established 4 cohorts assessing drug effects on short-term or long-term outcomes, respectively. We linked claims data with two US EHR systems and calculated %bias of the multivariable-adjusted effect estimates based on only EHR vs. linked EHR-claims data because the linked data capture medical information recorded outside of the study EHR. Our study cohort included 77,288 patients in system 1 and 60,309 in system 2. We found the subcohort in the lowest quartile of EHR-continuity captured 72-81% of the short-term and only 21-31% of the long-term outcome events, leading to %bias of 6-99% for the short-term and 62-112% for the long-term outcome examples. This trend appeared to be more pronounced in the example using a nonuser comparison rather than an active comparison. We did not find significant treatment effect heterogeneity by EHR-continuity for most subgroups across empirical examples. In EHR-based RWE studies, investigators may consider excluding patients with low algorithm-predicted EHR-continuity as the EHR data capture relatively few of their actual outcomes, and treatment effect estimates in these patients may be unreliable.
© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.