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Abstract

<jats:p>Electronic health record (EHR)-linked cohorts support association, prediction, and causal studies using longitudinally measured markers of health. However, a lab biomarker measurement is recorded only when a patient first has a medical encounter (visit process) and, a clinician orders the corresponding test and the patient follows through (observation process). These two stages may induce informative presence (IP) and informative observation (IO), respectively. Yet their drivers remain largely uncharacterized, despite evidence that understanding this recording mechanism is essential for selecting appropriate strategies for downstream analysis that treat these markers as longitudinally measured outcomes. We characterize this two-stage recording hierarchy using a stochastic recurrent-event model for the outpatient visit process and a visit-process-weighted generalized estimating equation model for biomarker recording conditional on an outpatient visit. We characterize descriptors of both processes in three EHR-linked cohorts in the US (All of Us [AoU], n=599,423; Yale New Haven Health System [YNHHS], n=319,666; Michigan Genomics Initiative [MGI], n=82,372), reporting descriptive statistics for longitudinal visits and for a panel of 68 lab biomarkers commonly measured in EHRs. We conduct detailed model-based analyses of ten biomarkers spanning multiple domains: routine monitoring, general laboratory assessment, and symptom-triggered testing. These include glucose, hemoglobin A1c [HbA1c], creatinine, hemoglobin [Hgb], white blood cell count [WBC], low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, triglycerides, C-reactive protein [CRP], and thyroid-stimulating hormone [TSH]. Across the three cohorts, the median number of outpatient visits ranged from 1.7 to 6.1 per year over a median follow-up of 4.4 to 7.2 years. Among patients with at least one recorded measurement, the median within-person proportion of visits containing a given biomarker ranged from 0.4% to 19.5%, demonstrating that more frequent visits did not necessarily translate into greater per-visit biomarker capture. In the visit-process models, chronic disease burden, and a recent history of outpatient visits were consistently associated with higher visit rates across all three cohorts whereas associations with race, ethnicity, and neighborhood-level income varied across cohorts. In per-visit observation models, the association of covariates depended on the biomarker under consideration; for example, prior cancer diagnosis was associated with more frequent measurement of blood counts but with less frequent measurement of lipids. These findings provide a deeper understanding of how to model who seeks care and what is measured as two distinct recording processes in EHR. Our empirical findings show that the descriptors of these processes vary across cohorts and biomarkers, providing guidance on how to construct these models for downstream longitudinal analyses with irregular EHR visits.</jats:p>

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Keywords

cohorts visits biomarker measured measurement

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