Operational Definitions of Population, Intervention, Comparison, Outcome for Generating Real-World Evidence Using Korean Health Insurance Claims Sample Data in Integrative Medicine Research: A Methodological Guide

Real-world evidence studies using health insurance claims data are utilized in clinical research. This review provides operational definitions of the study population, intervention/exposure, comparison, and outcomes (PICO) in integrative medicine research (conventional and Korean medicine approaches), with case-based examples. Illustrative claims-based studies using Korean national health insurance data were selected, and how PICO elements had been operationally defined in the research were reviewed. Key variables were categorized into general information, diagnosis information, and medical service information, and mapped to Health Insurance Review and Assessment Service-National Patient Sample and National Health Insurance Service-National Sample Cohort tables to describe their roles in constructing each PICO component. Population was primarily defined using diagnosis information, with variations depending on the breadth of diagnosis code inclusion, while medical service utilization information enabled more refined patient selection. Intervention was mainly operationalized using treatment and prescription codes, service types, and treatment intensity. Comparison groups were constructed by confirming no exposure and improving clinical comparability using confounding-control strategies. Outcomes were defined using combinations of diagnosis records, healthcare utilization events, and mortality data. This review provides a practical framework for operationally defining PICO elements in claims-based real-world evidence studies and may improve rigor and reproducibility in future research.