DEFINING ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) IN REAL-WORLD RESEARCH: AN ANALYSIS OF CONCEPTUAL AND OPERATIONAL DEFINITION VARIABILITY
Author(s)
Jared H. Kamauu, BFA1, Michael Buck, PhD2, Craig G Parker, MD, MS3, Allise G Kamauu, MS4, Aimee Harrison, MFA2, Scott L. DuVall, PhD5, Aaron Kamauu, MPH, MS, MD6;
1Navidence Inc, Knowledge Engineer, Salt Lake City, UT, USA, 2Navidence, Aurora, CO, USA, 3Navidence, Sandy, UT, USA, 4Navidence, Salt Lake City, UT, USA, 5PurpleLab Healthcare Analytics, Taylorsville, UT, USA, 6Navidence, Inc., Bountiful, UT, USA
1Navidence Inc, Knowledge Engineer, Salt Lake City, UT, USA, 2Navidence, Aurora, CO, USA, 3Navidence, Sandy, UT, USA, 4Navidence, Salt Lake City, UT, USA, 5PurpleLab Healthcare Analytics, Taylorsville, UT, USA, 6Navidence, Inc., Bountiful, UT, USA
OBJECTIVES: In Real-world research (RWR), complex clinical concepts, composed of multiple composite conditions, often define cohort phenotypes. Meaningful results depend on consistent conceptual and computable operational definitions (CODefs). However, variance in these definitions, and the code lists used, may exist for some of these clinical concepts. This assessment demonstrates variations in CODefs from reputable sources and RWR publications on patients with Atherosclerotic Cardiovascular Disease (ASCVD).
METHODS: We reviewed literature and clinical references (e.g., American Heart Association) to identify clinical definitions of ASCVD. We extracted and analyzed multiple medical conditions used in ASCVD definitions, including peripheral artery disease (PAD) and myocardial infarction (MI). Our analysis included assessment of combinations of these conditions. When available, code lists were also compared.
RESULTS: 10 references were analyzed, from which 20 medical conditions were identified as part of an ASCVD definition, representing 9 different combinations. The most common condition, PAD, was present in all definitions, followed by ischemic stroke (8/10), and MI (7/10). 7 conditions appeared in ≤2 definitions. 5 references published operational definitions covering 13 conditions. Across references, 4 conditions showed significant code list variation (min. pairwise Jaccard < 0.4), 3 showed minimal variation (min. pairwise Jaccard > 0.8), and the remainder showed moderate variation with potential cohort impact. For PAD, 360 distinct codes were identified, with significant variation across studies (52-351 codes). The two smallest PAD code lists contained a combined 60 codes, 59 of which were also in the three largest lists and 1 that was not.
CONCLUSIONS: ASCVD is a common concept studied in RWR. However, the variance in conceptual and operational definitions introduces challenges for consistent interpretation and extrapolation of results. Understanding this variance is essential in RWR as “small difference in the choice of operational definition ⋯ may have a large impact on study results.” [FDA 2023]
METHODS: We reviewed literature and clinical references (e.g., American Heart Association) to identify clinical definitions of ASCVD. We extracted and analyzed multiple medical conditions used in ASCVD definitions, including peripheral artery disease (PAD) and myocardial infarction (MI). Our analysis included assessment of combinations of these conditions. When available, code lists were also compared.
RESULTS: 10 references were analyzed, from which 20 medical conditions were identified as part of an ASCVD definition, representing 9 different combinations. The most common condition, PAD, was present in all definitions, followed by ischemic stroke (8/10), and MI (7/10). 7 conditions appeared in ≤2 definitions. 5 references published operational definitions covering 13 conditions. Across references, 4 conditions showed significant code list variation (min. pairwise Jaccard < 0.4), 3 showed minimal variation (min. pairwise Jaccard > 0.8), and the remainder showed moderate variation with potential cohort impact. For PAD, 360 distinct codes were identified, with significant variation across studies (52-351 codes). The two smallest PAD code lists contained a combined 60 codes, 59 of which were also in the three largest lists and 1 that was not.
CONCLUSIONS: ASCVD is a common concept studied in RWR. However, the variance in conceptual and operational definitions introduces challenges for consistent interpretation and extrapolation of results. Understanding this variance is essential in RWR as “small difference in the choice of operational definition ⋯ may have a large impact on study results.” [FDA 2023]
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
MSR49
Topic
Methodological & Statistical Research
Topic Subcategory
Confounding, Selection Bias Correction, Causal Inference
Disease
SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory)