Determining Drug Exposure Based on Medication Dispensing Data: A Validation Study of Vitamin K Antagonist Treatment Episodes Against INR Records
Pharmacoepidemiology and Drug Safety, vol. 34, pp. e70158
Abstract
BACKGROUND: In pharmaco-epidemiological studies using vitamin K antagonist (VKA) exposure, constructing treatment episodes based on dispensed prescriptions is challenging, particularly due to the large variability in therapeutic dose. OBJECTIVES: To validate different methods of constructing VKA treatment episodes based on dispensed prescriptions, using VKA exposure based on international normalized ratio (INR) measurements as a reference. METHODS: Data from five Dutch anticoagulation clinics were linked to VKA dispensing data from Statistics Netherlands. Three random samples of 10 000 VKA users between 2013 and 2019 were used to compare the construction of VKA treatment episodes based on dispensings, applying fixed or dynamic methods, against the reference of exposure based on INR measurements. A total of 60 different methods were validated by computing the percentage of INR measurements occurring outside dispensing-based VKA treatment episodes, the ratio of VKA-exposed person-time based on dispensings vs. INR measurements, and the number of dispensing-based episodes. RESULTS: Depending on the method used to construct treatment episodes, 14.8%-42.2% of the INR measurements were not covered by a dispensing-based episode. The VKA-exposed person-time ratio ranged between 0.73 and 1.13, and there was substantial variability in the number of dispensing-based episodes. Fixed methods resulted in a lower percentage of INR measurements outside the dispensing-based episodes, a VKA-exposed person-time ratio closer to 1.0, and a lower number of constructed episodes. CONCLUSION: Fixed methods performed better than dynamic methods when classifying VKA exposure based on dispensing data. Our findings may guide other researchers working with VKA dispensing data, especially when the tablets dispensed or the prescribed dose are unavailable.
Authors 18
-
Affiliation as printed
Department of Hematology Erasmus MC, Erasmus University Medical Centre Rotterdam Rotterdam the Netherlands
-
Affiliation as printed
Department of Hematology Erasmus MC, Erasmus University Medical Centre Rotterdam Rotterdam the Netherlands
-
Jamilla Goedegebuur Aachen Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands
Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
-
Qingui Chen Aachen Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands
-
Aalborg University Hospital · Aalborg University
Affiliation as printed
Center for General Practice Aalborg University Aalborg Denmark
Danish Center for Health Services Research, Department of Clinical Medicine Aalborg University Hospital, Aalborg University Aalborg Denmark
-
Affiliation as printed
Danish Center for Health Services Research, Department of Clinical Medicine Aalborg University Hospital, Aalborg University Aalborg Denmark
-
Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of General Practice & Nursing Science Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University Utrecht the Netherlands
-
Denise Abbel Aachen Department of Gerontology and Geriatrics Leiden University Medical Center Leiden The Netherlands Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands LUMC Center for Medicine for Older People LUMC Leiden the Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Gerontology and Geriatrics Leiden University Medical Center Leiden the Netherlands
Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
LUMC Center for Medicine for Older People LUMC Leiden the Netherlands
-
Affiliation as printed
Population Data Science Swansea University Swansea UK
-
Affiliation as printed
Wales Centre for Primary and Emergency Care Research (PRIME Centre Wales), Division of Population Medicine Cardiff University Cardiff UK
-
Johanneke E.A. Portielje Aachen Department of Medical Oncology Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Medical Oncology Leiden University Medical Center Leiden the Netherlands
-
Affiliation as printed
Department of Thrombosis and Anticoagulation Atalmedial Medical Diagnostic Centers Amsterdam the Netherlands
-
Affiliation as printed
Thrombosis Service Star‐shl Rotterdam the Netherlands
-
Affiliation as printed
Thrombosis Service Isala Hospital Zwolle Zwolle the Netherlands
-
Frederikus Albertus Klok Aachen Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
-
Affiliation as printed
Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam the Netherlands
-
Affiliation as printed
Department of Hematology Erasmus MC, Erasmus University Medical Centre Rotterdam Rotterdam the Netherlands
-
Suzanne C. Cannegieter corresponding Aachen Department of Clinical Epidemiology Leiden University Medical Center Leiden The Netherlands Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
Leiden University Medical Center
Affiliation as printed
Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands
Department of Medicine – Thrombosis and Haemostasis Leiden University Medical Center Leiden the Netherlands
Cited by 0 stored of 0
No patents citing this paper on Lens.org (checked 2026-10-11).