TY - JOUR
T1 - Determining Drug Exposure Based on Medication Dispensing Data
T2 - A Validation Study of Vitamin K Antagonist Treatment Episodes Against INR Records
AU - Kempers, Eva K
AU - Visser, Chantal
AU - Goedegebuur, Jamilla
AU - Chen, Qingui
AU - Søgaard, Mette
AU - Ording, Anne Gulbech
AU - van den Dries, Carline
AU - Abbel, Denise
AU - Aldridge, Sarah J
AU - Lifford, Kate J
AU - Portielje, Johanneke E A
AU - Nierman, Melchior C
AU - Boetes-Draisma, Annelies
AU - van de Leur, Sjef J C M
AU - Klok, Frederikus A
AU - Geijteman, Eric C T
AU - Kruip, Marieke J H A
AU - Cannegieter, Suzanne C
N1 - Publisher Copyright:
© 2025 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
PY - 2025/6
Y1 - 2025/6
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Anticoagulants/administration & dosage
KW - Drug Prescriptions/statistics & numerical data
KW - Female
KW - Humans
KW - International Normalized Ratio/statistics & numerical data
KW - Male
KW - Middle Aged
KW - Netherlands/epidemiology
KW - Pharmacoepidemiology/methods
KW - Vitamin K/antagonists & inhibitors
U2 - 10.1002/pds.70158
DO - 10.1002/pds.70158
M3 - Article
C2 - 40389391
SN - 1053-8569
VL - 34
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
IS - 6
M1 - e70158
ER -