TY - JOUR
T1 - Methodological challenges when evaluating potential off‐label prescribing of drugs using electronic health care databases
T2 - A case study of dabigatran etexilate in Europe
AU - Cainzos‐achirica, Miguel
AU - Varas‐lorenzo, Cristina
AU - Pottegård, Anton
AU - Asmar, Joelle
AU - Plana, Estel
AU - Rasmussen, Lotte
AU - Bizouard, Geoffray
AU - Forns, Joan
AU - Hellfritzsch, Maja
AU - Zint, Kristina
AU - Perez‐gutthann, Susana
AU - Pladevall‐vila, Manel
N1 - Funding Information:
The authors would like to thank Elena Rivero, MD, MPH, epidemiologist; Nuria Riera, PhD, epidemiologist; Jaume Aguado, MSc, data analyst; Carla Franzoni, BSc, project manager; Adele Monroe, DVM, MSPH, ELS, medical editor; Jason Mathes, BSc, graphic designer (all from RTI Health Solutions); and Morten Olesen, BSc, data scientist (University of Southern Denmark), for their valuable contributions to this study. The authors would also like to thank the general practitioners contributing information to the CPRD in the United Kingdom and Arlene Gallagher and her colleagues from the CPRD research staff. This study was funded by Boehringer Ingelheim GmbH under a contract including independent publication rights for the research team.
Funding Information:
Miguel Cainzos‐Achirica, Estel Plana, Joan Forns, Susana Perez‐ Gutthann, and Manel Pladevall are fulltime employees of RTI Health Solutions, a unit of RTI International, a non‐profit organization that conducts work for government, public, and private organizations, including pharmaceutical companies. Cristina Varas‐Lorenzo, now retired, was an employee of RTI Health Solutions when this work was conducted. Anton Pottegård reports participation in research projects funded by Alcon, Almirall, Astellas, Astra‐Zeneca, and Servier, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this paper. Lotte Rasmussen has nothing to declare. Maja Hellfritzsch has received speaker honoraria from Bristol‐Myers Squibb and Pfizer. Joelle Asmar and Geoffray Bizouard declare no conflicts of interest relevant to the present work. Kristina Zint is an employee of Boehringer Ingelheim GmbH.
Publisher Copyright:
© 2018 John Wiley & Sons, Ltd.
PY - 2018/7
Y1 - 2018/7
N2 - Purpose: To report and discuss estimated prevalence of potential off‐label use and associated methodological challenges using a case study of dabigatran. Methods: Observational, cross‐sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD‐LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients). Study period: August 2011 to August 2015. Two definitions were used to estimate potential off‐label use: a broad definition of on‐label prescribing using codes for disease indication (eg, atrial fibrillation [AF]), and a restrictive definition excluding patients with condi-tions for which dabigatran is not indicated (eg, valvular AF). Results: Prevalence estimates under the broad definition ranged from 5.7% (CPRD‐HES) to 34.0% (CSD‐LPD) and, under the restrictive definition, from 17.4% (CPRD‐HES) to 44.1% (CSD‐LPD). For the majority of potential off‐label users, no diagnosis potentially related to antico-agulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off‐label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources. Conclusions: Estimates of potential off‐label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES‐linkable estimates are likely to be the most accurate.
AB - Purpose: To report and discuss estimated prevalence of potential off‐label use and associated methodological challenges using a case study of dabigatran. Methods: Observational, cross‐sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD‐LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients). Study period: August 2011 to August 2015. Two definitions were used to estimate potential off‐label use: a broad definition of on‐label prescribing using codes for disease indication (eg, atrial fibrillation [AF]), and a restrictive definition excluding patients with condi-tions for which dabigatran is not indicated (eg, valvular AF). Results: Prevalence estimates under the broad definition ranged from 5.7% (CPRD‐HES) to 34.0% (CSD‐LPD) and, under the restrictive definition, from 17.4% (CPRD‐HES) to 44.1% (CSD‐LPD). For the majority of potential off‐label users, no diagnosis potentially related to antico-agulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off‐label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources. Conclusions: Estimates of potential off‐label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES‐linkable estimates are likely to be the most accurate.
KW - Atrial fibrillation
KW - Dabigatran
KW - Drug utilization
KW - NOACs
KW - Off‐label
KW - Pharmacoepidemiology
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U2 - 10.1002/pds.4416
DO - 10.1002/pds.4416
M3 - Article
C2 - 29570897
AN - SCOPUS:85044309139
SN - 1053-8569
VL - 27
SP - 713
EP - 723
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
IS - 7
ER -