Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe

Susanne Perez-Gutthann; Manel Pladevall-Vila; Estel Plana Hortoneda; Joan Forns Guzman; Miguel Cainzos Achirica; Cristina Varas-Lorenzo; Miguel Cainzos Achirica; Cristina Varas-Lorenzo; Anton Pottegård; Joelle Asmar; Estel Plana Hortoneda; Lotte Rasmussen; Geoffray Bizouard; Joan Forns Guzman; Maja Hellfritzsch; Kristina Zint; Susanne Perez-Gutthann; Manel Pladevall-Vila

Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases

A case study of dabigatran etexilate in Europe

Cainzos-Achirica, M., Varas-Lorenzo, C., Pottegård, A., Asmar, J., Plana, E., Rasmussen, L., Bizouard, G., Forns, J., Hellfritzsch, M., Zint, K., Perez-Gutthann, S., & Pladevall-Vila, M. (2018). Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe. Pharmacoepidemiology and Drug Safety, 27(7), 713-723. Advance online publication. https://doi.org/10.1002/pds.4416

Copy citation

Abstract

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 conditions 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 anticoagulant 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.