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

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

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftPharmacoepidemiology and Drug Safety
Vol/bind27
Udgave nummer7
Sider (fra-til)713-723
ISSN1053-8569
DOI
StatusUdgivet - 2018

Fingeraftryk

Off-Label Use
Databases
Delivery of Health Care
Pharmaceutical Preparations
Research
Primary Health Care
Information Storage and Retrieval
Denmark
Dabigatran
General Practitioners
France
Cross-Sectional Studies
Health

Citer dette

Cainzos-Achirica, Miguel ; Varas-Lorenzo, Cristina ; Pottegård, Anton ; Asmar, Joelle ; Plana, Estel ; Rasmussen, Lotte ; Bizouard, Geoffray ; Forns, Joan ; Hellfritzsch, Maja ; Zint, Kristina ; Perez-Gutthann, Susana ; Pladevall-Vila, Manel. / Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases : A case study of dabigatran etexilate in Europe. I: Pharmacoepidemiology and Drug Safety. 2018 ; Bind 27, Nr. 7. s. 713-723.
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title = "Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe",
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.",
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author = "Miguel Cainzos-Achirica and Cristina Varas-Lorenzo and Anton Potteg{\aa}rd and Joelle Asmar and Estel Plana and Lotte Rasmussen and Geoffray Bizouard and Joan Forns and Maja Hellfritzsch and Kristina Zint and Susana Perez-Gutthann and Manel Pladevall-Vila",
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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, Miguel; Varas-Lorenzo, Cristina; Pottegård, Anton; Asmar, Joelle; Plana, Estel; Rasmussen, Lotte; Bizouard, Geoffray; Forns, Joan; Hellfritzsch, Maja; Zint, Kristina; Perez-Gutthann, Susana; Pladevall-Vila, Manel.

I: Pharmacoepidemiology and Drug Safety, Bind 27, Nr. 7, 2018, s. 713-723.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

PY - 2018

Y1 - 2018

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 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.

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 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.

KW - Atrial fibrillation

KW - Dabigatran

KW - Drug utilization

KW - NOACs

KW - Off-label

KW - Pharmacoepidemiology

U2 - 10.1002/pds.4416

DO - 10.1002/pds.4416

M3 - Journal article

C2 - 29570897

AN - SCOPUS:85044309139

VL - 27

SP - 713

EP - 723

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

IS - 7

ER -