Gema Requena1, Consuelo Huerta2, Helga Gardarsdottir3,4, John Logie5, Rocío González-González2, Victoria Abbing-Karahagopian3, Montserrat Miret6, Cornelia Schneider7, Patrick C Souverein3, Dave Webb5, Ana Afonso3, Nada Boudiaf5, Elisa Martin2, Belén Oliva2, Arturo Alvarez2, Mark C H De Groot3, Andrew Bate8, Saga Johansson9, Raymond Schlienger10, Robert Reynolds11, Olaf H Klungel4,12, Francisco J de Abajo1,13. 1. Pharmacology Section, Department of Biomedical Sciences, School of Medicine and Health Sciences, University of Alcalá, Madrid, Spain. 2. BIFAP Research Unit, Division of Pharmacoepidemiology and Pharmacovigilance, Medicines for Human Use Department, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain. 3. Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands. 4. Department of Clinical Pharmacy, Division Laboratory and Pharmacy, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands. 5. Worldwide Epidemiology, GlaxoSmithKline Research and Development, Uxbridge, Middlesex, UK. 6. Merck KGaA, Geneva, Switzerland. 7. Division of Clinical Pharmacy & Epidemiology, University of Basel, Basel, Switzerland. 8. Epidemiology, Pfizer Ltd, Tadworth, UK. 9. AstraZeneca AB, Mölndal, Sweden. 10. Global Clinical Epidemiology, Novartis Pharma AG, Basel, Switzerland. 11. Epidemiology, Medical Division, Pfizer, New York, NY, USA. 12. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands. 13. Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Madrid, Spain.
Abstract
BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs.
BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs.
Authors: Shirley V Wang; Olga V Patterson; Joshua J Gagne; Jeffrey S Brown; Robert Ball; Pall Jonsson; Adam Wright; Li Zhou; Wim Goettsch; Andrew Bate Journal: Drug Saf Date: 2019-11 Impact factor: 5.606
Authors: A Afonso; S Schmiedl; C Becker; S Tcherny-Lessenot; P Primatesta; E Plana; P Souverein; Y Wang; J C Korevaar; J Hasford; R Reynolds; M C H de Groot; R Schlienger; O Klungel; M Rottenkolber Journal: Eur J Clin Pharmacol Date: 2016-05-24 Impact factor: 2.953
Authors: Rasha Alqdwah-Fattouh; Sara Rodríguez-Martín; Francisco J de Abajo; Diana González-Bermejo; Miguel Gil; Alberto García-Lledó; Francisco Bolúmar Journal: Br J Clin Pharmacol Date: 2020-05-09 Impact factor: 4.335
Authors: Gema Requena; John Logie; Elisa Martin; Nada Boudiaf; Rocío González González; Consuelo Huerta; Arturo Alvarez; David Webb; Andrew Bate; Luis A García Rodríguez; Robert Reynolds; Raymond Schlienger; Helga Gardarsdottir; Mark de Groot; Olaf H Klungel; Fancisco de Abajo; Ian J Douglas Journal: Pharmacoepidemiol Drug Saf Date: 2015-06-26 Impact factor: 2.890