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Real-Life and RCT Participants: Alendronate Users Versus FITs’ Trial Eligibility Criterion

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Abstract

We aimed to characterize incident users of alendronate from Denmark and Spain, and investigate their eligibility for participation in the pivotal Fracture Intervention Trial (FIT). This is an international cross-sectional study, where the data were obtained from the SIDIAP database (Sistema d’Informació per al Desenvolupament de l’Investigació en Atenció Primària) from Catalonia (Spain) and the Danish Health Registries (DHR). This study included patients who were incident users of alendronate, ≥40 years old with no history of Paget’s disease. Our measurements were the proportion of incident users of alendronate who were not eligible to participate in FIT. 14,316 and 21,221 subjects initiated alendronate in 2006–2007 (SIDIAP) and 2005–2006 (DHR), respectively. SIDIAP and DHR alendronate user cohorts had 2347 (16.4 %) and 5275 (24.9 %) subjects aged >80 years old, reported 9 (0.1 %) and 91 (0.4 %) diagnoses of myocardial infarction, 423 (3 %) and 368 (1.7 %) of erosive gastro-intestinal disease, 200 (1.4 %) and 1109 (5.2 %) of dyspepsia, and 349 (2.4 %) and 149 (0.7 %) of metabolic bone disease, all of which were exclusion criteria in FIT. Men [3818 (26.7 %) in SIDIAP and 3885 (18.3 %) in DHR] and glucocorticoid users [1229 (8.6 %) in SIDIAP and 4716 (22.2 %) in DHR] were also excluded from the FIT trial. Overall, 3447 (35.4 %) SIDIAP and 6228 (44.5 %) (when not considering men and glucocorticoid users) DHR of incident alendronate users would have been excluded from FIT. One in two real-life users of alendronate exhibited one or more clinical characteristics that would have led to them being excluded from the FIT trial.

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Acknowledgments

We would like to acknowledge the health professionals (general practitioners and nurses) responsible for the collection of these data, as well as to the patients involved. DPA receives funding from the National Institute for Health Research Clinician Scientist award scheme. ADP affirms that he has listed everyone who contributed significantly to the work. All authors had access to all the study data, take responsibility for the accuracy of the analysis, and had authority over manuscript preparation and the decision to submit the manuscript for publication.

Author’s Contributors Statement

DPA, BA, and CR: Data extraction, statistical analysis, and manuscript preparation. DPA: Study design, data analysis, and interpretation and manuscript preparation. CR: data interpretation and manuscript preparation. MKJ, CC, ADP: study design and manuscript preparation. AP, PS, and TVS: manuscript preparation. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

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Authors and Affiliations

  1. GREMPAL Research Group, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Universitat Autònoma de Barcelona, Gran Via Corts Catalanes 587, 08007, Barcelona, Spain

    Carlen Reyes & Daniel Prieto-Alhambra

  2. Clinical Pharmacology, Department of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9B, 2nd Floor, 5000, Odense C, Denmark

    Anton Pottegård

  3. Department of Endocrinology, Research Centre for Ageing and Osteoporosis, Rigshospitalet-Glostrup Hospital, Nordre Ringvej 69, Glostrup, 2600, Copenhagen, Denmark

    Peter Schwarz

  4. Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, University of oxford, Windmill Road, Oxford, OX3 7LD, UK

    M. Kassim Javaid, Cyrus Cooper & Daniel Prieto-Alhambra

  5. MRC Lifecourse Epidemiology Unit, Southampton General Hospital, University of Southampton, Southampton, SO16 6YD, UK

    M. Kassim Javaid, Cyrus Cooper & Daniel Prieto-Alhambra

  6. Health eResearch Centre, Farr Institute for Health Informatics Research, University of Manchester, 1.003 Vaughan House, Portsmouth Road, Manchester, M13 9PL, UK

    Tjeerd P. Van Staa

  7. Department of Pharmacoepidemiology, Utrecht University, Utrecht, The Netherlands

    Tjeerd P. Van Staa

  8. National Institute for Health Research Nutrition Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, SO16 6YD, UK

    Cyrus Cooper

  9. Musculoskeletal Research Unit and RETICEF, IMIM Research Foundation, Parc de Salut Mar and Instituto de Salud Carlos III, Parc de Recerca Biomèdica de Barcelona, Universitat Autònoma de Barcelona, c/Dr. Aiguader 88, 08003, Barcelona, Spain

    Adolfo Diez-Perez & Daniel Prieto-Alhambra

  10. Department of Medicine, Holbæk Hospital, Smedelundsgade 60, Holbæk, 4300, Holbæk, Denmark

    Bo Abrahamsen

  11. OPEN Odense Patient Data Explorative Network, Institute of Clinical Research, Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 9 A, 3. Sal., 5000, Odense C, Denmark

    Bo Abrahamsen

Authors
  1. Carlen Reyes
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  2. Anton Pottegård
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  3. Peter Schwarz
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  4. M. Kassim Javaid
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  5. Tjeerd P. Van Staa
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  6. Cyrus Cooper
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  7. Adolfo Diez-Perez
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  8. Bo Abrahamsen
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  9. Daniel Prieto-Alhambra
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Corresponding author

Correspondence to Adolfo Diez-Perez.

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Conflict of interest

P. S, C. R, and A. P declare that they have no conflict of interest; D. P. A: Scientific Coordinator of the SIDIAP Database. Unrestricted research grants from Amgen and Bioiberica; A.D.P: speaker or advisor for Lilly, Amgen, UCB, Active Life Sci; C.C: received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, Eli Lilly, GSK, Medtronic, Merck, MSD, Novartis, Pfizer, Roche, Servier and Takeda. (outside the submitted work); K.J: personal fees from consultancy, lecture fees and/or honoraria from AMGEN, GSK, Eli Lilly, Novartis, Servier, Medtronic and Roche outside the submitted work; B.A: research grants from or served as an investigator in studies for Novartis, Takeda, NPS Pharmaceuticals and Amgen; T.V.S: advisory boards for GSK and Boehringer and advice to Laser Rx on epidemiological and pragmatic trial methods outside the submitted work.

Human and Animal Rights

For this type of study formal consent is not required.

Informed Consent

Patient consent was not required (anonymised retrospective data).

Additional information

Bo Abrahamsen and Daniel Prieto-Alhambra are Joint senior authors.

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Reyes, C., Pottegård, A., Schwarz, P. et al. Real-Life and RCT Participants: Alendronate Users Versus FITs’ Trial Eligibility Criterion. Calcif Tissue Int 99, 243–249 (2016). https://doi.org/10.1007/s00223-016-0141-7

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  • DOI: https://doi.org/10.1007/s00223-016-0141-7

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