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Ascertainment of acute liver injury in two European primary care databases

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI.

Methods

The Clinical Practice Research Datalink (CPRD) in UK and the Spanish “Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria” (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21 %) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated.

Results

In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95 % in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95 % confidence interval (CI) 2.13–4.25) per 100,000 person-years than CPRD (1.35 (95 % CI 1.03–1.78)).

Conclusions

This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.

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Acknowledgments

We thank Dr Lucia Cea-Soriano for reviewing previous version of the manuscript. The research leading to these results was conducted as part of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT; www.imi-protect.eu) which is a public-private partnership coordinated by the European Medicines Agency. Authors would like to thank the excellent collaboration of physicians in the participating countries, whose contribution in recording their professional practice with high-quality standards makes possible the availability of databases used in this research.

Funding

The PROTECT project has received support from the Innovative Medicines Initiative Joint Undertaking (www.imi.europa.eu) under Grant Agreement no. 115004, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. In the context of the IMI Joint Undertaking (IMI JU), the Department of Pharmacoepidemiology, Utrecht University, received a direct financial contribution from Pfizer. The views expressed are those of the authors only.

Authorship statement

Guarantor of article: Ana Ruigómez

Specific author contributions

Ruigomez A, Garcia Rodriguez LA designed the research study and wrote the protocol.

Ruigomez A, Brauer R and Requena G performed the computer research and analyzed the data.

Ruigomez A, Garcia Rodriguez LA, Brauer R and Bate A drafted the manuscript.

Huerta C, Francisco de Abajo, Requena G and Gil M collected and managed the data in BIFAP and reviewed the manuscript.

Brauer R, Downey G and Feudjo Tepie M collected and managed the data in CPRD.

de Groot M, Schlienger R, Reynolds R and Klungel O reviewed the protocol and manuscript.

All authors contributed to the study design discussions, revising the manuscript, and given the approval of final versions.

Author information

Authors and Affiliations

  1. Centro Español de Investigación Farmacoepidemiologica (CEIFE), Almirante 28, 2°, 28004, Madrid, Spain

    A. Ruigómez & L. A. García Rodríguez

  2. Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

    R. Brauer

  3. Division of Pharmacoepidemiology and Pharmacovigilance, Medicines for Human Use Department, Agencia Española de Medicamentos y Productos Sanitarios (AEMPS), Madrid, Spain

    C. Huerta, G. Requena, M. Gil & Francisco de Abajo

  4. Pharmacology Section, Department of Biomedical Sciences II, University of Alcalá, Madrid, Spain

    Francisco de Abajo

  5. Amgen NV, London, UK

    R. Brauer, G. Downey & M. Feudjo Tepie

  6. Epidemiology, Pfizer Ltd, Walton Oaks, Dorking Road, Tadworth, UK

    A. Bate

  7. Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, The Netherlands

    M. de Groot & O. Klungel

  8. Novartis Pharma AG, Basel, Switzerland

    R. Schlienger

  9. Epidemiology, Pfizer Research & Development, New York, NY, USA

    R. Reynolds

Authors
  1. A. Ruigómez
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  2. R. Brauer
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  3. L. A. García Rodríguez
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  4. C. Huerta
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  5. G. Requena
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  6. M. Gil
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  7. Francisco de Abajo
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  8. G. Downey
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  9. A. Bate
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  10. M. Feudjo Tepie
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  11. M. de Groot
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  12. R. Schlienger
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  13. R. Reynolds
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  14. O. Klungel
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Corresponding author

Correspondence to A. Ruigómez.

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Ruigómez, A., Brauer, R., Rodríguez, L.A.G. et al. Ascertainment of acute liver injury in two European primary care databases. Eur J Clin Pharmacol 70, 1227–1235 (2014). https://doi.org/10.1007/s00228-014-1721-y

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  • DOI: https://doi.org/10.1007/s00228-014-1721-y

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