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Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics

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

Abstract

Purpose

Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics.

Methods

An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs.

Results

The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster “drug characterization” specifies the nature of the drug. The cluster “dosage” provides information on approved drug dosages and defines corresponding specific conditions. The cluster “clinical pharmacokinetics” includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables.

Conclusion

By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

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Acknowledgements

The authors would like to thank all experts involved in the preliminary development of the e-SmPC model, in particular the e-SmPC consortium: B. Argüello Magaz, P. Arlett, E. N. Arnesen, P. Bastholm, J. J. Bekeringh, L. Brassart, A. Bucsics, O. Bültmann, T. Buxton, P. Cohen, D. Czock, H. G. Eichler, B. Eiermann, F. Fernandez-Llimos, E. van Ganze, B. Godman, L. Grandia, M. Gruvén, L. L. Gustafsson, W. E. Haefeli, A. Helldén, H. Herholz, J. Holmgren, G. Isaksson, A. Körbler, S. Korkmaz, S. Madsen, S. Maxwell, K. Menges, J. A. Rueda Montes, M. L. van der Oppenraay, D. Rodriguez, A. Schoelzky, H. M. Seidling, R. Vander Stichele, A. Veg, H.-G. Wagner, and B. Winbladh.

Authors’ contributions

HGE and WEH are members of the eSmPC Consortium Board and gave the creative force to develop a model for a future eSmPC. HMS, JK, DC, HGE, and WEH developed the first model of drug dosage and clinical pharmacokinetics. AvM, HMS, MM, CMH, and DC refined the suggested model. HMS, WEH, AvM, and DC planned the project; AvM, HMS, MM, CMH, and DC conducted the study; AvM, HMS, and DC analyzed the data. AvM, HMS, DC, and WEH wrote the manuscript. All authors revised and approved the final manuscript.

Authors’ information

The team consists of one employee of the European Medicines Agency (HGE) and clinical experts, including physicians specialized in internal medicine (WEH, DC), clinical pharmacology (WEH, DC), and nephrology (DC), clinical pharmacists (HMS, AvM), and a pharmacy student (CMH) with special expertise in data extraction from SmPCs and in the development of databases for CDSS supporting drug dosage, and IT specialists and experts for CDSS design (JK, MM).

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Anna v. Medem, Hanna M. Seidling, Jens Kaltschmidt, Michael Metzner, Carina M. Hubert, David Czock & Walter E. Haefeli

  2. European Medicines Agency, 30 Churchill Place, Canary Wharf, London, E14 5EU, UK

    Hans-Georg Eichler

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  1. Anna v. Medem
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  2. Hanna M. Seidling
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Corresponding author

Correspondence to Walter E. Haefeli.

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Competing interests

The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.

The authors HGE, CMH, AvM, JK and MM have nothing to disclose. HMS, DC, and WEH report non-financial support from the EMA during the conduct of the study.

The authors declare that they have no competing interests with regard to this work.

Additional information

Anna v. Medem and Hanna M. Seidling contributed equally.

David Czock and Walter E. Haefeli contributed equally.

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Medem, A.v., Seidling, H.M., Eichler, HG. et al. Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics. Eur J Clin Pharmacol 73, 633–641 (2017). https://doi.org/10.1007/s00228-017-2214-6

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  • DOI: https://doi.org/10.1007/s00228-017-2214-6

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