Skip to main content
SpringerLink
Log in

Periodic Benefit-Risk Evaluation Report: A European Union Regulatory Perspective

  • Leading Article
  • Published:
Pharmaceutical Medicine Aims and scope Submit manuscript

Abstract

New European Union (EU) pharmacovigilance legislation, effective from July 2012, introduced new concepts and procedures to optimise the way medicines are regulated within the Union and provided new channels for public health interventions. Triggered by the EU legislation, the work done by the International Conference on Harmonisation (ICH) has provided a common standard for periodic benefit-risk evaluation reporting within the ICH regions. The present paper provides a review of the concepts behind the use of periodic benefit-risk evaluation reports (PBRER) in supporting safety evaluation and assessment of benefit-risk balance and covers essential points in the documentation of safety information, risk evaluation and benefit-risk assessment. The review incorporates the experience to-date with the PBRER at EU level led by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency. The scope of the PBRER, the main content topics and the challenges relevant to the different stakeholders are highlighted together with key success factors for the report to deliver its objectives and maximise the use of the regulatory assessment procedure. It is clear that the PBRER extends beyond new ways of data presentation and analysis and reflects a further shift in pharmacovigilance in the EU towards more integrated benefit-risk assessment of marketed medicines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Notes

  1. A response to a medicinal product which is noxious and unintended [Directive 2001/83/EC Art 1(11)]. Adverse reactions may arise from use of the product within or outside the terms of the marketing authorisation or from occupational exposure [Directive 2001/83/EC Art 101(1)]. Conditions of use outside the marketing authorisation include off-label use, overdose, misuse, abuse and medication errors [5].

References

  1. International Conference of Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonised tripartite guideline periodic benefit-risk evaluation report (PBRER) E2C (R2). http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html. Last accessed 20 July 2014.

  2. International Conference of Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. E2C(R2) Question and answers: periodic benefit-risk evaluation report. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E2C/E2C_R2_QAs_Step4.pdf. Last accessed 20 July 2014.

  3. Guideline on good pharmacovigilance practices (GVP) Module VII—periodic safety update report (Rev 1). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/04/WC500142468.pdf. Last accessed 20 July 2014.

  4. Arlett PR, Kurz X. New approaches to strengthen pharmacovigilance. Drug Discov Today Technol. 2011;8(1):e15–9.

    Article  Google Scholar 

  5. Guideline on good pharmacovigilance practices (GVP) annex I—definitions (Rev 3). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/05/WC500143294.pdf. Last accessed 20 July 2014.

  6. List of European Union reference dates and frequency of submission of periodic safety update reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500133159&mid=WC0b01ac058009a3dc. Last accessed 20 July 2014.

  7. Commission Implementing Regulation (EU) No 520/2012 of 19 June 2012 on the performance of pharmacovigilance activities provided for in Regulation (EC) No 726/2004 of the European Parliament and of the Council and Directive 2001/83/EC of the European Parliament and of the Council. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2012:159:0005:0025:EN:PDF. Last accessed 20 July 2014.

  8. Sabaté M, Pacheco JF, Ballarín E, Ferrer P, Petri H, Hasford J, Schoonen MW, Rottenkolber M, Fortuny J, Laporte JR, Ibáñez L. A compilation of research working groups on drug utilisation across Europe. BMC Res Notes. 2014;13(7):143. doi:10.1186/1756-0500-7-143.

    Article  Google Scholar 

  9. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use Directive 2010/84/EU of the European parliament and of the council of 15 December 2010 amending, as regards pharmacovigilance.

  10. Arlett P, Sarac SB, Thomson A, Davies C, Teixeira T, Blake KV, Stenver D. The European Medicines Agency’s use of prioritised independent research for best evidence in regulatory action on diclofenac. Pharmacoepidemiol Drug Saf. 2014;23(4):431–4.

    Article  CAS  PubMed  Google Scholar 

  11. Arlett P, Portier G, de Lisa R, Blake K, Wathion N, Dogne J-M, Spooner A, Raine J, Rasi G. Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee. Nat Rev Drug Discov (Impact Factor: 33.08). 2014;13(5):395–7.

    Article  CAS  Google Scholar 

  12. Pharmacovigilance Risk Assessment Committee—Rules of procedure. EMA/PRAC/567515/2012. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/03/WC500139609.pdf. Last accessed 20 July 2014.

  13. European Medicines Agency—Work Programme 2014. http://www.ema.europa.eu/docs/en_GB/document_library/Work_programme/2014/03/WC500163394.pdf. Last accessed 20 July 2014.

  14. Prieto Luis, Spooner Almath, Hidalgo-Simon Ana, Rubino Annalisa, Kurz Xavier, Arlett Peter. Evaluation of the effectiveness of risk minimization measures. Pharmacoepidemiol Drug Saf. 2012;21(8):896–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors appreciate the contribution made by Geraldine Portier.

No funding has been received for the preparation of this paper.

Conflict of interest

Peter Arlett, Rodrigo Postigo, Heidi Janssen and Almath Spooner are currently employed by medicines regulatory agencies (European Medicines Agency and Health Products Regulatory Authority) and have been involved in the development of guidelines in relation to the PBRER.

Disclaimer

The views expressed in this article are the personal views of the authors 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.

Author information

Authors and Affiliations

  1. Pharmacovigilance Department, European Medicines Agency, 30 Churchill Place, Canary Wharf, London, E14 5EU, UK

    Peter Arlett & Rodrigo Postigo

  2. Health Products Regulatory Authority, Kevin O’Malley House, The Earlsfort Centre, Earlsfort Terrace, Dublin 2, Ireland

    Almath Spooner

  3. Scientific and Regulatory Management, European Medicines Agency, 30 Churchill Place, Canary Wharf, London, E14 5EU, UK

    Heidi Janssen

Authors
  1. Peter Arlett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rodrigo Postigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heidi Janssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Almath Spooner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Arlett.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arlett, P., Postigo, R., Janssen, H. et al. Periodic Benefit-Risk Evaluation Report: A European Union Regulatory Perspective. Pharm Med 28, 309–315 (2014). https://doi.org/10.1007/s40290-014-0071-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40290-014-0071-5

Keywords

Search

Navigation