Benefit-risk assessment in a post-market setting: A case study integrating real-life experience into benefit-risk methodology

Christine E. Hallgreen*, Hendrika A. van den Ham, Shahrul Mt-Isa, Simon Ashworth, Richard Hermann, Steve Hobbiger, Davide Luciani, Alain Micaleff, Andrew Thomson, Nan Wang, Tjeerd P. van Staa, Gerald Downey, Ian Hirsch, Kimberley Hockley, Juhaeri Juhaeri, Marilyn Metcalf, Jeremiah Mwangi, Richard Nixon, Ruth Peters, Isabelle StoeckertEd Waddingham, Ioanna Tzoulaki, Deborah Ashby, Lesley Wise

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Purpose: Difficulties may be encountered when undertaking a benefit-risk assessment for an older product with well-established use but with a benefit-risk balance that may have changed over time. This case study investigates this specific situation by applying a formal benefit-risk framework to assess the benefit-risk balance of warfarin for primary prevention of patients with atrial fibrillation. Methods: We used the qualitative framework BRAT as the starting point of the benefit-risk analysis, bringing together the relevant available evidence. We explored the use of a quantitative method (stochastic multi-criteria acceptability analysis) to demonstrate how uncertainties and preferences on multiple criteria can be integrated into a single measure to reduce cognitive burden and increase transparency in decision making. Results: Our benefit-risk model found that warfarin is favourable compared with placebo for the primary prevention of stroke in patients with atrial fibrillation. This favourable benefit-risk balance is fairly robust to differences in preferences. The probability of a favourable benefit-risk for warfarin against placebo is high (0.99) in our model despite the high uncertainty of randomised clinical trial data. In this case study, we identified major challenges related to the identification of relevant benefit-risk criteria and taking into account the diversity and quality of evidence available to inform the benefit-risk assessment. Conclusion: The main challenges in applying formal methods for medical benefit-risk assessment for a marketed drug are related to outcome definitions and data availability. Data exist from many different sources (both randomised clinical trials and observational studies), and the variability in the studies is large.

Original languageEnglish
Pages (from-to)974-983
Number of pages10
JournalPharmacoepidemiology and Drug Safety
Volume23
Issue number9
DOIs
Publication statusPublished - Sept 2014
Externally publishedYes

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