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

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

来源：Pharmacoepidemiology and Drug Safety, 2014, 23(9): 974-983.

DOI：10.1002/pds.3676

• benefit-risk
• decision making
• medicines
• qualitative
• quantitative
• warfarin
• pharmacoepidemiology

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.

• 出版日期2014-9