title: Structured Benefit-risk assessment: a review of key publications and initiatives on frameworks and methodologies.
abstract: Introduction The conduct of structured benefit-risk assessment (BRA) of pharmaceutical products is a key area of interest for regulatory agencies and the pharmaceutical industry. However, the acceptance of a standardized approach and implementation are slow. Statisticians play major roles in these organizations, and have a great opportunity to be involved and drive the shaping of future BRA. Method We performed a literature search of recent reviews and initiatives assessing BRA methodologies, and grouped them to assist those new to BRA in learning, understanding, and choosing methodologies. We summarized the key points and discussed the impact of this emerging field on various stakeholders, particularly statisticians in the pharmaceutical industry. Results We provide introductory, essential, special interest, and further information and initiatives materials that direct readers to the most relevant materials, which were published between 2000 and 2013.  Based on recommendations in these materials we supply a toolkit of advocated BRA methodologies. Discussion Despite initiatives promoting these methodologies, there are still barriers, one of which being the lack of a consensus on the most appropriate methodologies among stakeholders. However, this opens up opportunities, for statisticians in the pharmaceutical industry especially, to champion appropriate BRA methodology use throughout the pharmaceutical product lifecycle. Conclusions This article may serve as a starting point for discussions and to reach a mutual consensus for methodology selection in a particular situation. Regulators and pharmaceutical industry should continue to collaborate to develop and take forward BRA methodologies, and by clear communication develop a mutual understanding of the key issues. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Mt-Isa
authors.affiliation: Biometrics, Abbott Healthcare Products B.V, Weesp, The Netherlands.
authors.forename: Mario
authors.initials: M
authors.lastname: Ouwens
authors.affiliation: Department of Biostatistics, Institut de Recherches Internationales Servier, Suresnes, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Robert
authors.affiliation: Global Integrated Analysis and Life Cycle Management Statistics, Bayer Healthcare, Wuppertal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gebel
authors.affiliation: Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schacht
authors.affiliation: Biometrics and Information Sciences, AstraZeneca LP, Gaithersburg, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Hirsch
mesh_terms: D017277:Drug Approval / Q000379:methods*; D004345:Drug Industry / Q000379:methods* / Q000639:trends; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000517:prevention & control*; D006801:Humans; D018570:Risk Assessment / Q000379:methods / Q000639:trends
keywords: benefit-risk; pharmaceutical; regulatory; review; statistics