title: Recommendations for benefit-risk assessment methodologies and visual representations.
abstract: OBJECTIVE
  The purpose of this study is to draw on the practical experience from the PROTECT BR case studies and make recommendations regarding the application of a number of methodologies and visual representations for benefit-risk assessment.
  
  
  METHODS
  Eight case studies based on the benefit-risk balance of real medicines were used to test various methodologies that had been identified from the literature as having potential applications in benefit-risk assessment. Recommendations were drawn up based on the results of the case studies.
  
  
  RESULTS
  A general pathway through the case studies was evident, with various classes of methodologies having roles to play at different stages. Descriptive and quantitative frameworks were widely used throughout to structure problems, with other methods such as metrics, estimation techniques and elicitation techniques providing ways to incorporate technical or numerical data from various sources. Similarly, tree diagrams and effects tables were universally adopted, with other visualisations available to suit specific methodologies or tasks as required. Every assessment was found to follow five broad stages: (i) Planning, (ii) Evidence gathering and data preparation, (iii) Analysis, (iv) Exploration and (v) Conclusion and dissemination.
  
  
  CONCLUSIONS
  Adopting formal, structured approaches to benefit-risk assessment was feasible in real-world problems and facilitated clear, transparent decision-making. Prior to this work, no extensive practical application and appraisal of methodologies had been conducted using real-world case examples, leaving users with limited knowledge of their usefulness in the real world. The practical guidance provided here takes us one step closer to a harmonised approach to benefit-risk assessment from multiple perspectives.
authors.affiliation: Worldwide Safety Strategy, Pfizer, New York, NY, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, London, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Waddingham
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, London, UK.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Mt-Isa
authors.affiliation: Pfizer, New York, NY, USA.
authors.forename: Alesia
authors.initials: A
authors.lastname: Goginsky
authors.affiliation: Oncology Signal Detection and Analytics Physician Team Lead, Division of Janssen-Cilag Ltd, Johnson & Johnson, Global Medical Organisation, High Wycombe, Buckinghamshire, UK.
authors.forename: Edmond
authors.initials: E
authors.lastname: Chan
authors.affiliation: Amgen Limited, Cambridge, UK.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Downey
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, London, UK.|Faculty of Health and Medical Science, Department of Pharmacy, CORS, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Hallgreen
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, London, UK.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Hockley
authors.affiliation: Pharmacoepidemiology, Global Pharmacovigilance and Epidemiology, Sanofi, Bridgewater, NJ, USA.
authors.forename: Juhaeri
authors.initials: J
authors.lastname: Juhaeri
authors.affiliation: Benefit-Risk Evaluation, RD Chief Medical Office, GlaxoSmithKline UK Ltd, Uxbridge, UK.
authors.forename: Alfons
authors.initials: A
authors.lastname: Lieftucht
authors.affiliation: Benefit-Risk Evaluation, US Safety Mgmt, RD Chief Medical Office, GSK, NC, USA.
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Metcalf
authors.affiliation: Benefit-Risk Assessment, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Noel
authors.affiliation: Department of Management, London School of Economics, London, UK.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Phillips
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, London, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
authors.affiliation: MerckSerono SA, Geneva, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Micaleff
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000331:legislation & jurisprudence; D003626:Data Display; D003657:Decision Making; D055808:Drug Discovery; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D033161:Government Regulation; D017891:Pharmacoepidemiology / Q000331:legislation & jurisprudence / Q000379:methods*; D018570:Risk Assessment / Q000331:legislation & jurisprudence / Q000379:methods*
keywords: benefit-risk; decision-making; drug development; pharmacoepidemiology; regulation