title: Balancing benefit and risk of medicines: a systematic review and classification of available methodologies.
abstract: BACKGROUND
  The need for formal and structured approaches for benefit-risk assessment of medicines is increasing, as is the complexity of the scientific questions addressed before making decisions on the benefit-risk balance of medicines. We systematically collected, appraised and classified available benefit-risk methodologies to facilitate and inform their future use.
  
  
  METHODS
  A systematic review of publications identified benefit-risk assessment methodologies. Methodologies were appraised on their fundamental principles, features, graphical representations, assessability and accessibility. We created a taxonomy of methodologies to facilitate understanding and choice.
  
  
  RESULTS
  We identified 49 methodologies, critically appraised and classified them into four categories: frameworks, metrics, estimation techniques and utility survey techniques. Eight frameworks describe qualitative steps in benefit-risk assessment and eight quantify benefit-risk balance. Nine metric indices include threshold indices to measure either benefit or risk; health indices measure quality-of-life over time; and trade-off indices integrate benefits and risks. Six estimation techniques support benefit-risk modelling and evidence synthesis. Four utility survey techniques elicit robust value preferences from relevant stakeholders to the benefit-risk decisions.
  
  
  CONCLUSIONS
  Methodologies to help benefit-risk assessments of medicines are diverse and each is associated with different limitations and strengths. There is not a 'one-size-fits-all' method, and a combination of methods may be needed for each benefit-risk assessment. The taxonomy introduced herein may guide choice of adequate methodologies. Finally, we recommend 13 of 49 methodologies for further appraisal for use in the real-life benefit-risk assessment of medicines.
authors.affiliation: School of Public Health, Imperial College London, London, UK.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Mt-Isa
authors.forename: Christine E
authors.initials: CE
authors.lastname: Hallgreen
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Callréus
authors.forename: Georgy
authors.initials: G
authors.lastname: Genov
authors.forename: Ian
authors.initials: I
authors.lastname: Hirsch
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Hobbiger
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Hockley
authors.forename: Davide
authors.initials: D
authors.lastname: Luciani
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Phillips
authors.forename: George
authors.initials: G
authors.lastname: Quartey
authors.forename: Sinan B
authors.initials: SB
authors.lastname: Sarac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stoeckert
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tzoulaki
authors.forename: Alain
authors.initials: A
authors.lastname: Micaleff
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
mesh_terms: D003657:Decision Making; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D006801:Humans; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011788:Quality of Life; D018570:Risk Assessment / Q000145:classification / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations
keywords: benefit-risk; decision-making; framework; medicines; pharmacoepidemiology; qualitative; quantitative; review