title: A case study using the PrOACT-URL and BRAT frameworks for structured benefit risk assessment.
abstract: While benefit-risk assessment is a key component of the drug development and maintenance process, it is often described in a narrative. In contrast, structured benefit-risk assessment builds on established ideas from decision analysis and comprises a qualitative framework and quantitative methodology. We compare two such frameworks, applying multi-criteria decision-analysis (MCDA) within the PrOACT-URL framework and weighted net clinical benefit (wNCB), within the BRAT framework. These are applied to a case study of natalizumab for the treatment of relapsing remitting multiple sclerosis. We focus on the practical considerations of applying these methods and give recommendations for visual presentation of results. In the case study, we found structured benefit-risk analysis to be a useful tool for structuring, quantifying, and communicating the relative benefit and safety profiles of drugs in a transparent, rational and consistent way. The two frameworks were similar. MCDA is a generic and flexible methodology that can be used to perform a structured benefit-risk in any common context. wNCB is a special case of MCDA and is shown to be equivalent to an extension of the number needed to treat (NNT) principle. It is simpler to apply and understand than MCDA and can be applied when all outcomes are measured on a binary scale.
authors.affiliation: Novartis Pharma AG, Statistical Methodology and Consulting, CH-4002 Basel, Switzerland.
authors.forename: Richard
authors.identifier: http://orcid.org/0000-0002-9991-7833
authors.initials: R
authors.lastname: Nixon
authors.affiliation: Bayer Pharma AG, Global Development, D-42096 Wuppertal, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Dierig
authors.affiliation: School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Shahrul
authors.initials: S
authors.lastname: Mt-Isa
authors.affiliation: Bayer Pharma AG, Global Development, D-42096 Wuppertal, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stöckert
authors.affiliation: Health Economics and Decision Science (HEDS), School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Thaison
authors.initials: T
authors.lastname: Tong
authors.affiliation: Bayer Pharma AG, Global Development, D-42096 Wuppertal, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Kuhls
authors.affiliation: Qi Statistics, Penhales House, Ruscombe, Berkshire, RG10 9JN, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Hodgson
authors.affiliation: Astra Zeneca, R&D Global Regulatory Affairs, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Pears
authors.affiliation: School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Waddingham
authors.affiliation: School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Hockley
authors.affiliation: Vigilance & Risk Management of Medicines Division, Medicine and Healthcare Products Regulatory Agency, 151 Buckingham Palace Road, London SW1W 9SZ.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thomson
mesh_terms: D003661:Decision Support Techniques; D004812:Epidemiologic Methods; D006801:Humans; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000628:therapy; D018570:Risk Assessment / Q000379:methods*; D035501:Uncertainty
keywords: BRAT; Benefit-risk; Multicriteria decision analysis; Net clinical benefit; PrOACT-URL; Regulatory decision making