title: A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.
abstract: A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs.
authors.affiliation: 3D-PharmXchange, Tilburg, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: de Greef-van der Sandt
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Newgreen
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schaddelee
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Dorrepaal
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Martina
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Ridder
authors.affiliation: Astellas Pharma Europe, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Maanen
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003661:Decision Support Techniques; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D000069464:Solifenacin Succinate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D064804:Urological Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D018727:Muscarinic Antagonists; D013844:Thiazoles; D064804:Urological Agents; D000069464:Solifenacin Succinate; C520025:mirabegron