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

I de Greef-van der Sandt; D Newgreen; M Schaddelee; C Dorrepaal; R Martina; A Ridder; R van Maanen

doi:10.1002/cpt.271

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

Clin Pharmacol Ther. 2016 Apr;99(4):442-51. doi: 10.1002/cpt.271. Epub 2015 Nov 13.

Authors

I de Greef-van der Sandt¹, D Newgreen², M Schaddelee², C Dorrepaal², R Martina², A Ridder², R van Maanen²

Affiliations

¹ 3D-PharmXchange, Tilburg, The Netherlands.
² Astellas Pharma Europe, Leiden, The Netherlands.

PMID: 26422298
DOI: 10.1002/cpt.271

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.

Publication types

Clinical Trial, Phase II
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides / administration & dosage
Acetanilides / adverse effects
Acetanilides / therapeutic use*
Adrenergic beta-3 Receptor Agonists / administration & dosage
Adrenergic beta-3 Receptor Agonists / adverse effects
Adrenergic beta-3 Receptor Agonists / therapeutic use*
Decision Support Techniques*
Drug Dosage Calculations
Drug Monitoring
Drug Therapy, Combination
Female
Humans
Male
Muscarinic Antagonists / administration & dosage
Muscarinic Antagonists / adverse effects
Muscarinic Antagonists / therapeutic use*
Risk Assessment
Risk Factors
Solifenacin Succinate / administration & dosage
Solifenacin Succinate / adverse effects
Solifenacin Succinate / therapeutic use*
Thiazoles / administration & dosage
Thiazoles / adverse effects
Thiazoles / therapeutic use*
Treatment Outcome
Urinary Bladder, Overactive / drug therapy*
Urinary Bladder, Overactive / physiopathology
Urological Agents / administration & dosage
Urological Agents / adverse effects
Urological Agents / therapeutic use*

Substances

Acetanilides
Adrenergic beta-3 Receptor Agonists
Muscarinic Antagonists
Thiazoles
Urological Agents
Solifenacin Succinate
mirabegron