title: Innovative approaches for designing and analyzing adaptive dose-ranging trials.
abstract: Inadequate selection of the dose to bring forward in confirmatory trials has been identified as one of the key drivers of the decreasing success rates observed in drug development programs across the pharmaceutical industry. In recognition of this problem, the Pharmaceutical Research and Manufacturers of America (PhRMA), formed a working group to evaluate and develop alternative approaches to dose finding, including adaptive dose-ranging designs. This paper summarizes the work of the group, including the results and conclusions of a comprehensive simulation study, and puts forward recommendations on how to improve dose ranging in clinical development, including, but not limited to, the use of adaptive dose-ranging methods.
authors.affiliation: University of Dortmund, Dortmund, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Bornkamp
authors.forename: Frank
authors.initials: F
authors.lastname: Bretz
authors.forename: Alex
authors.initials: A
authors.lastname: Dmitrienko
authors.forename: Greg
authors.initials: G
authors.lastname: Enas
authors.forename: Brenda
authors.initials: B
authors.lastname: Gaydos
authors.forename: Chyi-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Franz
authors.initials: F
authors.lastname: König
authors.forename: Michael
authors.initials: M
authors.lastname: Krams
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Beat
authors.initials: B
authors.lastname: Neuenschwander
authors.forename: Tom
authors.initials: T
authors.lastname: Parke
authors.forename: José
authors.initials: J
authors.lastname: Pinheiro
authors.forename: Amit
authors.initials: A
authors.lastname: Roy
authors.forename: Rick
authors.initials: R
authors.lastname: Sax
authors.forename: Frank
authors.initials: F
authors.lastname: Shen
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004345:Drug Industry; D006801:Humans; D012107:Research Design; D018401:Sample Size