Innovative approaches for designing and analyzing adaptive dose-ranging trials.
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.
Bornkamp
Björn
B
University of Dortmund, Dortmund, Germany.
Bretz
Frank
F
Dmitrienko
Alex
A
Enas
Greg
G
Gaydos
Brenda
B
Hsu
Chyi-Hung
CH
König
Franz
F
Krams
Michael
M
Liu
Qing
Q
Neuenschwander
Beat
B
Parke
Tom
T
Pinheiro
José
J
Roy
Amit
A
Sax
Rick
R
Shen
Frank
F
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