Dose selection in seamless phase II/III clinical trials based on efficacy and safety.
Seamless phase II/III clinical trials are attractive in development of new drugs because they accelerate the drug development process. Seamless phase II/III trials are carried out in two stages. After stage 1 (phase II stage), an interim analysis is performed and a decision is made on whether to proceed to stage 2 (phase III stage). If the decision is to continue with further testing, some dose-selection procedure is used to determine the set of doses to be tested in stage 2. In this paper, we propose a dose-selection procedure for binary outcomes in adaptive seamless phase II/III clinical trials that incorporates the dose-response relationship when the experimental treatments are different dose levels of the same drug, and explicitly incorporates both efficacy and safety. The choice of the doses to continue to stage 2 is made by comparing the predictive power of the potential sets of doses, which might continue.
Kimani
Peter K
PK
Department of Statistics, University of Warwick, UK.
Stallard
Nigel
N
Hutton
Jane L
JL
D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006801:Humans; D008508:Medication Errors / Q000517:prevention & control; D015233:Models, Statistical; D016896:Treatment Outcome