Adaptive dose finding based on t-statistic for dose-response trials.
The goals of phase II dose-response studies are to prove that the treatment is effective and to choose the dose for further development. Randomized designs with equal allocation to either a high dose and placebo or to each of several doses and placebo are typically used. However, in trials where response is observed relatively quickly, adaptive designs might offer an advantage over equal allocation. We propose an adaptive design for dose-response trials that concentrates the allocation of subjects in one or more areas of interest, for example, near a minimum clinically important effect level, or near some maximal effect level, and also allows for the possibility to stop the trial early if needed. The proposed adaptive design yields higher power to detect a dose-response relationship, higher power in comparison with placebo, and selects the correct dose more frequently compared with a corresponding randomized design with equal allocation to doses.
Ivanova
Anastasia
A
Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, U.S.A. aivanova@bios.unc.edu
Bolognese
James A
JA
Perevozskaya
Inna
I
D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design