Optimal crossover designs for logistic regression models in pharmacodynamics.
Pharmacodynamics (PD) is the study of the biochemical and physiological effects of drugs. The construction of optimal designs for dose-ranging trials with multiple periods is considered in this paper, where the outcome of the trial (the effect of the drug) is considered to be a binary response: the success or failure of a drug to bring about a particular change in the subject after a given amount of time. The carryover effect of each dose from one period to the next is assumed to be proportional to the direct effect. It is shown for a logistic regression model that the efficiency of optimal parallel (single-period) or crossover (two-period) design is substantially greater than a balanced design. The optimal designs are also shown to be robust to misspecification of the value of the parameters. Finally, the parallel and crossover designs are combined to provide the experimenter with greater flexibility.
Waterhouse
T H
TH
School of Physical Sciences, University of Queensland, Brisbane, Australia. t.waterhouse@gmail.com
Eccleston
J A
JA
Duffull
S B
SB
D000465:Algorithms; D018592:Cross-Over Studies; D016015:Logistic Models; D015233:Models, Statistical; D010600:Pharmacology / Q000706:statistics & numerical data*; D012044:Regression Analysis; D012107:Research Design / Q000706:statistics & numerical data*