Evaluation of a combination drug with multiple doses in unbalanced factorial design clinical trials.
Flexibilities for sample size allocation are often demanded for achieving multiple study objectives in combination drug trials. The global tests of Hung, Chi and Lipicky are extended for analysis of unbalanced factorial design trials to test the hypothesis that at least one of the non-zero dose combinations of two drugs is more effective than the respective component doses. When the dose combinations have heterogeneous effect sizes, an unbalanced design may induce greater power than the balanced design. An adjusted p-value approach is proposed for testing the individual dose combinations under the condition that the maximum type I error probability is protected.
Division of Biometrics I, Office of Biostatistics, CDER, FDA, HFD-710, Room 5062, Woodmont II, 1451 Rockville Pike, Rockville, MD 20852, USA. hung@cder.fda.gov
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D000465:Algorithms; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D003627:Data Interpretation, Statistical; D004232:Diuretics / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D015233:Models, Statistical; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010919:Placebos; D016012:Poisson Distribution; D011336:Probability; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D018401:Sample Size
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D004364:Pharmaceutical Preparations; D010919:Placebos