An adaptive method for establishing a dose-response relationship.
A multistage sampling method is proposed in dose-response trials, where dose adaptions can be performed in the preplanned adaptive interim analyses. The overall test for proving a dose-response relationship is performed by Fisher's product criterion for the p-values from the separate tests of a dose effect in the disjoint samples at the different stages. Based on these p-values decision boundaries for early stopping with the rejection of the global null hypothesis of no existing dose-response relationship are introduced. The power of the adaptive two-stage procedure using a particular adaptation rule is compared with the power of the test for a linear trend under analysis of variance assumptions in extensive simulations. The bias in estimation is also quantified. This procedure could be used for establishing a dose-response relationship without including a placebo treatment.
D000959:Antihypertensive Agents / Q000008:administration & dosage; D015982:Bias; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000008:administration & dosage; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009010:Monte Carlo Method; D010919:Placebos / Q000627:therapeutic use; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D010919:Placebos; D017315:Cilazapril