Fallback tests in dose-response clinical trials.
This article introduces a general testing procedure for performing dose-control comparisons in dose-response trials with one or more endpoints. The procedure (termed multi-stage fallback procedure) is an extension of the fallback test proposed by Wiens (2003). The multi-stage fallback procedure features a simple stepwise form and improves the power of dose-control tests at higher doses by taking into account the ordering of the doses. It also serves as an efficient tool for handling multiplicity caused by multiple endpoints. It is shown in this article that the multi-stage fallback procedure can be formulated as a closed testing procedure and thus controls the Type I error rate with respect to multiple dose-control comparisons as well as multiple endpoints. The proposed testing method is illustrated using examples from dose-response clinical trials with single and multiple endpoints.
Dmitrienko
Alex
A
Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. dmitrienko_alex@lilly.com
Wiens
Brian
B
Westfall
Peter
P
D000465:Algorithms; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015233:Models, Statistical; D010919:Placebos / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D012107:Research Design; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D010919:Placebos