Tree-structured gatekeeping tests in clinical trials with hierarchically ordered multiple objectives.
This paper discusses a new class of multiple testing procedures, tree-structured gatekeeping procedures, with clinical trial applications. These procedures arise in clinical trials with hierarchically ordered multiple objectives, for example, in the context of multiple dose-control tests with logical restrictions or analysis of multiple endpoints. The proposed approach is based on the principle of closed testing and generalizes the serial and parallel gatekeeping approaches developed by Westfall and Krishen (J. Statist. Planning Infer. 2001; 99:25-41) and Dmitrienko et al. (Statist. Med. 2003; 22:2387-2400). The proposed testing methodology is illustrated using a clinical trial with multiple endpoints (primary, secondary and tertiary) and multiple objectives (superiority and non-inferiority testing) as well as a dose-finding trial with multiple endpoints.
Dmitrienko
Alex
A
Eli Lilly and Company, Indianapolis, IN 46285, USA. mitrienko_alex@lilly.com
Wiens
Brian L
BL
Tamhane
Ajit C
AC
Wang
Xin
X
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D008076:Cholesterol, HDL / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003663:Decision Trees; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012107:Research Design
D000959:Antihypertensive Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents