A note on tree gatekeeping procedures in clinical trials.
Dmitrienko et al. (Statist. Med. 2007; 26:2465-2478) proposed a tree gatekeeping procedure for testing logically related hypotheses in hierarchically ordered families, which uses weighted Bonferroni tests for all intersection hypotheses in a closure method by Marcus et al. (Biometrika 1976; 63:655-660). An algorithm was given to assign weights to the hypotheses for every intersection. The purpose of this note is to show that any weight assignment algorithm that satisfies a set of sufficient conditions can be used in this procedure to guarantee gatekeeping and independence properties. The algorithm used in Dmitrienko et al. (Statist. Med. 2007; 26:2465-2478) may fail to meet one of the conditions, namely monotonicity of weights, which may cause it to violate the gatekeeping property. An example is given to illustrate this phenomenon. A modification of the algorithm is shown to rectify this problem.
Dmitrienko
Alex
A
Eli Lilly and Company, Indianapolis, IN 46285, USA. dmitrienko_alex@lilly.com
Tamhane
Ajit C
AC
Liu
Lingyun
L
Wiens
Brian L
BL
D000465:Algorithms; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003663:Decision Trees; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D012107:Research Design