title: A note on tree gatekeeping procedures in clinical trials.
abstract: 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.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA. dmitrienko_alex@lilly.com
authors.forename: Alex
authors.initials: A
authors.lastname: Dmitrienko
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Tamhane
authors.forename: Lingyun
authors.initials: L
authors.lastname: Liu
authors.forename: Brian L
authors.initials: BL
authors.lastname: Wiens
mesh_terms: 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