A note on tree gatekeeping procedures in clinical trials

Alex Dmitrienko*, Ajit C. Tamhane, Lingyun Liu, Brian L. Wiens

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3446-3451
Number of pages6
JournalStatistics in Medicine
Issue number17
StatePublished - Jul 30 2008


  • Clinical trials
  • Multiple endpoints
  • Multiple tests

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability


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