A note on tree gatekeeping procedures in clinical trials

Stat Med. 2008 Jul 30;27(17):3446-51. doi: 10.1002/sim.3307.

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.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms*
  • Clinical Trials as Topic / methods*
  • Data Interpretation, Statistical*
  • Decision Trees
  • Endpoint Determination / methods*
  • Humans
  • Research Design