Dmitrienko Kordzakhia Tamhane 2011

From MultXpert

Jump to: navigation, search

Dmitrienko, A., Kordzakhia, G., Tamhane, A.C. (2011). Multistage and mixture parallel gatekeeping procedures in clinical trials. Journal of Biopharmaceutical Statistics. 21, 726-747.


Gatekeeping procedures have been developed to solve multiplicity problems arising in clinical trials with hierarchical objectives where the null hypotheses that address these objectives are grouped into ordered families. A general method for constructing multistage parallel gatekeeping procedures was proposed by Dmitrienko Tamhane Wiens 2008. The objective of this paper is to study two related classes of parallel gatekeeping procedures. Restricting to the case of two families of null hypotheses, we first use the mixture method developed in Dmitrienko Tamhane 2011 to define a class of parallel gatekeeping procedures based on the closure principle that can be more powerful than multistage gatekeeping procedures. Secondly, we show that power of multistage gatekeeping procedures can also be improved by using α-exhaustive tests for the component procedures. The resulting procedure still has an attractive multistage structure but with an additional retesting stage which enables retesting of the primary null hypotheses using a more powerful component procedure than the original if all secondary null hypotheses are rejected. Extensions of these results for multiple families are stated. Illustrative examples from clinical trials are given.


Download Dmitrienko Kordzakhia Tamhane 2011.

Review papers and chapters

For more information on gatekeeping procedures in clinical trials, see

Software implementation

Multistage parallel gatekeeping procedures can be implemented using the MultXpert package, see MultXpert package.

Other papers

For information on other publications on gatekeeping procedures in clinical trials, see Gatekeeping Papers.