Group sequential Holm and Hochberg procedures

Ajit C. Tamhane*, Dong Xi, Jiangtao Gou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The problem of testing multiple hypotheses using a group sequential procedure often arises in clinical trials. We review several group sequential Holm (GSHM) type procedures proposed in the literature and clarify the relationships between them. In particular, we show which procedures are equivalent or, if different, which are more powerful and what are their pros and cons. We propose a step-up group sequential Hochberg (GSHC) procedure as a reverse application of a particular step-down GSHM procedure. We conducted an extensive simulation study to evaluate the familywise error rate (FWER) and power properties of that GSHM procedure and the GSHC procedure and found that the GSHC procedure controls FWER more closely and is more powerful. All procedures are illustrated with a common numerical example, the data for which are chosen to bring out the differences between them. A real case study is also presented to illustrate application of these procedures. R programs for applying the proposed procedures, additional simulation results, and the proof of the FWER control of the GSHC procedure in a special case are provided in Supplementary Material.

Original languageEnglish (US)
Pages (from-to)5333-5350
Number of pages18
JournalStatistics in Medicine
Issue number24
StatePublished - Oct 30 2021


  • Lan and DeMets flexible boundary
  • O'Brien-Fleming boundary
  • Pocock boundary
  • closed procedure
  • error spending function
  • familywise error rate
  • multiple hypothesis testing

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability


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