Identifying the maximum safe dose: A multiple testing approach

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Ludwig A. Hothorn
  • Dieter Hauschke

Research Organisations

External Research Organisations

  • University of California at San Francisco
  • Altana Pharma
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Details

Original languageEnglish
Pages (from-to)15-30
Number of pages16
JournalJournal of Biopharmaceutical Statistics
Volume10
Issue number1
Publication statusE-pub ahead of print - 16 Aug 2006

Abstract

Identifying the maximum safe dose (MAXSD) is an objective of both randomized clinical dose-finding studies for the safety endpoint and toxicological studies. MAXSD is defined as the highest experimental dose with no significant increased safety effect relative to the placebo or control group. In safety assessment, the primary control of the false-negative error rate is more important than that of the false-positive rate. Therefore, we propose a multiple testing procedure for equivalence in the many-to-one design with a priori ordered contrasts (shifted control vs. dose), where the acceptable risk δ is defined in advance. Tests for shifted and ratio hypotheses are presented and discussed.

Keywords

    Intersection-union test, Maximum safe dose, Multiple testing, No-observed-adverse-effect dose (NOAED), Stepwise testing procedure

ASJC Scopus subject areas

Cite this

Identifying the maximum safe dose: A multiple testing approach. / Hothorn, Ludwig A.; Hauschke, Dieter.
In: Journal of Biopharmaceutical Statistics, Vol. 10, No. 1, 16.08.2006, p. 15-30.

Research output: Contribution to journalArticleResearchpeer review

Hothorn LA, Hauschke D. Identifying the maximum safe dose: A multiple testing approach. Journal of Biopharmaceutical Statistics. 2006 Aug 16;10(1):15-30. Epub 2006 Aug 16. doi: 10.1081/BIP-100101010
Hothorn, Ludwig A. ; Hauschke, Dieter. / Identifying the maximum safe dose : A multiple testing approach. In: Journal of Biopharmaceutical Statistics. 2006 ; Vol. 10, No. 1. pp. 15-30.
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