Identifying the maximum safe dose: a multiple testing approach.

L A Hothorn; D Hauschke

doi:10.1081/bip-100101010

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PubMed · 10709798

Identifying the maximum safe dose: a multiple testing approach.

L A Hothorn·D Hauschke

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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 delta is defined in advance. Tests for shifted and ratio hypotheses are presented and discussed.

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Animals Antitubercular Agents Diphosphonates Dose-Response Relationship, Drug Female Humans Isoniazid No-Observed-Adverse-Effect Level Normal Distribution Paget Disease, Extramammary Randomized Controlled Trials as Topic Rats Statistics as Topic Statistics, Nonparametric Toxicology Journal Article Research Support, Non-U.S. Gov't

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L A Hothorn, D Hauschke. 2000. Identifying the maximum safe dose: a multiple testing approach.. https://doi.org/10.1081/bip-100101010

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