title: Identifying the maximum safe dose: a multiple testing approach.
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.
authors.affiliation: Department of Epidemiology and Biostatistics, University of California at San Francisco, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Hothorn
authors.forename: D
authors.initials: D
authors.lastname: Hauschke
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity; D004164:Diphosphonates / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000031:analogs & derivatives / Q000633:toxicity; D019055:No-Observed-Adverse-Effect Level; D016011:Normal Distribution; D010145:Paget Disease, Extramammary / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D051381:Rats; D013223:Statistics as Topic / Q000379:methods*; D018709:Statistics, Nonparametric; D014116:Toxicology / Q000379:methods*
chemical_list: D000995:Antitubercular Agents; D004164:Diphosphonates; C058651:tiludronic acid; C028354:aconiazide; D007538:Isoniazid