Details
| Original language | English |
|---|---|
| Pages (from-to) | 15-30 |
| Number of pages | 16 |
| Journal | Journal of Biopharmaceutical Statistics |
| Volume | 10 |
| Issue number | 1 |
| Publication status | Published - 15 Feb 2000 |
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
- Mathematics(all)
- Statistics and Probability
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Medicine(all)
- Pharmacology (medical)
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In: Journal of Biopharmaceutical Statistics, Vol. 10, No. 1, 15.02.2000, p. 15-30.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Identifying the maximum safe dose
T2 - A multiple testing approach
AU - Hothorn, Ludwig A.
AU - Hauschke, Dieter
N1 - Funding Information: Partly supported by a grant from Volkswagenstiftung, Hannover, Germany, and by a grant from Bundes-institut fuer Gesundheitlichen Verbraucherschutz, Berlin, Germany, for the first author.
PY - 2000/2/15
Y1 - 2000/2/15
N2 - 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.
AB - 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.
KW - Intersection-union test
KW - Maximum safe dose
KW - Multiple testing
KW - No-observed-adverse-effect dose (NOAED)
KW - Stepwise testing procedure
UR - http://www.scopus.com/inward/record.url?scp=0034004937&partnerID=8YFLogxK
U2 - 10.1081/BIP-100101010
DO - 10.1081/BIP-100101010
M3 - Article
C2 - 10709798
AN - SCOPUS:0034004937
VL - 10
SP - 15
EP - 30
JO - Journal of Biopharmaceutical Statistics
JF - Journal of Biopharmaceutical Statistics
SN - 1054-3406
IS - 1
ER -