Details
| Original language | English |
|---|---|
| Pages (from-to) | 995-1006 |
| Number of pages | 12 |
| Journal | Biometrical journal |
| Volume | 42 |
| Issue number | 8 |
| Publication status | Published - 18 Dec 2000 |
Abstract
An important issue in dose finding is whether a further dose increment leads to a relevant increase in efficacy. Clinical efficacy should not be considered by point zero null hypotheses. Instead, shifted hypotheses for the difference or the ratio can be used. Because the a priori definition of a relevance threshold is frequently difficult, confidence intervals should be used for a posteriori interpretation. Sample size estimation - a-priori or by adaptive interim analysis- is inherent, because the effective dose steps are arbitrary in un-designed studies. For simultaneous confidence intervals without order restriction the exact distributions under the null and the alternative hypothesis is proposed for the general unbalanced one-way design.
Keywords
- Dose finding, Effective dose steps, Multivariate t-distribution
ASJC Scopus subject areas
- Mathematics(all)
- Statistics and Probability
- Decision Sciences(all)
- Statistics, Probability and Uncertainty
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In: Biometrical journal, Vol. 42, No. 8, 18.12.2000, p. 995-1006.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - One-sided simultaneous confidence intervals for effective dose steps in unbalanced designs
AU - Hothorn, Ludwig A.
AU - Bretz, Frank
PY - 2000/12/18
Y1 - 2000/12/18
N2 - An important issue in dose finding is whether a further dose increment leads to a relevant increase in efficacy. Clinical efficacy should not be considered by point zero null hypotheses. Instead, shifted hypotheses for the difference or the ratio can be used. Because the a priori definition of a relevance threshold is frequently difficult, confidence intervals should be used for a posteriori interpretation. Sample size estimation - a-priori or by adaptive interim analysis- is inherent, because the effective dose steps are arbitrary in un-designed studies. For simultaneous confidence intervals without order restriction the exact distributions under the null and the alternative hypothesis is proposed for the general unbalanced one-way design.
AB - An important issue in dose finding is whether a further dose increment leads to a relevant increase in efficacy. Clinical efficacy should not be considered by point zero null hypotheses. Instead, shifted hypotheses for the difference or the ratio can be used. Because the a priori definition of a relevance threshold is frequently difficult, confidence intervals should be used for a posteriori interpretation. Sample size estimation - a-priori or by adaptive interim analysis- is inherent, because the effective dose steps are arbitrary in un-designed studies. For simultaneous confidence intervals without order restriction the exact distributions under the null and the alternative hypothesis is proposed for the general unbalanced one-way design.
KW - Dose finding
KW - Effective dose steps
KW - Multivariate t-distribution
UR - http://www.scopus.com/inward/record.url?scp=0034556815&partnerID=8YFLogxK
U2 - 10.1002/1521-4036(200012)42:8<995::AID-BIMJ995>3.0.CO;2-4
DO - 10.1002/1521-4036(200012)42:8<995::AID-BIMJ995>3.0.CO;2-4
M3 - Article
AN - SCOPUS:0034556815
VL - 42
SP - 995
EP - 1006
JO - Biometrical journal
JF - Biometrical journal
SN - 0323-3847
IS - 8
ER -