Details
| Original language | English |
|---|---|
| Pages (from-to) | 40-53 |
| Number of pages | 14 |
| Journal | Statistics in Biopharmaceutical Research |
| Volume | 3 |
| Issue number | 1 |
| Publication status | Published - 1 Feb 2011 |
Abstract
In a phase II clinical trial it is simultaneously required to prove a drug is truly effective by showing a monotone dose-response relationship and also to obtain information on the recommended dose for the ordinary clinical treatments. Then the multiple comparisons of the interested dose-response patterns are more preferable than an overall testing of the null hypothesis or a fitting of a particular parametric model. In this article the maximal accumulated t statistic (max acc. t-test) proposed for the monotone hypothesis testing is compared with other maximal contrast type tests and shown to be useful also for estimating the dose-response pattern. It is even remarkable that the effect of adding other monotone contrasts to the basic contrasts of max acc. t is so small. The simultaneous lower bounds obtained by the inversion of max acc. t is also shown to be useful for this purpose and has some advantage in giving the lower confidence bound for the mean difference of the estimated optimal dose against the basic dose level. In particular a new formula is obtained in this article for extending the basic lower bounds of max acc. t to all the monotone contrasts by the unique and positive linear combination.
Keywords
- Closed test, Max acc. t test, Monotone contrast, Optimal dose, Simultaneous lower bounds, Stepwise procedure
ASJC Scopus subject areas
- Mathematics(all)
- Statistics and Probability
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
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In: Statistics in Biopharmaceutical Research, Vol. 3, No. 1, 01.02.2011, p. 40-53.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Estimating the dose-response pattern by the maximal contrast type test approach
AU - Hirotsu, Chihiro
AU - Yamamoto, Shoichi
AU - Hothorn, Ludwig A.
PY - 2011/2/1
Y1 - 2011/2/1
N2 - In a phase II clinical trial it is simultaneously required to prove a drug is truly effective by showing a monotone dose-response relationship and also to obtain information on the recommended dose for the ordinary clinical treatments. Then the multiple comparisons of the interested dose-response patterns are more preferable than an overall testing of the null hypothesis or a fitting of a particular parametric model. In this article the maximal accumulated t statistic (max acc. t-test) proposed for the monotone hypothesis testing is compared with other maximal contrast type tests and shown to be useful also for estimating the dose-response pattern. It is even remarkable that the effect of adding other monotone contrasts to the basic contrasts of max acc. t is so small. The simultaneous lower bounds obtained by the inversion of max acc. t is also shown to be useful for this purpose and has some advantage in giving the lower confidence bound for the mean difference of the estimated optimal dose against the basic dose level. In particular a new formula is obtained in this article for extending the basic lower bounds of max acc. t to all the monotone contrasts by the unique and positive linear combination.
AB - In a phase II clinical trial it is simultaneously required to prove a drug is truly effective by showing a monotone dose-response relationship and also to obtain information on the recommended dose for the ordinary clinical treatments. Then the multiple comparisons of the interested dose-response patterns are more preferable than an overall testing of the null hypothesis or a fitting of a particular parametric model. In this article the maximal accumulated t statistic (max acc. t-test) proposed for the monotone hypothesis testing is compared with other maximal contrast type tests and shown to be useful also for estimating the dose-response pattern. It is even remarkable that the effect of adding other monotone contrasts to the basic contrasts of max acc. t is so small. The simultaneous lower bounds obtained by the inversion of max acc. t is also shown to be useful for this purpose and has some advantage in giving the lower confidence bound for the mean difference of the estimated optimal dose against the basic dose level. In particular a new formula is obtained in this article for extending the basic lower bounds of max acc. t to all the monotone contrasts by the unique and positive linear combination.
KW - Closed test
KW - Max acc. t test
KW - Monotone contrast
KW - Optimal dose
KW - Simultaneous lower bounds
KW - Stepwise procedure
UR - http://www.scopus.com/inward/record.url?scp=84867121531&partnerID=8YFLogxK
U2 - 10.1198/sbr.2010.08093
DO - 10.1198/sbr.2010.08093
M3 - Article
AN - SCOPUS:84867121531
VL - 3
SP - 40
EP - 53
JO - Statistics in Biopharmaceutical Research
JF - Statistics in Biopharmaceutical Research
SN - 1946-6315
IS - 1
ER -