Details
Original language | English |
---|---|
Pages (from-to) | 137-154 |
Number of pages | 18 |
Journal | Fundamental and Clinical Pharmacology |
Volume | 21 |
Issue number | 2 |
Publication status | Published - 7 Feb 2007 |
Abstract
Multiplicity adjustment in general is currently a controversial topic. This review focuses on the proof of efficacy in randomized clinical trials. The ICH guidelines mandate control of the familywise error rate. Confidence intervals are clinically more appropriate than P-values or yes/no decisions. Therefore, simultaneous confidence intervals are proposed for several designs and aims in clinical trials. The computation of simultaneous confidence intervals for the difference or the ratio is demonstrated by means of real data examples using the R-packages multcomp and mratios. A special problem is the evaluation of dose-finding trials with and without the assumption that the effects increase with increasing doses. Simultaneous intervals are presented not only for one-way layouts and normal distributed endpoints, but also for higher way layouts, generalized linear models, and mixed models. Under importance ordering, the conditional testing of all hypotheses at level α will be shown using the intersection-union test principle. Other multiplicity issues (i.e. multiple endpoints, multiple analyses, and subgroup analyses) are discussed.
Keywords
- Multi-armed clinical trials, Multiplicity, Simultaneous confidence intervals, Statistics
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Medicine(all)
- Pharmacology (medical)
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In: Fundamental and Clinical Pharmacology, Vol. 21, No. 2, 07.02.2007, p. 137-154.
Research output: Contribution to journal › Review article › Research › peer review
}
TY - JOUR
T1 - How to deal with multiple treatment or dose groups in randomized clinical trials?
AU - Hothorn, L. A.
PY - 2007/2/7
Y1 - 2007/2/7
N2 - Multiplicity adjustment in general is currently a controversial topic. This review focuses on the proof of efficacy in randomized clinical trials. The ICH guidelines mandate control of the familywise error rate. Confidence intervals are clinically more appropriate than P-values or yes/no decisions. Therefore, simultaneous confidence intervals are proposed for several designs and aims in clinical trials. The computation of simultaneous confidence intervals for the difference or the ratio is demonstrated by means of real data examples using the R-packages multcomp and mratios. A special problem is the evaluation of dose-finding trials with and without the assumption that the effects increase with increasing doses. Simultaneous intervals are presented not only for one-way layouts and normal distributed endpoints, but also for higher way layouts, generalized linear models, and mixed models. Under importance ordering, the conditional testing of all hypotheses at level α will be shown using the intersection-union test principle. Other multiplicity issues (i.e. multiple endpoints, multiple analyses, and subgroup analyses) are discussed.
AB - Multiplicity adjustment in general is currently a controversial topic. This review focuses on the proof of efficacy in randomized clinical trials. The ICH guidelines mandate control of the familywise error rate. Confidence intervals are clinically more appropriate than P-values or yes/no decisions. Therefore, simultaneous confidence intervals are proposed for several designs and aims in clinical trials. The computation of simultaneous confidence intervals for the difference or the ratio is demonstrated by means of real data examples using the R-packages multcomp and mratios. A special problem is the evaluation of dose-finding trials with and without the assumption that the effects increase with increasing doses. Simultaneous intervals are presented not only for one-way layouts and normal distributed endpoints, but also for higher way layouts, generalized linear models, and mixed models. Under importance ordering, the conditional testing of all hypotheses at level α will be shown using the intersection-union test principle. Other multiplicity issues (i.e. multiple endpoints, multiple analyses, and subgroup analyses) are discussed.
KW - Multi-armed clinical trials
KW - Multiplicity
KW - Simultaneous confidence intervals
KW - Statistics
UR - http://www.scopus.com/inward/record.url?scp=33947632910&partnerID=8YFLogxK
U2 - 10.1111/j.1472-8206.2007.00469.x
DO - 10.1111/j.1472-8206.2007.00469.x
M3 - Review article
C2 - 17391286
AN - SCOPUS:33947632910
VL - 21
SP - 137
EP - 154
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
SN - 0767-3981
IS - 2
ER -