A multiple comparison procedure for three- and four-armed controlled clinical trials.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
L A Hothorn
Publications and source records attributed to L A Hothorn.
Testing dose-response relationships with a priori unknown, possibly nonmonotone shapes.
Usually, a monotone dose-response dependence can be assumed for the simultaneous comparison of increasing levels of a certain drug. However, sometimes a reversal of the dose-response curve is likely to occur at the higher doses. We investigate such violations of the monotonicity assumption. Adequate alternatives are discussed and the "protected trend alternative" is introduced. Together with the umbrella patterns described in the literature, we introduce new testing approaches for both alternatives. P-values/quantiles and power values/sample sizes are made numerically available and hence are readily computed. A short power study and the analysis of a data set from the literature demonstrate the improved behavior of the new methods.
Algorithms↗
Identifying the maximum safe dose: a multiple testing approach.
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.
Animals↗
Report and summary of the major conclusions from statistics in genotoxicity testing working group from the International Workshop on Genotoxicity Test Procedures (IWGTP), March 1999.
A working group of five statisticians experienced in the use of statistical methods in mutagenicity reviewed aspects of the statistical analysis of genotoxicity test procedures. Issues discussed included methods for integrating biological importance and statistical significance, the relationship of the experimental unit to the experimental design, and the impact of new developments in statistics and computing. Three major recommendations were made relating to the need for: (1) the effective use of statistical advice in designing interlaboratory and intralaboratory investigations; (2) the development of appropriate experimental designs for new assays; and (3) education and training in the use of statistical methodology in mutagenicity testing. Environ. Mol. Mutagen. 35:260-263, 2000 Published 2000 Wiley-Liss, Inc.
Guidelines as Topic↗
Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats.
As part of a long-term safety study the bisphosphonate ibandronate was investigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA) and compression tests. Female and male groups of Wistar rats received either vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks orally by gavage. Compared with the control group, bone mineral density, compressive strength and stiffness were significantly higher in ibandronate-treated animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the ibandronate-treated groups. The changes in mechanical properties appear to be due mainly to an increase in bone mass. A highly significant correlation was found between bone mineral density measured either by DXA (r = 0.86) or pQCT (r = 0.85) and maximal strength in vertebral bodies (p < 0.0001 each). In conclusion, we demonstrated that lifelong administration of doses of ibandronate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improves bone quality. Bone mineral density measured either by pQCT or DXA can be used as a predictor for ultimate strength in rat lumbar vertebral bodies after treatment with ibandronate.
Animals↗