Details
| Original language | English |
|---|---|
| Pages (from-to) | 26-34 |
| Number of pages | 9 |
| Journal | Regulatory Toxicology and Pharmacology |
| Volume | 64 |
| Issue number | 1 |
| Early online date | 27 Jun 2012 |
| Publication status | Published - Oct 2012 |
Abstract
Several doses and a control group can be compared under order restriction using the Williams procedure for normally distributed endpoints assuming variance homogeneity. Comparison of the survival functions represents a secondary endpoint in long-term in vivo bioassays of carcinogenicity. Therefore, a Williams-type procedure for the comparison of survival functions is proposed for the assumption of the Cox proportional hazards model or the general frailty Cox model to allow a joint analysis over sex and strains. Interpretation according to both statistical significance and biological relevance is possible with simultaneous confidence intervals for hazard ratios. Related survival data can be analyzed using the R packages survival, coxme, and multcomp. Together with the R packages MCPAN and nparcomp, Dunnett- or Williams-type procedures are now available for the statistical analysis of the following endpoint types in toxicology: (i) normally distributed, (ii) non-normally distributed, (iii) score (ordered categorical) data, (iv) crude proportions, (v) survival functions, and (vi) time-to-tumor data with and without cause-of-death information.
Keywords
- Mortality, Proof of hazard, Proof of safety, Statistical evaluation, Survival
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Toxicology
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In: Regulatory Toxicology and Pharmacology, Vol. 64, No. 1, 10.2012, p. 26-34.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Statistical evaluation of mortality in long-term carcinogenicity bioassays using a Williams-type procedure
AU - Herberich, Esther
AU - Hothorn, Ludwig A.
PY - 2012/10
Y1 - 2012/10
N2 - Several doses and a control group can be compared under order restriction using the Williams procedure for normally distributed endpoints assuming variance homogeneity. Comparison of the survival functions represents a secondary endpoint in long-term in vivo bioassays of carcinogenicity. Therefore, a Williams-type procedure for the comparison of survival functions is proposed for the assumption of the Cox proportional hazards model or the general frailty Cox model to allow a joint analysis over sex and strains. Interpretation according to both statistical significance and biological relevance is possible with simultaneous confidence intervals for hazard ratios. Related survival data can be analyzed using the R packages survival, coxme, and multcomp. Together with the R packages MCPAN and nparcomp, Dunnett- or Williams-type procedures are now available for the statistical analysis of the following endpoint types in toxicology: (i) normally distributed, (ii) non-normally distributed, (iii) score (ordered categorical) data, (iv) crude proportions, (v) survival functions, and (vi) time-to-tumor data with and without cause-of-death information.
AB - Several doses and a control group can be compared under order restriction using the Williams procedure for normally distributed endpoints assuming variance homogeneity. Comparison of the survival functions represents a secondary endpoint in long-term in vivo bioassays of carcinogenicity. Therefore, a Williams-type procedure for the comparison of survival functions is proposed for the assumption of the Cox proportional hazards model or the general frailty Cox model to allow a joint analysis over sex and strains. Interpretation according to both statistical significance and biological relevance is possible with simultaneous confidence intervals for hazard ratios. Related survival data can be analyzed using the R packages survival, coxme, and multcomp. Together with the R packages MCPAN and nparcomp, Dunnett- or Williams-type procedures are now available for the statistical analysis of the following endpoint types in toxicology: (i) normally distributed, (ii) non-normally distributed, (iii) score (ordered categorical) data, (iv) crude proportions, (v) survival functions, and (vi) time-to-tumor data with and without cause-of-death information.
KW - Mortality
KW - Proof of hazard
KW - Proof of safety
KW - Statistical evaluation
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84863853895&partnerID=8YFLogxK
U2 - 10.1016/j.yrtph.2012.06.014
DO - 10.1016/j.yrtph.2012.06.014
M3 - Article
C2 - 22749913
AN - SCOPUS:84863853895
VL - 64
SP - 26
EP - 34
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
SN - 0273-2300
IS - 1
ER -