119
Views
23
CrossRef citations to date
0
Altmetric
Original Articles

Proof of Hazard and Proof of Safety in Toxicological Studies Using Simultaneous Confidence Intervals for Differences and Ratios to Control

&
Pages 915-933 | Received 01 Oct 2007, Accepted 13 Mar 2008, Published online: 10 Sep 2008

REFERENCES

  • Agresti , A. , Caffo , B. ( 2000 ). Simple and effective confidence intervals for proportions and differences of proportions result from adding two successes and two failures . Am. Stat. 54 : 280 – 288 .
  • Altman , D. G. , Bland , J. M. ( 1995 ). Statistics notes—absence of evidence is not evidence of absence . BM J. 311 : 485 .
  • Armitage , P. ( 1955 ). Tests for linear trends in proportions and frequencies . Biometrics 11 : 375 – 386 .
  • Bailer , A. J. , Oris , J. T. ( 1994 ). Assessing toxicity of pollutants in aquatic systems . In: Lange , N. , Ryan , L. , eds. Case Studies in Biometry . New York : John Wiley , pp. 25 – 40 .
  • Bailer , A. J. , Portier , C. J. ( 1988 ). Effects of treatment-induced mortality and tumor-induced mortality on tests for carcinogenicity in small samples . Biometrics 44 : 417 – 431 .
  • Bofinger , E. , Bofinger , M. ( 1995 ). Equivalence with respect to a control: Stepwise tests . J. Roy. Stat. Soc. B 57 : 721 – 733 .
  • Bretz , F. ( 2006 ). An extension of the Williams trend test to general unbalanced linear models . Comput. Stat. Data Anal. 50 : 1735 – 1748 .
  • Bretz , F. , Hothorn , L. A. ( 2003 ). Statistical analysis of monotone or nonmonotone dose-response data from in vitro toxicological assays . ATLA—Alternatives To Laboratory Animals 31 : 81 – 96 .
  • Bretz , F. , Hothorn , L. A. , Hsu , J. C. ( 2003 ). Identifying effective and/or safe doses by stepwise confidence intervals for ratios . Stat. Med. 22 : 847 – 858 .
  • Bretz , F. , Hothorn , T. , Westfall , P. ( 2002 ). On multiple comparisons in R . R News 2 : 14 – 17 .
  • Bross , I. D. ( 1985 ). Why proof of safety is much more difficult than proof of hazard . Biometrics 41 : 785 – 793 .
  • Cariello , N. F. , Piegorsch , W. W. ( 1996 ). The Ames test: The two-fold rule revisited . Mutation Research-Genetic Toxicology 369 : 23 – 31 .
  • Chen , Y. H. , Zhou , X. H. ( 2006 ). Interval estimates for the ratio and difference of two lognormal means . Stat. Med. 25 : 4099 – 4113 .
  • Dilba , G. , Bretz , E. , Guiard , V. , Hothorn , L. A. ( 2004 ). Simultaneous confidence intervals for ratios with applications to the comparison of several treatments with a control . Methods Inform. Med. 43 : 465 – 469 .
  • Dilba , G. , Bretz , F. , Guiard , V. ( 2006 ). Simultaneous confidence sets and confidence intervals for multiple ratios . J. Stat. Plann. Infer. 136 : 2640 – 2658 .
  • Dilba , G. , Schaarschmidt , F. , Hothorn , L. A. ( 2007 ). Inferences for ratios of normal means . R News 7 : 20 – 23 .
  • Duncan , D. B. (1955). Multiple range and multiple F tests. Biometrics 11(1):1–42.
  • Dunnett , C. W. ( 1955 ). A multiple comparison procedure for comparing several treatments with a control . J. Amer. Stat. Assoc. 50 : 1096 – 1121 .
  • Hasler , M. , Hothorn , L. A. ( 2008 ). Multiple contrast tests in the presence of heteroscedasticity . Biometrical J. (in press) .
  • Hauschke , D. , Kieser , M. , Hothorn , L. A. ( 1999 ). Proof of safety in toxicology based on the ratio of two means for normally distributed data . Biometrical J. 41 : 295 – 304 .
  • Hodges , J. L. , Lehmann , E. L. ( 1963 ). Estimates of location based on rank-tests . Ann. Math. Stat. 34 ( 2 ): 598 – 611 .
  • Holm , S. ( 1979 ). A simple sequentially rejective multiple test procedure . Scnad. J. Stat.
  • Hothorn , L. A. ( 2004 ). Statistische auswerteverfahren . In: Recihl , F. X. , Schwenk , M. , eds. Regulatorische Toxikologie . Heidelberg : Springer , pp. 167 – 181 .
  • Hothorn , T. , Hornik , K. , van de Wiel , M. A. , Zeileis , A. ( 2006 ). A Lego system for conditional inference . Amer. Stat. 60 : 257 – 263 .
  • Hsu , J. C. , Berger , R. L. ( 1999 ). Stepwise confidence intervals without multiplicity adjustment for dose-response and toxicity studies . J. Amer. Stat. Assoc. 94 : 468 – 482 .
  • Kanno , J. , Onyon , L. , Peddada , S. , Ashby , J. , Jacob , E. , Owens , W. ( 2003 ). The oecd program to validate the rat uterotrophic bioassay. Phase 2: Dose response studies . Environ. Health Perspect. 111 : 1530 – 1549 .
  • Leisch , F. ( 2002 ). Sweave part I . R News 2 : 28 – 32 .
  • Lin , K. K. ( 2000 ). Carcinogenicity studies of pharmaceuticals . In Encyclopedia of Biopharmaceutical Statistics . New York : Marcel Dekker , pp. 88 – 103 .
  • Lovell , D. P. , Yoshimura , I. , Hothorn , L. A. , Margolin , B. H. , Soper , K. ( 2000 ). 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 . Environ. Mol. Mutagen. 35 : 260 – 263 .
  • Millard , S. P. ( 1987 ). Proof of safety vs. proof of hazard . Biometrics 43 : 719 – 725 .
  • Munzel , U. , Hothorn , L. A. ( 2001 ). A unifed approach to simultaneous rank test procedures in the unbalanced one-way layout . Biometrical J. 43 : 553 – 569 .
  • Newcombe , R. G. ( 1998 ). Two-sided confidence intervals for the single proportion: Comparison of seven methods . Stat. Med. 17 : 857 – 872 .
  • NTP. ( 2000 ). Toxicology and carcinogenesis studies of methyleugenol in F344/N rats and B6C3F1 mice. Technical report 491 . Washington DC : U.S. Department of Health and Human Services: National Institutes of Health .
  • OECD429 . ( 2002 ). OECD guideline for testing of chemicals: Skin sensitisation: Local lymph node assay. Technical report, OECD/OCDE 429, Paris .
  • OECD479 . ( 1986 ). OECD guideline for testing of chemicals: Genetic toxicology: In vitro sister chromatid exchange assay in mammalian cells. Technical report, OECD, Paris .
  • OECD486 . ( 1997 ). Unscheduled dna synthesis (UDS) test with mammalian liver cells in vivo. Technical report, OECD, Paris .
  • Peddada , S. D. , Dinse , G. E. , Haseman , J. K. ( 2005 ). A survival-adjusted quantal response test for comparing tumour incidence rates . J. R. Stat. Soc. Ser. C Appl. Stati. 54 : 51 – 61 .
  • Ryan , T. P. , Woodall , W. H. ( 2005 ). The most-cited statistical papers . J. Appl. Stat. 32 : 461 – 474 .
  • Saville , D. J. ( 1990 ). Multiple comparison procedures—the practical solution . Amer. Stat. 44 : 174 – 180 .
  • Schaarschmidt , F. ( 2007 ). R-package pairwise CI: Confidence intervals for two sample comparisons, Version: 0.1-4. Technical report . Hannover, Germany : Leibniz University Hannover, Institute of Biostatistics .
  • Schaarschmidt , F. , Sill , M. , Hothorn , L. A. ( 2007a ). Approximate simultaneous confidence intervals for multiple contrasts of binomial proportions and poly-3-adjusted tumour rates. Technical report . Hannover, Germany : Leibniz University Hannover, Institute of Biostatistics .
  • Schaarschmidt , F. , Sill , M. , Hothorn , L. A. (2007b). Poly-k-trend tests for survival adjusted analysis of tumor rates formulated as approximate multiple contrast test. Technical report, Hannover , Germany : Leibniz University Hannover, Institute of Biostatistics.
  • Schulte , A. , Althoff , S. , Ewe , H. B. ( 2002 ). Richter-Reichhelm. Two immunotoxicity ring studies according to OECD TG 407—comparison of data on cyclosporin A and hexachlorobenzene . Regul. Toxicol. Pharmacol. 36 : 12 – 21 .
  • Sill , M. , Schaarschmidt , F. ( 2007 ). Approximate one-sided two-sample confidence limits for the comparison of a treatment versus a near-zero spontaneous rate in control. Technical report . Hannover , Germany : Leibniz University, Institute of Biostatistics .
  • Tamhane , M. C. , Logan , B. R. ( 2004 ). A superiority-equivalence approach to onesided tests on multiple endpoints in clinical trials . Biometrika 91 : 715 – 727 .
  • Tong , Y. L. ( 1969 ). On partitioning a set of normal populations by their locations with respect to a control . Ann. Mathe. Stat. 40 : 1300 – 1324 .
  • Veazie , P. J. ( 2006 ). When to combine hypotheses and adjust for multiple tests . Health Ser. Res. 41 : 804 – 818 .
  • Westfall , P. H. , Young , S. S. ( 1993 ). Resampling-based Multiple Testing . New York : John Wiley & Sons .
  • Williams , D. A. ( 1971 ). Test for differences between treatment means when several dose levels are compared with a zero dose control . Biometrics 27 : 103 – 117 .

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.