Identifying the maximum safe dose: A multiple testing approach

Journal of Biopharmaceutical Statistics

Volumn 10, Issue 1, 2000, Pages 15-30

  Hothorn, Ludwig A ^a,b   Hauschke, Dieter ^c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b LEIBNIZ UNIVERSITY HANNOVER   (Germany)

^c ALTANA PHARMA AG   (Germany)

Author keywords

Intersection union test; Maximum safe dose; Multiple testing; No observed adverse effect dose (NOAED); Stepwise testing procedure

Indexed keywords

ARTICLE; CLINICAL TRIAL; DRUG SAFETY; MAXIMUM PERMISSIBLE DOSE; PRIORITY JOURNAL; RISK; STATISTICAL ANALYSIS; TOXICOLOGY;

ANIMALS; ANTITUBERCULAR AGENTS; DIPHOSPHONATES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; ISONIAZID; NO-OBSERVED-ADVERSE-EFFECT LEVEL; NORMAL DISTRIBUTION; PAGET'S DISEASE, EXTRAMAMMARY; RANDOMIZED CONTROLLED TRIALS; RATS; STATISTICS; STATISTICS, NONPARAMETRIC; TOXICOLOGY;

EID: 0034004937     PISSN: 10543406     EISSN: None     Source Type: Journal    
DOI: 10.1081/BIP-100101010     Document Type: Article

References (55)

1. Tukey JW, Ciminera JL, Heyse JF: "Testing the Statistical Certainty of a Response to Increasing Doses of a Drug," Biometrics, 41, 295-301, 1985.
2. Brown KG, Erdreich LS: "Statistical Uncertainty in the No-Observed-Adverse-Effect Level," Fundam. Appl. Toxicol., 13, 235-244, 1989.
3. Yanagawa T, Kikuchi Y, Brown KG: "Statistical Issues on the No-Observed-Adverse-Effect Level in Categorical Response," Environ. Health Perspect., 102 (suppl 1), 95-101, 1994.
4. Yanagawa T, Kikuchi Y: "Determination of the No-Observed-Adverse-Effect Level by the AIC," Sankhya, B 57, 285-297, 1995.
5. Tamhane AC, Dunnett CW, Wetherington, JD, Green, JW: "Multiple Test Procedure for Identifying a Safe Dose," Preprint, Department of Statistics, Northwestern University, Evanston, IL, 1998.
6. Hothorn LA, Lehmacher W: "A Simple Testing Procedure Control versus k Treatments for One-Sided Ordered Alternatives, with Application in Toxicology," Biometrical J., 33, 179-189, 1991.
7. Tamhane AC, Dunnett CW, Hochberg Y: "Multiple Test Procedures for Dose Finding," Biometrics, 52, 21-37, 1996.
8. Hothorn LA, Neuhäuser M, Koch H-F: "Analysis of Randomized Dose-Finding Studies: Closure Test Modifications Based on Multiple Contrast Tests," Biometrical J., 39, 467-479, 1997.
9. Bross ID: "Why Proof of Safety Is Much More Difficult than Proof of Hazard," Biometrics, 41, 785-793, 1985.
10. Millard SP: "Proof of Safety vs. Proof of Hazard," Biometrics, 43, 719-725, 1987.
11. Stallard N, Whitehead A: "An Alternative Approach to the Analysis of Animal Carcinogenicity Studies," Regul. Toxicol. Pharmacol., 23, 244-248, 1996.
12. Neuhäuser M, Hothorn, LA: "Auswertung der Dosis-Wirkungs-Abhängigkeit des Ames Mutagenitätsassay bei direkter Kontrolle des Konsumentenrisikos." In: Medizinische Forschung und ärztliches Handeln., HJ Trampisch and S Lange, eds., Medizin. Informatik, Biometrie and Epidemiologie, Vol. 80, MVM Medizin Verlag München, Munich, Germany, 113-116, 1995.
13. Neuhäuser M, Hothorn LA: "The Control of the Consumer Risk in the Ames Assay." Drug Inf. J., 31, 363-368, 1997.
14. Hauschke D: "Statistical Proof of Safety in Toxicological Studies," Drug Inf. J., 31, 357-362, 1997.
15. Hauschke D, Hothorn LA: "Safety Assessment in Toxicology Studies: Proof of Safety versus Proof of Hazard," In: Design and Analysis of Animal Studies in Pharmaceutical Development, SC Chow and JP Liu, eds., Marcel Dekker, Inc., New York, 197-226, 1998.
16. Gaylor DW: "The Use of Safety Factors for Controlling Risk," J. Toxicol. Environ. Health, 11, 329-336, 1983.
17. Leisenring W, Ryan L: "Statistical Properties of the NOAEL." Regul Toxicol Pharmacol., 15, 161-171, 1992.
18. Murrell JA, Portier CJ, Morris RW: "Characterization Dose-Response I: Critical Assessment of the Benchmark Dose Concept," Risk Analysis, 18, 13-26, 1998.
19. Bauer P: "A Note on Multiple Testing Procedures in Dose Finding," Biometrics, 53, 1125-1128, 1997.
20. Ruberg SJ: "Contrasts for Identifying the Minimum Effective Dose," J. Am. Stat. Assoc., 84, 816-822, 1989.
21. Fligner MA, Wolfe DA: "Distribution-free Tests for Comparing Several Treatments with a Control," Statist. Neerlandica, 36, 119-127, 1982.
22. Dunnett CW, Tamhane AC: "Step-down Multiple Tests for Comparing Treatments with a Control in Unbalanced One-Way Layouts," Statist. Med., 10, 939-947, 1991.
23. Fraser WD, Stamp TC, Creek RA, Sawyer JP, Picot C: "A Double-blind, Multicentre, Placebo-Controlled Study of Tiludronate in Paget's Disease of Bone," Postgrad. Med. J., 73, 496-502, 1997.
24. Cantor KP, Lynch CF, Hildesheim ME, Dosemeci M, Lubin J, Alavanja M, Craun G: "Drinking Water Source and Chlorination Byproducts I. Risk of Bladder Cancer," Epidemiology, 9, 21-28, 1998.
25. Chen JJ, Kodell RL, Gaylor DW: "Risk Assessment for Nonquantal Effects," In: Toxicology and Risk Assessment, AM Fan and LW Chang, eds., Marcel Dekker, Inc., New York, 503-513, 1996.
26. Hsu JC, Berger RL: "Stepwise Confidence Intervals Without Multiplicity Adjustment for Dose Response, Multiple Endpoints and Toxicity Studies," Technical Report, Department of Statistics, Ohio State University, No. 610, 1997.
27. Crump KS: "Calculation of Benchmark Doses from Continuous Data," Risk Analysis, 15, 79-89, 1995.
28. Shaffer JP: "Modified Sequentially Rejective Multiple Test Procedures," J. Am. Stat. Assoc., 81, 826-831, 1986.
29. Maurer W, Hothorn LA, Lehmacher W: "Multiple Comparisons in Drug Clinical Trials and Preclinical Assays: A priori Ordered Hypotheses," In: Biometrie in der chemisch-pharmazeutischen Industrie, Vol. 6, Vollmar J, ed., Fischer, Stuttgart, Germany, 3-18, 1995.
30. Casella G, Berger RL: Statistical Inference, Wadsworth & Brooks, Pacific Grove, CA, 1990.
31. Dunnett CW, Tamhane AC: "Some New Multiple-Test Procedures for Dose Finding," J. Biopharm. Stat., 8, 353-366, 1998.
32. Bartholomew DJ: "Ordered Test in the Analysis of Variance," Biometrika, 48, 325-332, 1961.
33. Williams DA: "A Test for Differences Between Treatment Means when Several Dose Levels Are Compared with a Zero Dose Control," Biometrics, 27, 103-117, 1971.
34. Mukerjee H, Robertson T, Wright FT: "Multiple Contrast Tests for Testing Against a Simple Tree Ordering," In: Advances in Order Restricted Statistical Inference, R Dykstra, ed., Springer, Berlin, Germany, 203-230, 1986.
35. Tukey JW, Ciminera JL, Heyse JF: "Testing the Statistical Certainty of a Response to Increasing Doses of a Drug," Biometrics, 41, 295-301, 1985.
36. McDermott MP, Mudholkar GS: "A Simple Approach to Testing Homogeneity of Order-Constrained Means", J. Am. Stat. Assoc., 88, 1371-1379, 1993.
37. Hothorn LA, Hilton JF: "Analyzing Real Data Randomized Clinical Dose Finding Studies: Robust Estimation of the Minimum Effective Dose," ASA Proceedings, Biopharm. Section 1998, 91-94, 1999.
38. CPMP Working Party on Efficacy of Medical Products. Note for Guidance: "Biostatistical Methodology in Clinical Trials in Applications for Marketing Authorizations for Medicinal Products," CPMP, London, England, 1994.
39. Hahn GJ, Meeker WQ: Statistical Intervals: Guide for Practitioners, John Wiley & Sons, New York, 1-392, 1991.
40. Gaylor DW, Slikker WL: "Risk Assessment for Neurotoxic Effects," Neurotoxicology 11, 211-218, 1990.
41. Erickson WP, McDonald LL: "Tests for Bioequivalence of Control Media and Test Media in Studies of Toxicity," Environ. Toxicol. Chem., 14, 1247-1256, 1995.
42. Hauschke D, Kieser M, Hothorn LA: "Proof of Safety in Toxicology Based on the Ratio of Two Means for Normally Distributed Data," Biometr. J., 41, 295-304, 1999.
43. Cariello NF, Piegorsch WW: "The Ames Test: The Two-fold Rule Revisited," Mutat. Res., 369, 23-31, 1996.
44. Sasabuchi S: "A Multivariate One-Sided Test with Composite Hypotheses Determined by Linear Inequalities when the Covariance Matrix Has an Unknown Scale Factor," Memoirs of the Faculty of Science, Kyushu University, Series A, Mathematics, Kyushu, Japan, 42, 9-19, 1988.
45. Fieller E: "Some Problems in Interval Estimation," J. Royal Stat. Soc., B16, 175-185, 1954.
46. Kieser M, Hauschke D: "Approximate Sample Sizes for Testing Hypotheses About the Ratio and Difference of Two Means," J. Biopharm. Stat., 9, 641-650, 1999.
47. Berger RL, Hsu JC: "Bioequivalence Trials, Intersection-Union Tests and Equivalence Confidence Sets.," Stat. Sci., 11, 283-302, 1996.
48. Hollander M, Wolfe DA: Nonparametric Statistical Methods, John Wiley & Sons, New York, 1976.
49. Vuorinen J, Tuominen, J: "Fieller's Confidence Intervals for the Ratio of Two Means in the Assessment of Average Bioequivalence from Crossover Data," Stat. Med., 13, 2531-2545, 1994.
50. Blackwelder WC: "Proving the Null Hypothesis in Clinical Trials," Contr. Clin. Trials, 3, 345-353, 1982.
51. Dunnett CW, Gent M: "Significance Testing to Establish Equivalence Between Treatments with Special Reference to Data in the Form of 2 x 2 Tables," Biometrics, 33, 593-602, 1977.
52. Rodary C, Com-Nougue C, Tournade, M: "How to Establish Equivalence between Treatments: A One-Sided Clinical Trial in Paediatric Oncology", Stat. Med., 8, 593-598, 1989.
53. Farrington CP, Manning G: "Test Statistics and Sample Size Formulae for Comparative Binomial Trials with Null-Hypothesis of Non-Zero Risk Differences or Non-Unity Relative Risk," Stat. Med., 9, 1447-1454, 1990.
54. Chan ISF: "Exact Tests of Equivalence and Efficacy with a Non-Zero Lower Bound for Comparative Studies," Stat. Med., 17, 1403-1413, 1998.
55. Tu D: "On the Use of the Ratio or Odds Ratio of Cure Rates in Therapeutic Equivalence Clinical Trials with Binary Endpoints," J. Biopharm. Stat., 8, 263-282, 1998.