摘要:

Based on results of simulation and empirical studies conducted within the divisions of biometrics, center for drug evaluation and research, food and drug administration, and in collaboration with the national toxicology program, the center has recently changed the significance levels for testing positive linear trend in incidence rate for common and rare tumors, respectively, from 0.01 and 0.05 to 0.005 and 0.025. the overall false positive rate resulting from the use of this new rule in the tests for linear trend in a two-species-two-sex study is about 10%, the rate that is judged as the most appropriate in a regulatory setting by the center. this paper descries two of the studies.

ISSN:1054-3406    

DOI:10.1080/10543409808835216

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409808835217

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409808835218

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

Sparse data is a difficulty in the analysis of animal carcinogenicity data:it is difficult to detect effects when the background tumor rates are low. The widely used “Haseman rule” and its variants provide more power to tests with low background rates, while maintaining a degree of control over the global false positive rate. In this article we explore the use of these rules, finding global error rates that are unacceptably high for many animal carcinogenicity studies. We provide alternative weighting methods that correct the deficiencies of the Haseman rule, and apply them to carcinogenicity data from a pharmaceutical company.

ISSN:1054-3406    

DOI:10.1080/10543409808835219

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409808835220

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409808835221

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

In this paper, an exact test for analyzing the homogeneity of treatment effect in adaptive multicenter clinical trials is proposed. Extensive simulation studies are performed to investigate the large sample behavior of a commonly used test statistic for testing homogeneity of treatment effect. When the sample size in each center is large relative to the number of centers the asymptotic null distribution of the test statistic is reasonable. On the other hand when the data are relatively sparse the proposed exact test should be used to incorporate the adaptive nature of the design.

ISSN:1054-3406    

DOI:10.1080/10543409808835222

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

A statistical method for designing screening studies involving several experimental treatments compared to a standard treatment is developed. The screening study identifies the most promising experimental treatments which then undergo more rigorous evaluation in a future larger study. The technique is especially relevant for biopharmaceutical research and development in which phase II clinical trials are conducted to identify the most promising drug regimens which then move on to phase III of clinical development. It is assumed that the underlying distribution of the primary efficacy random variable is a qualitative/quantitative mixture. The proposed methodology involves calculating the probability of

ISSN:1054-3406    

DOI:10.1080/10543409808835223

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

This paper discusses statistical methods for a cardiovascular study in which each of eight animals had a dichotomous outcome observed for each of several treatments. There were five treatments in all shunt, control, two doses of a test drug for potentially causing an unfavorable car- diovascular event and a combination of the test drug and a counteracting agent. Exact conditional methods were used through LogXact a statistical software for exact logistic regression and an alternative framework for performing a large class of nonparametric tests performed by StatXact. The results agreed reasonably with asymptotic methods even though the sample size was small.

ISSN:1054-3406    

DOI:10.1080/10543409808835224

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

The potency of a batch of drug product needs to meet a release limits at the time of release so that the potency at the end of shelf life remains above the lower registration limit (LRL). This article discusses two methods which determine the release limits such that the chance to fail LRL at the end of shelf life of the product will be controlled under a desirable level. In additional to controlling failure rate a method which determines the release limits such that the expected total cost due to rejecting a batch at time zero and at the end of shelf life is minimized. All the methods assume a very flexible sampling schedule and are simple to implement. Each method is illustrated in an example.

ISSN:1054-3406    

DOI:10.1080/10543409808835225

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor