摘要:

Nonparametric methods are presented for the analysis of the two-treatment, two-period crossover design with multivariate response. After forming within-subject sums and differences, the usual tests, including those for carry-over effects and direct treatment effects, can be constructed using a multivariate analysis of variance. When the assumptions relevant to traditional analysis are in question, multivariate nonparametric tests based on ranks provide a realistic alternative. However, multivariate response gives rise to a wider class of hypotheses than is seen in crossover designs with univariate response. We discuss these hypotheses and formulate nonparametric tests for associated analyses.

ISSN:1054-3406    

DOI:10.1080/10543409308835045

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

We consider the problem of stopping a clinical trial before its scheduled termination due to the apparent ineffectiveness of the experimental therapy, as compared with a control. We propose a simple-to-implement, intuitive decision rule based on the unadjusted attained significance levels from any appropriate statistical test. The proposed procedure may be used at any time during the study as an aid to help determine whether the study of an experimental treatment should be terminated early with the conclusion of treatment ineffectiveness. Much of the power of the usual fixed-sample test is retained while maintaining the nominal test size.

ISSN:1054-3406    

DOI:10.1080/10543409308835046

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

A nonlinear mixed-effects model suitable for characterizing repeated measurement data is described. The model allows dependence of random coefficients on covariate information and accommodates general specifications of a common intraindividual covariance structure, such as models for variance within individuals that depend on individual mean response and autocorrelation. Two classes of procedures for estimation in this model are described, which incorporate estimation of unknown parameters in the assumed intraindividual covariance structure. The procedures are straightforward to implement using standard statistical software. The techniques are illustrated by examples in growth analysis and assay development.

ISSN:1054-3406    

DOI:10.1080/10543409308835047

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

The use of a composite response to estimate the relative potency in a multivariate parallel–line bioassay is described by Finney (1). Occasionally a multivariate bioassay has multiple drugs also. Such a situation arises, for example, when a treatment contains several drugs. A procedure for combining multiple responses and combining multiple drugs is proposed in this paper, in order to obtain point and interval estimates of the relative potency. A composite response and a composite dose level for this purpose are obtained by using canonical analysis.

ISSN:1054-3406    

DOI:10.1080/10543409308835048

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

Results of clinical studies are often obscured by the fact that some of the subjects improve with treatment while others do not. As a consequence, for example, we may obtain a contaminated distribution in a treatment group, having one component similar to the entire distribution for a control group and the other shifted by the treatment effect. Maximum-likelihood estimation and the likelihood ratio test for investigating the proportion of responders together with the treatment effect are based on asymptotic theory and use iterative maximization techniques. We investigate the sampling distribution of the estimates and the test and demonstrate their use in statistical inference. Our results suggest that the chi-square distribution with 1.4 degrees of freedom provides a useful test criterion even when the sample sizes are as small as 10. Only in obvious testing situations is thet-test adequate.

ISSN:1054-3406    

DOI:10.1080/10543409308835049

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

A simulation study was conducted to compare the levels of significance and power between Schuirmann's and nonparametric two one-sided tests procedures for a 2 ×2 crossover design under different combinations of sample sizes, intrasubject variabilities, and underlying distributions. Empirical results suggest that Schuirmann's two one-sided tests procedure is robust to minor departure from the assumption of normality.

ISSN:1054-3406    

DOI:10.1080/10543409308835050

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

Design and analysis methods for the three-period crossover trial defined by the sequences:(D0D1D2), (D1D0D2), and (D1D2D0), whereD0is a placebo, andD1andD2are a low dose and a high dose of a drug, respectively, are developed. This design may be used when investigators are unwilling to administer a higher dose of a new drug to a patient before administering a lower dose. In using this design, patients should be randomized to sequences in blocks that are integer multiples of 3. Both parametric and non-parametric analysis methods are based on contrasts that capture in-trapatient variability only and provide unbiased estimates and hypothesis tests of pairwise differences between carryover, direct dose, and period effects. The design and methods are illustrated with data reflecting the cognitive component of the Alzheimer's disease assessment scale collected in a large clinical trial of Tacrine at doses of 0, 40, and 80 mg/day.

ISSN:1054-3406    

DOI:10.1080/10543409308835051

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

Subsampling can be used in experimental design to investigate extraneous sources of variability. One useful strategy is to make independent replicate measurements of the response variate. This can be achieved in clinical studies, for example,by dividing a blood or urine specimen from each of a sample of subjects into aliquots and processing these through a chemistry laboratory in such a way that the replicate determinations are independent. This procedure can be used to increase design efficiency. This paper addresses considerations in the design and analysis of the 2×2 crossover plan with this type of subsampling.

ISSN:1054-3406    

DOI:10.1080/10543409308835052

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

摘要:

Differential exposure to study medications in long-term studies of some cardiovascular compounds complicates analyses, particularly the usual intention-to-treat analyses and inferences therefrom of the data collected. Analysis methods that incorporate exposure are developed, presented, and illustrated by applying them to primary response data from a long-term, placebo-controlled, ancillary trial of gemfibrozil. The analysis methods address the extent to which end-points are correlated with the actual use of the compound rather than the extent to which end-points are correlated with the random assignment to double-blind study medications.

ISSN:1054-3406    

DOI:10.1080/10543409308835053

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409308835044

出版商:Marcel Dekker, Inc.    

年代:1993

数据来源: Taylor