摘要:

In Tamhane Hochberg, and Dunnett (1) we focused primarily on step-down test procedures based on contrasts among the sample means to find the minimum effective dose in a dose-response study. In the present article we use the global tests of Bartholomew (2,3) and Hayter (4) in these step-down procedures. We also propose a new step-down procedure that permits tests based on a class of contrasts [step and basin contrasts of Ruberg (5) are examples of such contrasts] that could not be used with the step-down procedures studied in our previous paper because of lack of control of the familywise error rate. A simulation study to compare the four procedures proposed in the present paper with the top four procedures from the previous article is carried out. It is found that the step-down procedure based on Bartholomew's test and the new step-down procedure based on step and modified basin contrasts generally perform better than the other procedures for a wide range of dose-response profiles.

ISSN:1054-3406    

DOI:10.1080/10543409808835245

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

In many clinical trials, the primary endpoint is dichotomous. In this article, we examine the possibility of reducing the required sample size by removing variation associated with baseline covariables. Three measures are used to study the size of the reduction. Simulation studies based on a database of head trauma and of stroke patients suggested that a substantial reduction in the sample size can be achieved when the correlation between the endpoint and covariables is strong. A simple ad hoc formula for approximating the required sample size is proposed.

ISSN:1054-3406    

DOI:10.1080/10543409808835246

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

Clinical equivalence has almost exclusively been treated from the view of average equivalence. However, as in bioequivalence there has been recent interest in more general definitions of clinical equivalence. In particular, Bauer and Bauer (1) have investigated the possibility of the use of a pair of tests for the equality of means and variances taking account of the multiplicity issues involved. In bioequivalence a number of authors have considered a Bayesian approach; in this article we generalize these previous Bayesian approaches to this more general problem. We investigate the operating characteristics of a decision procedure based on the posterior probability that the parameters lie within a prespecified region of equivalence.

ISSN:1054-3406    

DOI:10.1080/10543409808835247

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

A common method of choosing the link function in generalized linear models is to specify a parametric link family indexed by unknown parameters. The maximum likelihood estimates of such link parameters, however, may often depend on one or several extreme observations. Diagnostics are derived to assess the sensitivity of the parametric link analysis. Two examples demonstrate that the proposed diagnostics can identify jointly influential observations on the link even when masking is present.

ISSN:1054-3406    

DOI:10.1080/10543409808835248

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

It has become common to collect blood samples from patients for phase II/III clinical trials to investigate pharmacokinetic/pharmacodynamic relationships. However, the frequency of blood samples drawn from patients is limited due to clinical or pharmacoeconomic reasons.

ISSN:1054-3406    

DOI:10.1080/10543409808835249

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

The study of protein-construct activity provides valuable insight in the early stages of drug discovery. Identification of optimal storage conditions that maintain activity of the constructs is an important issue. In the study reported herein, a space-filling design was used to assess the effects of eight design variables—buffer, pH, NaCl, protein concentration reducing agent detergent, MgCl2, and temperature—on protein activity. A regression spline analysis is presented and settings of the explanatory factors resulting in the best predicted protein activity over the explored space are identified. The models are selected initially based on the Akaike information criterion and later assessed via root mean square error and cross-validation root mean square error. Detergent, buffer, temperature, and smooth functions of pH and protein concentration were found to have large effects on protein activity. The models were calibrated via calculation of the empirical distribution of the cross-validation root mean square error. In this framework several models provide a similar fit, and further experimentation is required for more definitive conclusions re- garding protein storage conditions to be made. The cross-validation root mean square error calibration of models is recommended for applications involving comparisons of models with respect to their predictive ability.

ISSN:1054-3406    

DOI:10.1080/10543409808835250

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

Determining optimal conditions for protein storage while maintaining a high level of protein activity is an important question in pharmaceutical research. A designed experiment based on a space-filling design was con- ducted to understand the effects of factors affecting protein storage and to establish optimal storage conditions. Different model-selection strategies to identify important factors may lead to very different answers about optimal conditions. Uncertainty about which factors are important, or model uncertainty, can be a critical issue in decision-making. We use Bayesian variable selection methods for linear models to identify important variables in the protein storage data, while accounting for model uncertainty. We also use the Bayesian framework to build predictions based on a large family of models, rather than an individual model, and to evaluate the probability that certain candidate storage conditions are optimal.

ISSN:1054-3406    

DOI:10.1080/10543409808835251

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

Early-phase clinical trials, conducted to determine the appropriate dose of an experimental drug to take forward to later trials, are considered. The objective is to find the dose associated with some low probability of an adverse event. A Bayesian model is presented, and a decision-theoretic procedure for finding the optimal doses for each of a series of cohorts of subjects is derived. The procedure is flexible and can easily be conducted using standard statistical software. The results of simulations investigating the properties of the procedure are presented.

ISSN:1054-3406    

DOI:10.1080/10543409808835252

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

There is no consensus on determination of sample size in phase II clinical trials. The use of Bayesian decision theory has been proposed by Stallard (1), among others. In this article, optimal three-stage designs are obtained using decision theory. These are compared with procedures proposed by Schoenfeld (2), Ensign et al. (3), and Chen et al. (4) and the sequential probability ratio test of Wald (5) and Barnard (6). The three-stage procedures are shown to be close to the true optimal test; the sequential probability ratio test is easier to obtain and only marginally inferior.

ISSN:1054-3406    

DOI:10.1080/10543409808835253

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor

摘要:

Assume that in a comparative clinical study the primary endpoint is a binary event, such as life or death. A new treatment or therapy is tested for a significant reduction of the incidence of the binary event compared with a control group. Another objective is to ensure that the incidence in the new treatment group is below some clinically acceptable value. This is done by calculating the exact upper 95% confidence limit for the probability of the event. The study is considered successful if the upper confidence limit is lower than a historical threshold, as well as if there is a significant reduction in the incidence of the event by the new treatment. In this article, we provide an exact method for calculating the sample size so that there will be adequate power to ensure that the exact upper confidence limit is below the threshold. Based on this we can design a study to achieve both objectives.

ISSN:1054-3406    

DOI:10.1080/10543409808835254

出版商:Marcel Dekker, Inc.    

年代:1998

数据来源: Taylor