摘要:

An estimation procedure has been developed for the estimation of parameters from bulked samples using the parametric bootstrap and density estimation in conjunction with the one-step maximum-likelihood estimator. It is shown that the proposed estimation procedure provides an asymptotically efficient estimator for parameters of interest when the density for the mean of the bulked samples has a certain form. The lognormal density (with σ2assumed known) is an important distribution with the proper form. The finite sample performance for bulked samples based on underlying lognormal observations was examined by Monte Carlo study. The results indicate that the proposed procedure leads to a reduction in mean squared error compared to known procedures.

ISSN:1054-3406    

DOI:10.1080/10543409108835002

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

Nonparametric tests of group differences and interaction across strata are developed in which the null hypotheses for these tests are expressed as functions of, whereXrefers to a random observation from one group andYrefers to a random observation from the other group within stratumi. The estimatorrof the parameter ρ is shown to be a useful way to summarize and examine data for ordinal and continuous data.

ISSN:1054-3406    

DOI:10.1080/10543409108835003

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

An ability to predict the metabolic fate of a drug is important to drug design. Programs for predicting drug metabolites are becoming available, as are databases that will facilitate the development of such programs. Objective analysis of the performance of these programs will require statistical methods. The development of appropriate statistical methods must address a fundamental data representation problem that arises from the fact that the basic metabolic information uses chemical graph representations rather than the usual vector representations that typify statistical methodology. This study addresses the representation problem by using concepts arising from molecular similarity analysis. The statistical methods that are developed are illustrated by evaluating the performance of MetabolExpert in predicting the metabolic fate of benzodiazepines.

ISSN:1054-3406    

DOI:10.1080/10543409108835004

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

On the basis of calculated cumulative hazard rates for initial occurrence of adverse experiences of patients following treatment for rheumatoid arthritis and osteoarthritis, a simple function is evolved that fits such cumulative hazard rate data very well. From this simple function, we obtain the estimated hazard rate in terms of two physically meaningful parameters. These two parameters can be used to describe the rate of occurrence of adverse experiences, and to convey the concept of risk of adverse experience associated with duration of exposure to a drug.

ISSN:1054-3406    

DOI:10.1080/10543409108835005

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

One of the criteria for demonstrating efficacy in a single multicenter trial is that the centers are consistent with respect to the direction and significance of results. The purpose of this research is to discuss the use of the noncentrality parameter δ of anFdistribution as a means of testing for the consistency of treatment effects across centers. We state the testing problem asH0{δ > δ0} versusH1: {δ ≤ δ0}, where δ0is prespecified, so thatH0represents inconsistency andH1consistency. Thus, strong evidence from the sample data is required in order to conclude that the treatment effects are consistent across centers. We discuss reasonable choices for δ0and develop the α-level, uniforrmly most powerful and unbiased test, which is equivalent to rejectingH0if the 100(1 – α)% uniformly most accurate and unbiased upper confidence limit for δ is less than or equal to δ0. We examine other tests based on upper confidence limits, such as those calculated from linear estimators of δ and those calculated from a likelihood approach. We investigate the performance of the tests in a small simulation study and present an example from a four-center clinical trial.

ISSN:1054-3406    

DOI:10.1080/10543409108835006

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

The Bayesian approach to inference and decision making provides an integrated way of addressing the various aspects of drug development, from the early preclinical study of compounds through the clinical and postmarketing phases. In particular, it provides a natural, convenient way for choosing among experimental designs. An essential aspect of the process of evaluating design strategies is the ability to calculate predictive probabilities of potential results. I describe a Bayesian approach to experimental design and illustrate it by considering a particular type of clinical trial. Also, I compare Bayesian and classical statistical attitudes toward design.

ISSN:1054-3406    

DOI:10.1080/10543409108835007

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

A meta-analysis is a statistical analysis of the data from some collection of studies in order to synthesize the results. In this paper we discuss issues that frequently arise in meta-analysis and give an overview of the methods used, with particular attention to the use of fixed- and random-effects approaches. The methods are then applied to two sample datasets.

ISSN:1054-3406    

DOI:10.1080/10543409108835008

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

When new drugs are developed for indications where no effective therapies have been established, such as emphysema, useful measures of clinical activity have to be derived from a large number of proposed measures. It often happens that most of the proposed measures are of little use in tracking the disease and that the numbers of patients needed to establish whether the drug is effective is very large. Thus, the first study in man may be the size of the usual Phase III “confirmatory” study, and the expense and the time needed to complete it are so great that decisions about the future development of the drug will depend upon this one large study. The situation of such innovative therapies is examined, and methods for controlling the error rate when almost ail analyses have to be exploratory are proposed.

ISSN:1054-3406    

DOI:10.1080/10543409108835009

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

Whether a one-sided or a two-sided ρ value should be used for reporting the results of an analysis should be determined by thea prioriquestion the investigation seeks to answer. It is concluded that one-sided ρ values are appropriate in clinical trials whose objective is to provide definitive, confirmatory evidence of efficacy of pharmaceutical compounds.

ISSN:1054-3406    

DOI:10.1080/10543409108835010

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor

摘要:

This paper addresses some scientific and regulatory perspectives, insightful regulatory experiences, academic views, and current practices pertinent to one-sided and two-sided tests within the framework of clinical trials designed for specific diseases and drugs. It makes compelling points in favor of applying a two-sided test under a wide variety of situations. Additionally, it discusses situations where one may reasonably argue for use of a one-sided test and concludes by suggesting the use of two-sided tests in controversial situations.

ISSN:1054-3406    

DOI:10.1080/10543409108835011

出版商:Marcel Dekker, Inc.    

年代:1991

数据来源: Taylor