摘要:

As part of an application for licensure of a new drug, it is necessary to provide data on the stability of the product over time under various conditions. If every combination of conditions is studied at every sampling time, the cost of the study can be substantial. To minimize expense, matrix designs are discussed, whereby only a fraction of the various design combinations of interest are tested at any specified sampling time. A method for choosing the time vectors such that the design is optimal in terms of maximum information per unit cost is proposed.

ISSN:1054-3406    

DOI:10.1080/10543409708835181

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

The basis of sample size calculations is usually needed in protocols for clinical trials and when publishing results in respected journals. Although a large amount of research has been undertaken on sample size estimation for different

ISSN:1054-3406    

DOI:10.1080/10543409708835182

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

The cumulative sum (CUSUM) technique is applied to monitor spontaneous reports of adverse drug reactions (ADRs). The beta-binomial model, as suggested by Moussa (2), was used to fit the observed proportion of upper gastrointestinal perforation, and ulcer (UGIBPU) for drug A, a nonsteroidal anti-inflammatory drug (NSAID). ADRs reported directly by physicians and manufacturers from the third quarter of 1982 through the fourth quarter of 1985 were analyzed. The model estimates the proportion of UGIBPUs for drug A expressed as a fraction of all UGIBPUs for NSAIDs. To illustrate the procedure, estimated mean proportion of UGIBPUs for drug A and all NSAIDs was computed for directly reported physician and manufacturer ADRs. The beta-binomial

ISSN:1054-3406    

DOI:10.1080/10543409708835183

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

The problem for assessment of similarity between dissolution profiles of two drug products is considered. The commonly used classical methods including model-dependent and model-independent approaches are reviewed. Most methods encountered the difficulties of no well-defined equivalence limits and the correlation between consecutive time points. Several methods have been proposed to account for these difficulties e.g., the method of repeated measures (1) and the multivariate analysis approach (2). These methods, however, are sensitive to the selection of time points and complex covariance error structure. In this paper we propose equivalence limits for similarity based on the amount of dissolved active ingredient as specified in the United States Pharmacopeia and National Formulary (USP/NF). Accordingly, we proposed a time series approach, which accounts for correlation between dissolution results at different time points. The proposed model is shown to be useful in assessment of similarity between dissolution profiles of two drug products. An example concerning dissolution testing of two lots of a drug product is used to illustrate the proposed equivalence limits and statistical methodology.

ISSN:1054-3406    

DOI:10.1080/10543409708835184

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

In dissolution testing, multiple dissolution measurements at specific time points are used to obtain the dissolution characteristics for most extended- release and some immediate-release drug products. This paper presents a general procedure for defining specifications by a multivariate confidence region or by simultaneous confidence limits on the dissolution values of individual time points. The confidence regions and simultaneous confidence limits were estimated using two approaches: the first approach assumed a multivariate normal distribution on the multiple dissolution values and the second approach used the bootstrap resampling method. The multivariate confidence region was constructed using the Hotelling'sT2statistic (equivalently, Mahalanobis distanceD2), and the simultaneous confidence limits were based on the Mahalanobis statistic as well as on the Bonferroni adjustment. The Mahalanobis simultaneous confidence limits specification criteria have the overall false out-of-specification rate too low in both parametric and bootstrap approaches.

ISSN:1054-3406    

DOI:10.1080/10543409708835185

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

Consider the situation in which there are several different therapeutic agents. It is desired to select the best agent and to examine its efficacy relative to the control. Too often clinical trials terminate with negative outcomes in part due to inadequate phase II studies. A two-stage phase II based on a Bayesian approach is considered in order to reduce such likelihood. The first stage consists of selecting the best agent and the second stage consists of examining the relative efficacy of the selected agent compared to the control. A formal phase III clinical trial can be initiated when the particular agent is shown to be promising on the basis of the proposed phase II study. The Bayesian approach employed uses anad hoclikelihood due to the fact that the exact likelihood is complex and intractable. In this sense the proposed approach is thus an approximation. A simulation study is conducted to investigate the performance of the proposed Bayesian approach and compared to two fixed sample-size approaches. Due to the fact that the procedure is approximate, the simulation study is essential to assess the usefulness of the procedure. The study suggests that the Bayesian approach is an attractive alternative to fixed-sample-size approaches.

ISSN:1054-3406    

DOI:10.1080/10543409708835186

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

A statisticW, for measuring change from baseline is developed. Its distribution is found. Simulations usingWand analysis of covariance (ANCOVA) are run and the results are compared.Wis found to be less powerful than ANCOVA, yet is not seen to suffer some of the ill effects to which ANCOVA can fall prey namely bias introduced by chance covariate imbalance.

ISSN:1054-3406    

DOI:10.1080/10543409708835187

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

This paper presents a model-based assessment of the relationship between the dose of a test treatment and response. The data set used in the analysis describes the results of two clinical trials that were designed to assess the dose-response relationship of a test treatment. The models described in the paper are fit using weighted regression as implemented by the SAS procedure CATMOD. Relationships between weighted regression and other similar procedures are discussed.

ISSN:1054-3406    

DOI:10.1080/10543409708835188

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

摘要:

The analysis of data from clinical trials often includes subgroup analyses, which are performed to examine the treatment effect within various sets of patients based on baseline and/or demographic variables. The goals of these analyses are to establish the consistency of the results across the subgroups and to identify important prognostic factors. Thep-values for such analyses are usually presented without any adjustment for the multiple analyses. This approach has been criticized because of the possibility of misleading false positives. Conservative approaches have been proposed to resolve this problem; however, these approaches are usually so conservative that significant results are rarely observed after adjustment. Here an approximate technique for use when the variable of interest has a normal distribution is presented.

ISSN:1054-3406    

DOI:10.1080/10543409708835189

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409708835190

出版商:Marcel Dekker, Inc.    

年代:1997

数据来源: Taylor