摘要:

This paper deals with a method of sample size allocation for a dose-response study assuming a logistic model for the dose-response curve. The method is based on the precision with which one wishes to estimate the dose that would produce the efficacy resulting in a clinically important difference from a placebo. An example is given to illustrate the methodology. The main development of the paper is for a binary response and is suitably modified for a continuous variable.

ISSN:1054-3406    

DOI:10.1080/10543409208835027

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

Several statistical methods have been proposed or used in the determination of an increase in frequency of reports of adverse drug reactions. Some of the methods are based on large sample approximation or equal sample sizes assumption. The actual type I error may differ significantly from the predetermined nominal level of 5% when the methods are applied to rare adverse events. Simulated false alarm rates of the methods were compared under the assumption of 10 or less expected reports in the reference period.

ISSN:1054-3406    

DOI:10.1080/10543409208835028

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

Information theory is used to provide a measure of selectivity, i.e., the degree to which a drug has preferential toxicity or growth inhibition for one or a few cell lines from a large panel. The selectivity measure is intended to complement a measure of differential growth inhibition in evaluating the drug development potential of a new compound. Also, a similarity measure obtained from information theory is used to classify drugs according to their pattern of responses on the panel. Some structure-activity relations emerge. This work is applied to 176 agents selected to be tested by the National Cancer Institute in about 50 cell lines.

ISSN:1054-3406    

DOI:10.1080/10543409208835029

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

We consider the situation where a multiple-dose, combination-drug clinical trial is conducted to identify one or more combinations that satisfy regulatory requirements. Generally, these requirements involve a compound hypothesis with multiple comparisons. The min test has been shown to be an optimal α-level test for testing a single combination drug. Analysis procedures in a multiple-dose, combination-drug study have typically involved classical ANOVA models or multiple regression models in a response surface methodology (RSM) framework. An inferential procedure based on an ANOVA model uses a screening test to address multiple comparison issues and multiple min tests to explicitly identify combinations satisfying regulatory requirements. An exploratory procedure based on RSM modeling is used to build a segmented linear model and a stairstep linear model to describe dose-response relationships. The two procedures are mutually supportive of one another in providing a broader assurance in the identification of effective combinations.

ISSN:1054-3406    

DOI:10.1080/10543409208835030

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

Two methods of estimating expiration date have been compared. For a drug whose potency is expected to decrease with time, method 1 fits a linear regression line to the stability data, calculates a 95% lower confidence limit of the true degradation line, and estimates the expiration date by comparing the confidence limit with the lower specification limit. Method 2 calculates a 95% lower confidence limitb1of the slope of the true degradation line, constructs a new line y” usingb1as its slope, and finally estimates the expiration date by comparing y” with the lower specification limit. In this work we show that in most practical situations, method 1 estimates greater expiration date than method 2.

ISSN:1054-3406    

DOI:10.1080/10543409208835031

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

While a large portion of pharmaceutical stability data is known to follow an exponential model decay, linear modeling of this data for expiry estimation is the norm. Expiry predictions based on linear and exponential fits to stability data were made to estimate the bias due to the linear fitting. It was found that within the usual expiry limits on drug potency, the difference between the model fits is relatively trivial. In cases of loss of potency greater than 15%, small assay variability, or great disparity between the length of the study and the time of expiry prediction, however, there is a nontrivial difference in the predictions and the exponential model is preferable.

ISSN:1054-3406    

DOI:10.1080/10543409208835032

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

Studies are routinely conducted during development of a new drug to investigate the effect of strength, package, batch, storage condition, and storage time on stability of the dosage form. A typical study will have three batches, several strengths, several packages, and several storage conditions. Thus, if every batch by strength by package combination is tested for every storage condition, i.e., if a complete factorial design is used, a substantial expense is involved. To reduce expense, a matrix design is commonly used; e.g., only the smallest and largest bottles are tested. Fractional factorial—type designs for stability studies are proposed, and the statistical powers of various designs are compared.

ISSN:1054-3406    

DOI:10.1080/10543409208835033

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

摘要:

A computer pattern recognition system, RAPID, has been used to study the spontaneous motor activity of Sprague-Dawley rats. This system produces a large number of measures of the activity of control and experimental groups in any given study. The large number of measures involved presents a problem when one attempts to decide whether the behavioral activity of the exposed group differs from that of the control group. Extensive Monte Carlo studies have been performed in an attempt to develop and validate a simple statistic to be used in such decisions.

ISSN:1054-3406    

DOI:10.1080/10543409208835034

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409208835026

出版商:Marcel Dekker, Inc.    

年代:1992

数据来源: Taylor