摘要:

We develop a statistical methodology for the assessment of individual bioequivalence when a crossover design is invoked. The location parameters for our model consist of population-averaged parameters for formulation, population-averaged parameters for nuisance effects (sequence, period, carryover, etc.), and subject-specific parameters for formulation. We do not impose any distributional assumptions other than the existence of first- and second-order moments. We derive unbiased estimators for all of the parameters in the model and construct subject-specific bioequivalence scores which exclude the effects of the nuisance parameters. We assess individual bioequivalence by constructing distribution-free tolerance intervals based on the sample of bioequivalence scores.

ISSN:1054-3406    

DOI:10.1080/10543409608835118

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

In clinical trials and behavioral sciences, there exist situations where paired responses are obtained from each subject on an ordinal scale. Existing methods for analyzing such data in a factorial design are reviewed and new methods are developed with a special emphasis on pre-and post-treatment responses. The distribution of a square table is decomposed into successively independent pairs of discordant vectors, and assuming a logistic model, a statistics is computed to measure the shift in the marginal distributions. The approach is similar to McCullagh's approach (1). Two other criteria are proposed, one based on a Lehmann alternative used for comparing two distribution functions and the other based on a proportional odds model. These criteria are applied to the marginal distributions of a square table. For each case, a statistic measuring lack of marginal homogeneity and its variance are computed for each independent square table of a factorial design. Given such statistics, one can estimate a set of linear contrasts and compute its dispersion matrix for making inference. A numerical example is given.

ISSN:1054-3406    

DOI:10.1080/10543409608835119

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

In recent years, the assessment of drug effects on quality of life (QOL) has become very popular in clinical trials. QOL assessment quantifies the ability of a person to function normally in society. It may be used to distinguish between therapies that appear to be equally efficacious and equally safe. QOL is usually assessed by a QOL instrument, which consists of a number of questions. A QOL instrument is a very subjective tool that usually has a large variation. To ensure the accuracy and reliability of QOL assessment in clinical trials, the adopted QOL instrument should be validated. Some statistical tests are proposed for validation of a QOL instrument in terms of validity, reliability, test-retest reproducibility, responsiveness, and sensitivity. Some statistical issues regarding the validation of utility analysis and calibration for QOL against life events and /or disease status will also be discussed.

ISSN:1054-3406    

DOI:10.1080/10543409608835120

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

A method of stratifying the data according to the patterns of missing observations, summarizing each subject's repeated measurements by a summary measure and then comparing the treatment groups with the help of a distribution-free test based on the summary measure, is used here to compare the efficacy of tacrine dose regimens with that of placebo in a recent trial in Alzheimer's disease patients. The usefulness of the method of meta-analysis for comparing the treatment groups, in the presence of missing data, is also investigated.

ISSN:1054-3406    

DOI:10.1080/10543409608835121

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

Mixed-model techniques are applied to incomplete longitudinal data from a double-blind, placebo-controlled, parallel-group, high-dose study of tacrine in patients with Alzheimer's disease. The study consisted of a 30-week double-blind treatment period. Patients were randomized to one of four treatment groups. Dosing was initiated at 40 mg/day and increased in increments of 40 mg/day every 6 weeks until the target dose was achieved. If the study medication was not well tolerated or there were significant elevations in alanine aminotransferase, patients were withdrawn from the study. The use of SAS procedure PROC MIXED for the analysis of incomplete longitudinal data is discussed. This approach is used to evaluate disease progression over time and the effect of incremental dose increases of tacrine on changes on the Alzheimer's Disease Assessment Scale-Cognitive subscale.

ISSN:1054-3406    

DOI:10.1080/10543409608835122

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

Failure to recognize the serious implications of heterogeneous correlations and disregard of the multiple test problem in interpreting the results from repeated measurements ANOVA of any single primary outcome measure can produce false-positive error rates that are more than five times the alpha level that is reported. Alternative analyses that do not depend on the symmetry assumption, together with a Bonferroni correction of the multiple tests of significance that are routinely accomplished by the repeated measurements ANOVA, appropriately control the probability of statistical support for a false-positive claim. The magnitudes of error inflation and appropriate procedures for error control are examined in this article using simulated clinical trials data.

ISSN:1054-3406    

DOI:10.1080/10543409608835123

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

Clinical studies investigate the interdependence of dosing regimen, efficacy, and side effects. These relationships often involve complex dynamical functions. The study of phenomena intermediate between dosing and efficacy, e.g., pharmacokinetics (PK), helps one identify and understand these interdependences. However, efficacy still tends to be a complicated function of PK parameters, and indeed these parameters are becoming more complex as a function of dosing regimen, viz., studies involving immunosuppressants, biotechnology drugs, sophisticated delivery systems, and dosing strategies. Stationary and time-dependent neural nets can help one identify and model such unknown complex dynamical functions with few assumptions and limited data (1-7). Neural nets can relate dosing directly to efficacy, dosing to PK,PK to efficacy, or any component in the complex associations among treatments, pharmacodynamics, efficacy, and side effects. Neural nets can also assist one in the design of clinical trials involving complex and sophisticated procedures, e.g., randomized controlled clinical trials.

ISSN:1054-3406    

DOI:10.1080/10543409608835124

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

摘要:

Given a set of measurements on a patient in clinical studies or on a drug response in bioassays and immunoassays, the data series for the individual can be incomplete, noisy, and haphazard. Hence, meaningful analysis on such limited data is at best difficult given the typical assumptions on the nonlinear structure of systematic and random components involving both individual and population effects. This paper describes a simple direct semiparametric procedure to incorporate population-wide information from as many individuals as required to support analysis of data on any specific individual. This notion is motivated by the pattern-processing capabilities of experts as they evaluate data on an individual based on their reservoir of accumulated knowledge of the given application on many individuals.

ISSN:1054-3406    

DOI:10.1080/10543409608835125

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor

ISSN:1054-3406    

DOI:10.1080/10543409608835117

出版商:Marcel Dekker, Inc.    

年代:1996

数据来源: Taylor