摘要:

AbstractIn cancer studies, the aim of phase I clinical trials is to identify an appropriate dose for experimentation in phase II and III studies. The continual reassessment method (CRM) has been developed recently and presented as the method of choice in the design and analysis of such phase I studies. However, to implement the method, some methodological and practical considerations must be addressed. This paper examines, through a simulation study, the sensitivity of CRM both to the initial modelling of the dose‐toxicity relationship and the prior. It appears that the performance of CRM can be improved by using vague priors and initial tuning of the model to allow flexibilit

ISSN:0277-6715    

DOI:10.1002/sim.4780121201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIn a traditional assessment of the bioequivalence of two formulations of a drug one compares the average bioavailability from the two formulations. Anderson and Hauck argued that in some situations it is not sufficient to demonstrate average bioequivalence, and they proposed a method for the assessment of what they called individual bioequivalence, which essentially is the comparison of the individual responses to the two drug formulations within subjects. In this paper we propose a unified strategy for the assessment of bioequivalence that encompasses new approaches to the assessment of both population bioequivalence, which is the comparison of the marginal or population distributions of bioavailabilities, and individual bioequivalence, which is the comparison of the conditional or within‐subject distributions of bioavailabilities. The general idea is to use a comparison of the reference formulation to itself as the basis for the comparison of the test with the reference formulation. The new approaches overcome the main weakness of the current methods for the assessment of bioequivalence by considering the variability of bioavailabilities in addition to their means. The current methods for the assessment of bioequivalence, namely the conventional assessment of average bioequivalence and the proposal by Anderson and Hauck for the assessment of individual bioequivalence, emerge as special cases. One can evaluate the new bioequivalence criteria statistically by use of bootstrap confidence interval

ISSN:0277-6715    

DOI:10.1002/sim.4780121202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIn comparing running median, tolerance, cusum, and regression methods for trend detection over a small number of visits, Yanget al.found that application of multipleZ‐tests on the basis of a simple linear regression for each site separately was the most efficient for detection of trends at several sites simultaneously. Because the use of multipleZ‐tests completely ignores the covariance among measurements taken from different sites, to improve the power we propose a global χ2‐test. Assuming the covariance matrix known, we have found that the proposed χ2‐test procedure is more powerful than multipleZ‐tests for two‐sided alternatives when both the correlation among measurements and the number of sites are small. We also have found that the former procedure can have power uniformly larger than the latter when ratios of slopes to standard deviations of measurements at different sites vary and the number of sites is large. In fact, in the latter situation, the proposed global χ2‐test procedure, usually used only for two‐sided alternatives, can even have power larger than that of multipleZ‐tests for one‐sided alternatives. In the situation where the ratios of slopes to standard deviations of measurements are all equal, however, the proposed multivariate approach based on the χ2‐test distribution is the least efficient, especially when the number of sites and the correlation are moderate or large. Finally, to account for the effect of multiple tests over a series of visits on the overall α‐level, on the basis of Monte Carlo simulations, we compute critical values for sequential use of the proposed

ISSN:0277-6715    

DOI:10.1002/sim.4780121203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractTo estimate the parameters in a logistic regression model when the predictors are subject to random or systematic measurement error, we take a Bayesian approach and average the true logistic probability over the conditional posterior distribution of the true value of the predictor given its observed value. We allow this posterior distribution to consist of a mixture when the measurement error distribution changes form with observed exposure. We apply the method to study the risk of alcohol consumption on breast cancer using the Nurses Health Study data. We estimate measurement error from a small subsample where we compare true with reported consumption. Some of the self‐reported non‐drinkers truly do not drink. The resulting risk estimates differ sharply from those computed by standard logistic regression that ignores measurement er

ISSN:0277-6715    

DOI:10.1002/sim.4780121204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractCoronary occlusive disease following cardiac transplantation is monitored using serial angiography, and graded on a 3 point scale according to the amount of narrowing observed in major vessels. Disease progression is modelled as a continuous time Markov process. The Gibbs sampler is used to estimate the marginal posterior distributions of the transition rates between grades of disease and from each grade to death.

ISSN:0277-6715    

DOI:10.1002/sim.4780121205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThis paper describes the Stoke Index which has been designed to give a global measure of disease activity in rheumatoid arthritis. The index is based on two objective laboratory measurements, one subjective and two semi‐objective clinical measurements, chosen from 13 measurements using clinical judgement. Variable selection routines in principal components analysis are used to demonstrate that the index measures clinically defined disease activity. Its sensitivity and reversibility are also considered. A comparison is carried out with another index (Mallya‐Mace) and a modification is sugges

ISSN:0277-6715    

DOI:10.1002/sim.4780121206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

ISSN:0277-6715    

DOI:10.1002/sim.4780121207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY