摘要:

AbstractIn some clinical trials one can employ adaptive designs advantageously, although in practice such techniques are rarely used, in part due to their inherent complexity. A simple and practicable decision‐theoretic approach for the case of three treatments with binary responses is considered, using equal allocation to remaining treatments and, once eliminated, a treatment cannot be re‐employed. Having specified the overall number of patients treated within and beyond the comparative stages of the trial, the goal is to maximize the expected total number of those successfully treated. Investigation of the method involves a computer program that can handle arbitrarily large numbers of patients. It is shown empirically that the decision procedure behaves only marginally worse than if the truly superior treatment had been known and had been given to all patients. Implementation of the method uses a minimax approach that removes dependence on prior parameters. Primarily an identification procedure, one advantage of this approach over traditional hypothesis testing methods is the potential to detect small improvements in treatment efficacy. The intended application is to assist in treatment selection during phase II trials, especially with rapid responses and when the disease involved is serious enough that design‐motivating ethical considerations become para

ISSN:0277-6715    

DOI:10.1002/sim.4780100902

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

年代:1991

数据来源: WILEY

摘要:

AbstractIn clinical trials there is delay between the occurrence of an event and the recording of that event as an end point in the trial data base. Delays are especially likely if events are reviewed carefully to determine whether diagnostic criteria for end points are satisfied. As a result, the value of a a statistic used to evaluate efficacy during a trial may differ from the value of that statistic based on the true end point status of all events which have already occurred. Simulating the process causing delays can be useful in evaluating interim efficacy data by providing a quantitative estimate of the uncertainty in a monitoring statistic. These ideas are illustrated using data from the Lipid Research Clinics Coronary Primary Prevention Trial.

ISSN:0277-6715    

DOI:10.1002/sim.4780100903

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

年代:1991

数据来源: WILEY

摘要:

AbstractRandomized clinical trials are typically conducted to compare the efficacy (benefits) and side effects (risks) of two or more treatments. One can use results from such trials to decide on a preferable treatment that reflects one's own evaluation of the benefits and risks. To facilitate the necessary decision making, we propose in this paper three measures for simultaneously assessing benefits and risks. All three measures use weights that reflect the relative importance of the various treatment outcomes to an individual. Two of them carry the flavour of benefit/risk ratios, while the third generalizes Hilden's measure which incorporates patients' preferences. The proposed measures and procedures are illustrated using data from a phase III clinical trial of antihypertensive compounds.

ISSN:0277-6715    

DOI:10.1002/sim.4780100904

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe problem of carryover in crossover trials has received a great deal of attention in the statistical literature. Carryover is just one form of period by treatment interaction; yet a parallel problem of patient by treatment interaction, which may be regarded as dual to that of carryover, has received little attention. We suggest that the phenomenon of patient by treatment interaction requires a repeated measures approach to the analysis of crossover trials. A simple solution using predefined contrasts is presented and illustrated by example.

ISSN:0277-6715    

DOI:10.1002/sim.4780100905

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

年代:1991

数据来源: WILEY

摘要:

AbstractThis paper considers the problem of detecting outlying data in bioavailability/bioequivalence studies. We define outlying subjects as those whose responses in bioavailability to all formulations differ from the rest of the subjects. We also define an outlying observation as the response in bioavailability of a subject to a particular formulation which is grossly different from the average bioavailability of that formulation calculated from all subjects. We propose two test procedures. The first, based on two‐sample HotellingT2, is to detect possible outlying subjects. The second, based on residuals from formulation means, is to identify possible outlying observations within subjects. Both procedures take into account the covariance structure of the responses to formulations, dependence of test statistics, and multiplicity of test procedures. We apply the Monte Carlo or bootstrap simulation to evaluate the sampling distributions of test statistics. An example from a 3‐way crossover bioequivalence study illustrates the two procedu

ISSN:0277-6715    

DOI:10.1002/sim.4780100906

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe multivariate probit model is designed to regress a vector of correlated quantal variables on a mixture of continuous and discrete predictors. Various applications can be found in the biological, economical and psychosociological literature, but the method is not yet widely used in medical applications. We reintroduce this model thereby showing its usefulness in medical problems. Software for this model is, however, not widely available. We have written a PC program to select predictors and estimate parameters in the multivariate probit framework. The performance and characteristics of the program are briefly illustrated.

ISSN:0277-6715    

DOI:10.1002/sim.4780100907

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe consider methods for selecting the joint specification of the mean and variance functions in statistical models for rates or counts. Based on analyses of diagnosis‐specific hospital discharge rates in Michigan, we show that a Poisson model with an extra variance component for the systematic variation is superior to several other probability models with regard to specification of the error structure. Further, the deviance residual appears superior to the Pearson residual. The proper specification of such variation is crucial for many types of analyses, such as identification of outliers and regression analyses designed to explain the systematic component of the variatio

ISSN:0277-6715    

DOI:10.1002/sim.4780100908

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

年代:1991

数据来源: WILEY

摘要:

AbstractThis paper develops a method for estimating the odds ratio in a case‐control study that ‘borrows’ strength from the controls in similar previous studies. We assume that the observations within each stratum in the current study are generated from a pair of independent binomial distributions. We assume that the observations on the controls, again within each stratum and from the previous studies, are independent binomial random variables. We use these controls to construct a prior distribution for the stratum specific log‐odds for the controls in the current study which we then combine with the likelihood from the current study to arrive at the posterior distribution of the target quantities of interest, the adjusted or stratum specific log‐odds ratios. We assume a diffuse prior distribution for the stratum specific log‐odds ratio. A simulation study investigates the frequency or repeated sampling properties of the inference based upon the posterior distribution of the log‐odds ratio s

ISSN:0277-6715    

DOI:10.1002/sim.4780100909

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe designed and implemented stochastic methods for short term projections of HIV disease at the local level, that accommodate various states or stages of the disease. We gave particular attention to projection of the number of patients with HIV disease who need care, when durations of stay in these various states depend on current methods for treating opportunistic infections. We consider two types of data as input to these projections. One concerns seroprevalence surveys conducted over time and from which we can obtain time series estimates of the numbers of HIV‐infected individuals. The other is a reported time series of AIDS cases adjusted for delays in reporting. Several projections, with data from the City of Philadelphia, illustrate this method. In addition, we consider a Monte Carlo method for computing confidence bounds on a projectio

ISSN:0277-6715    

DOI:10.1002/sim.4780100910

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

年代:1991

数据来源: WILEY

摘要:

AbstractIdeally, the basis for estimation of variance components is large random samples selected from a well‐defined reference population. Some large biomedical studies, however, consist of a random sample (S) of individuals ascertained at an initial visit, with a selected subsample fromSseen on one or more follow‐up visits. In this setting, the usual formulae for estimation of variance components are problematic since they do not take into account the censored nature of the data. For this purpose, we consider both maximum likelihood and moments estimation methods that take the censoring into account, and we compare their performance, in terms of bias and mean squared error, with that of the usual variance components estimators that ignore censoring. We find the maximum likelihood estimators somewhat more efficient than method of moments estimators, provided that the assumption of multivariate normality is met; furthermore, these estimators are substantially more efficient than those that ignore the censoring. It is important to record data on all individuals, even those who do not meet screening criteria; one can estimate between‐ and within‐person variance more accurately with use of all available data. The resulting estimates are crucial in calculation of power for the design of future

ISSN:0277-6715    

DOI:10.1002/sim.4780100911

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

年代:1991

数据来源: WILEY