摘要:

AbstractStopping guidelines are widely used in long‐term clinical trials involving two treatments. These allow planned interim analyses of the accumulating data to be undertaken whilst preserving the type I error rate for the treatment comparison. Their philosophy is extended to the case of trials with multiple treatments so that at any interim analysis, treatments may be considered for dropping from the trial if they are significantly inferior to all treatments that will remain. The proposed guidelines are designed to preserve the error rate in determining that treatment or group of treatments which is, in reality, best. Using simulation studies, stopping guidelines developed for two‐arm trials are shown to be directly usable in multiple‐arm studies when the treatments studied are all experimental and so in direct competition. When one treatment is the standard of care, a modification gives a better ethical perspective by also permitting treatments to be dropped when they are deemed inferior to the standard. Results are presented for normally distributed responses in trials involving three or four treatments and using stopping boundaries of the form proposed by O'Brien and Fleming. In conclusion, I discuss some of the additional considerations that are important in employing stopping guidelines in trials with multiple treat

ISSN:0277-6715    

DOI:10.1002/sim.4780121002

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis paper proposes a simple approach to the parametric derivation of age‐related reference ranges which avoids the creation of arbitrary age groups, copes easily with a non‐linear relation between variability and age, and is computationally simple. After the mean is modelled as a function of age, the age‐specific standard deviation is estimated by regressing the absolute residuals on age. The method assumes that the data are, or can be transformed to be, normal at each age, and uses the properties of the half normal distribution. An example is given using 450 measurements of fetal foot l

ISSN:0277-6715    

DOI:10.1002/sim.4780121003

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

年代:1993

数据来源: WILEY

摘要:

AbstractRepeated measures of diet are analysed in an attempt to discover the measurement error properties of various dietary assessment methods. It is customary in such studies to assume that one reference measurement is ‘valid’ (without error) but this assumption is not tenable. An alternative approach, widely used in social science, is to model the covariance matrix of the repeated measures. We apply this methodology to assessments of nitrogen intake, which is essentially equivalent to protein int

ISSN:0277-6715    

DOI:10.1002/sim.4780121004

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn Part I we presented a covariance structure model for analysing measurement error in the assessment of nitrogen intake. In this paper we include data on urine nitrogen excretion which allows a critical assessment of the model proposed. Inclusion of urine nitrogen data produces more pessimistic estimates of the quality of dietary intake measurements and shows that previous assumptions about independence of measurement error were wrong. This underscores the need for well founded assumptions in the analysis of measurement error.

ISSN:0277-6715    

DOI:10.1002/sim.4780121005

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

年代:1993

数据来源: WILEY

摘要:

AbstractA method is outlined for modelling the relationship between breast‐milk production and time from delivery, suitable for data collected longitudinally. The relationship is described using inverse polynomials. In a two‐level model the coefficients are specified as random variables across subjects, allowing within‐ and between‐subject variation to be separately estimated. In a three‐level model, day‐to‐day variation can also be separately estimated. The model is illustrated using data from the Chiang Mai Lactation Project. It allows the use of covariates that vary over time, and provides a method of analysis that is compatible with the practical constraints on the timing of data collection that are inherent in longitu

ISSN:0277-6715    

DOI:10.1002/sim.4780121006

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

年代:1993

数据来源: WILEY

摘要:

AbstractIn clinical trials to compare contraceptives, women are usually asked to record whether or not each day is a bleeding day over the duration of the trial. In this paper we describe how parametric models, which include terms corresponding to covariates recorded for each woman, can be used to analyse data on the occurrence of certain adverse events identified from the diary record. Linear logistic models are used to analyse the probability of prolonged bleeding or amenorrhoea, and log‐linear models are used to analyse the lengths of bleeding episodes. In both cases variation between women is allowed for by including a random effect in the model. The application of our methods is illustrated using a data base made available by the World Health Organizatio

ISSN:0277-6715    

DOI:10.1002/sim.4780121007

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe screening of people for potential coronary heart disease and the monitoring of subjects considered at risk have been performed for some time by measuring total serum cholesterol and its constituent lipoproteins. However, these measurements vary substantially within subjects, making such assessments imprecise. It has been suggested that greater consistency can be achieved by analysing the joint distribution of the individual lipoproteins or of transformed variables derived from them. In this paper we present the results of a laboratory experiment to investigate these ideas with a view to improving current methods of monitoring patients at risk. Nested, random‐effects, multivariate analysis of variance and the log‐ratio analysis of compositions are used to include information on all three lipoproteins simultaneously, and ratios of generalized variances are used to assess and compare the different response variables. The multivariate approach is seen to be far superior to the usual methods. Recommendations are made for routine monitoring and the practical implications are discus

ISSN:0277-6715    

DOI:10.1002/sim.4780121008

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

年代:1993

数据来源: WILEY

摘要:

AbstractWe develop a method for incorporating covariates as regressors in a quality adjusted survival analysis (Q‐TWiST) using Cox's proportional hazards model. The standard Q‐TWiST method assumes that patients progress through a series of health states which differ in quality of life. The Kaplan—Meier product limit method is used to estimate the mean duration of each state by estimating the survival curves for the health state transition times. These estimates provide the basis for quality adjusted survival analysis. In this paper, the survival curves are modelled using Cox's proportional hazards regression. Quality adjusted survival is estimated given sets of covariate values, allowing one to profile patients. The results are useful for investigating how prognostic factors affect treatment benefits in terms of quality of life. We give a brief review of the standard Q‐TWiST method and illustrate the extended methodology with an example from the International Breast Cancer Study Group Trial V comparing short duration versus long duration chemotherapy in the treatment of node‐positive brea

ISSN:0277-6715    

DOI:10.1002/sim.4780121009

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.4780121010

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.4780121011

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

年代:1993

数据来源: WILEY