ISSN:0277-6715    

DOI:10.1002/sim.4780111602

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

年代:1992

数据来源: WILEY

摘要:

AbstractThis paper considers the statistical complexities that arise due to outcome related drop‐outs in longitudinal clinical trials of the randomized parallel groups design with fixed assessment times and an explanatory aim. The shortcomings of currently popular methods of coping with the problem of drop‐outs are discussed. It is proposed that progress can be made by applying the modern methodology that was primarily developed for sample surveys with non‐response and for observational studies. A practical application using the Hamilton Rating Scale for Depression is pres

ISSN:0277-6715    

DOI:10.1002/sim.4780111603

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

年代:1992

数据来源: WILEY

摘要:

AbstractEthical considerations in a cancer phase I trial require a design allowing determination of the maximum tolerated dose with a minimum number of patients treated at low ineffectual or high overly toxic doses. It would also be advantageous to complete the phase I trial in as short a period of time and with as few patients as possible to allow further resources for later studies in which patients are treated at the optimal dose. Several dose escalation schemes are compared. These are the Fibonacci, two two‐stage schemes, and a proposed scheme which uses knowledge of all toxicity grades. Estimates of the maximum tolerated dose are obtained and compared using the dose escalation schemes alone, a logit model, and a proposed mean response model. Confidence intervals using the delta method are obtained from the logit and mean response models. The proposed scheme and the two‐stage schemes have the advantage of requiring fewer patients, particularly at low doses. Confidence intervals obtained from the mean response model have better coverage than those from the logit model. Data from a cancer phase I trial of dipyridamole and acivicin is presented to illustrate the meth

ISSN:0277-6715    

DOI:10.1002/sim.4780111604

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

年代:1992

数据来源: WILEY

摘要:

AbstractThis paper contains a proposition related to the publication of meta‐analyses of clinical trials. We consider the situation where the results of a number of trials are summarized by a common or typical odds ratio. We show that stating such an odds ratio as the summary of evidence from a number of trials can be misleading if certain systematic differences between trials exist. In such cases the author should state not just one odds ratio but also its dependence on the relevant characteristics of the trials. In particular, we propose that those reporting a meta‐analysis state in advance a (limited) number of variables to be considered for potential interaction with the exposure (risk factor or treatment) of interest. The list might include centre size and the odds in the placebo or control group if such an effect isa prioriclinically plausible. The trials should be ordered according to each of these variables and a trend test for the odds ratio should be computed. Apart from a ‘genuine’ effect, an appreciable interaction could also be indicative of the (multiplicative) odds ratio being an inappropriate measure for the particular meta‐analysis. Without any consideration as to the possibility of interaction, the meta‐analysis should be considered incomplete. If such an interaction exists, the odds ratio should be stated as a function of the interacting variable, either as a formula or (preferably) in a table stating the odds ratio for a number of different values of the interacting variable, and not as a single summar

ISSN:0277-6715    

DOI:10.1002/sim.4780111605

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe estimation of attributable risk in the presence of confounding and effect modification is studied in this paper. Different adjustment methods for the attributable risk are reviewed. The results of a simulation study comparing these methods under the unrestricted multinomial sampling model are reported. From the study it is concluded that the maximum likelihood estimator resulting from the ‘case load weighting’ of the stratum‐specific attributable risk estimates will be the best overall choice in all practical situations with relatively large sample sizes. Other adjusted attributable risk estimators depend heavily on the underlying structure of the multinomial

ISSN:0277-6715    

DOI:10.1002/sim.4780111606

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

年代:1992

数据来源: WILEY

摘要:

AbstractA common problem in the statistical analysis of clinical studies is the selection of those variables in the framework of a regression model which might influence the outcome variable. Stepwise methods have been available for a long time, but as with many other possible strategies, there is a lot of criticism of their use. Investigations of the stability of a selected model are often called for, but usually are not carried out in a systematic way. Since analytical approaches are extremely difficult, data‐dependent methods might be an useful alternative. Based on a bootstrap resampling procedure, Chen and George investigated the stability of a stepwise selection procedure in the framework of the Cox proportional hazard regression model. We extend their proposal and develop a bootstrap‐model selection procedure, combining the bootstrap method with existing selection techniques such as stepwise methods. We illustrate the proposed strategy in the process of model building by using data from two cancer clinical trials featuring two different situations commonly arising in clinical research. In a brain tumour study the adjustment for covariates in an overall treatment comparison is of primary interest calling for the selection of even ‘mild’ effects. In a prostate cancer study we concentrate on the analysis of treatment‐covariate interactions demanding that only ‘strong’ effects should be selected. Both variants of the strategy will be demonstrated analysing the clinical trials with a Cox model, but they can be applied in other types of regression with obvious and straightforward

ISSN:0277-6715    

DOI:10.1002/sim.4780111607

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

年代:1992

数据来源: WILEY

摘要:

AbstractStandard models for the analysis of repeated measurements assume a common response profile for all experimental units within a treatment group. However, in many applications this under‐represents the nature of the response. There may be several distinct modes of response within a group (for example, responders versus non‐responders to a given treatment), or there may be a set of distinct response profiles which are common to all the treatment groups. In these situations the effect of treatment can be characterized both by the shape of the fitted profiles and by estimating the proportion of cases who exhibit each particular response profile. This paper describes how such experiments may be analysed through the introduction of a latent variable into the standard model. Maximum likelihood estimation is straight‐forward using the EM algorithm. Model choice requires some care, but good‐fitting models can be identified via inspection of residuals and the use of empirical semi‐variogram plots. Once the number of distinct profiles has been determined, treatment effects can be investigated using likelihood‐ratio statistics. The approach is illustrated with a re‐analysis of a dataset first described by Griz

ISSN:0277-6715    

DOI:10.1002/sim.4780111608

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe results of 839 platelet transfusions in 115 patients were studied to establish the relative importance of 10 clinical factors in determining the efficacy of pooled donor transfusions. Efficacy was measured by the one hour corrected increment in platelet count. The number of transfusions available for study from individual patients varied widely from 1 to 37. Two methods of analysis are presented. The first makes assumptions about the correlation between transfusions within patients, and the variation between patients. The second is based on a repeated sampling procedure whereby unbiased estimates of the parameters of interest are obtained from random samples containing only one transfusion per patient.

ISSN:0277-6715    

DOI:10.1002/sim.4780111609

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe identification of discrete hormonal secretory pulses is of critical importance in clinical endocrinology. Pulses are defined as sudden increases in hormone concentration followed by exponential decay. We propose a model‐based iterative procedure for pulse detection in pulsatile hormone time series. Our model is seen to be analogous to the model for innovation outliers in autoregressive series, and outlier detection techniques for pulse identification are adapted to the endocrine context. An original feature of the procedure is that it distinguishes between true pulses and gross observation outliers in the series. Simulation experiments are used to investigate the behaviour of the method under physiologically or clinically relevant circumstances. Five experimental endocrine series from rhesus monkeys, where the times of the pulses are known from the concomitant recording of the electrical activity of the hypothalamus, are analyse

ISSN:0277-6715    

DOI:10.1002/sim.4780111610

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

年代:1992

数据来源: WILEY

摘要:

AbstractNon‐invasive ambulatory blood pressure monitoring is an appropriate technique for the identification of the target population requiring antihypertensive treatment, since the systematic bias seen in casual clinic measurement is removed. The use of the technique in controlled clinical trials leads to a reduction in the sample size required to show a treatment difference in antihypertensive effect compared to sporadic single measurements, although in practice the number of recruited patients can considerably exceed the number of evaluable patients, due to poor compliance or incompleteness of data. In addition, the equality of observation essential in clinical trials cannot be controlled to the same degree as is possible with clinic measurements. Comparison of estimators of the overall characteristic blood pressure reveals that the 24‐hour mean value produces an adequate estimator. A description of the individual blood pressure profile is obtained using smoothing procedures, the moving interval average providing a robust and simple approach. Clinically meaningful characteristics of the profile are difficult to define due to a dearth of information on prognostic importance of the features of the 24‐hour blood pressure profile. Smoothed individual profiles can be combined to produce graphical descriptive treatment group summ

ISSN:0277-6715    

DOI:10.1002/sim.4780111611

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

年代:1992

数据来源: WILEY