ISSN:0277-6715    

DOI:10.1002/sim.4780100302

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

年代:1991

数据来源: WILEY

摘要:

AbstractOnly with knowledge of the (prior) distribution of dose‐response parameters in a population, can one determine both the initial dose of a drug for chronic administration to an individual (such as the dose producing a fixed degree of response in a fixed proportion of the population) and an appropriate subsequent (adjusted) dose (such as the dose yielding a desirable response according to the posterior parameter distribution, given an observed response to an initial dose).The currently FDA‐sanctioned design for a dose‐ranging study, the parallel‐dose design, assigns just one of several doses to each patient. It does not provide good information on the distribution of individual dose‐response parameters. A cross‐over design assigns several dose levels to each patient. It therefore can provide better information, but does not resemble clinical practice. Consequently, study participants must be restricted to patients who can tolerate such non‐therapeutic drug exposure, posing problems in extrapolation of study results to other types of patients. A titration or dose‐escalation design begins all patients on placebo and, except for those patients assigned to a placebo‐only group, escalates the dose for a patient at preset intervals only when clinical response at lower doses is inadequate. It both exposes patients to several dose levels and resembles good clinical practice, allowing study of a representative patient sample.We report here the simulation results of parameter estimation for the three designs when the data arise from complex and realistic dose‐response models and/or with certain complications in study execution. The dose‐escalation design clearly performs better overall than the parallel‐dose design for the models considered here, and generally, just a little worse than the cross‐over design. These results support the conclusion that for dose ranging, depending on the demands of the clinical situation, one should use either the cross‐over or

ISSN:0277-6715    

DOI:10.1002/sim.4780100303

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe propose a method to incorporate all types of dropouts in the evaluation of an intervention based on binary data from a titration study. The proposed procedure does not require that the dropouts occur randomly, but instead examines each outcome individually. Our procedure has a built‐in penalty factor in the estimation process that determines the amount of penalty on efficacy parameters due to efficacy‐related dropouts. We also propose a method to estimate the variances associated with the estimates. The results have use in exploration of a potential dose‐response relationship or to answer questions pertinent for phase III studies. We use data from a phase III antihypertension study to illustrate the proc

ISSN:0277-6715    

DOI:10.1002/sim.4780100304

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

年代:1991

数据来源: WILEY

摘要:

AbstractSeveral hormones are released into the blood in a pulsating manner, that is, in short bursts which cause a rapid increase in the circulating concentration. The concentration then declines due to excretion, chemical breakdown, and redistribution into other compartments. Based on a series of observations of the level of hormone in the blood, investigators desire to quantify characteristics of these pulses, that is, timing, amplitude and rate of decay. We describe a statistical model for hormone pulse data and introduce a new method for estimating the characteristics of the pulses.

ISSN:0277-6715    

DOI:10.1002/sim.4780100305

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

年代:1991

数据来源: WILEY

摘要:

AbstractI describe a method for estimating and testing a threshold value in epidemiological studies. A threshold effect indicates an association between a risk factor and a defined outcome above the threshold value but none below it. An important field of application is occupational medicine where, for a lot of chemical compounds and other agents which are non‐arcinogenic health hazards, so‐alled threshold limit values or TLVs are specified. The method is presented within the framework of the logistic regression model, which is widely used in the analysis of the relationship between some explanatory variables and a dependent dichotomous outcome. In most available programs for this and also for other models the concept of a threshold is disregarded. The method for assessing a threshold consists of an estimation procedure using the maximum‐likelihood technique and a test procedure based on the likelihood‐ratio statisticR, following under the null hypothesis (no threshold) a quasi one‐sidedX2distribution with one degree of freedom. This use of this distribution is supported by a simulation study. The method is applied to data from an epidemiological study of the relationship between occupational dust exposure and chronic bronchitic reactions. The results are confirmed by bootstrap r

ISSN:0277-6715    

DOI:10.1002/sim.4780100306

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe point out the connection between electronic monitoring and repeated screening tests, and suggest a flexible and practical method to determine the efficacy of monitoring devices and new technologies. We point out the benefits of the Mantel‐Haenszel estimator of an odds ratio for determining diagnostic test indices. From estimates of sensitivities and specificities, we produce receiver operating characteristic (ROC) curves to compare the performance of two or more monitoring devices in a clinical settin

ISSN:0277-6715    

DOI:10.1002/sim.4780100307

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

年代:1991

数据来源: WILEY

摘要:

AbstractThis paper considers the effect of non‐differential outcome misclassification on the population attributable fraction and the population prevented fraction. I examine the bias in the attributable and the prevented fraction derived from a risk ratio estimate as a function of the sensitivity and specificity of the outcome classification, the true risk ratio, the prevalence of the exposure, and the baseline disease frequency. With outcome misclassified, disease frequency is an important determinant of the magnitude of the bias; the rarer the disease, the more severe is the bias. For both the attributable and the prevented fraction, the specificity of the outcome classification has a greater influence on the magnitude of the bias than the sensitivity; this is in contrast to the dominant effect of sensitivity in situations of exposure misclassification. Also, unlike the findings in the exposure misclassification, the bias due to outcome misclassification does not increase monotonically with increased prevalence of exposure. For the attributable and prevented fraction derived from an odds ratio estimate, the specificity of the outcome classification does not have a greater influence on bias than the sensitivity, and a perfect specificity alone does not lead to unbiased effect estimates if the sensitivity of the outcome classification is imperfec

ISSN:0277-6715    

DOI:10.1002/sim.4780100308

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

年代:1991

数据来源: WILEY

摘要:

AbstractA method is proposed for transforming a class of models having an outcome variable with more than two levels into an equivalent binary model. The polychotomous logistic model is used to demonstrate the method. The equivalency to a simple logistic regression model after some data transformation (augmentation) is shown. The method is applied to the data from two case‐ontrol studies each with two control groups, and further applications are indicate

ISSN:0277-6715    

DOI:10.1002/sim.4780100309

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

年代:1991

数据来源: WILEY

摘要:

AbstractThere is recent interest in classification procedures intended for use only when the response is ordinal. Ordinal response, however, is evident in the parameters estimated by either multinomial logistic or normal discriminant analyses, both of which classify either ordinal or non‐ordinal responses. Further, there may be harm in applying ordinal models inappropriately and ample opportunity to assume mistakenly ordinality in real data sets. Therefore, it becomes important to ascertain whether there is benefit obtained in the appropriate application of ordinal models. This paper presents the results of a simulation study designed to compare classification accuracy of various models. We show that ordinal models classify less accurately than the multinomial logistic and normal discriminant procedures under a variety of circumstances. Until further studies become available, we presently conclude that ordinal models confer no advantage when the main purpose of the analysis is classificatio

ISSN:0277-6715    

DOI:10.1002/sim.4780100310

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

年代:1991

数据来源: WILEY

摘要:

AbstractPrevious studies on the effect of marital bereavement on mortality have suggested various time periods during which the risk of mortality is increased. As many of the studies compared the widowed group with national mortality statistics for the married, there has been no opportunity to adjust for confounders which might themselves be responsible for this increased risk after bereavement. In this paper the various hypotheses proposed are reviewed and then modelled on a dataset of 344 elderly persons who were living with a spouse and who were part of a survey of a population of people aged 75 years and over. The 344 index‐ases and their spouses were followed up for seven years and the times of death (for those who died) of the index‐ase and spouse were noted. The data were analysed by fitting a proportional hazards model to the subject's survival time after adjustment for other factors such as mental and physical health which had already been shown to be associated with mortality. The bereavement effects were fitted as time‐dependent covariates. The best fitting model for females and males indicated an increased relative risk of mortality which lasted for approximately six months after bereavement. In the case of widows this relative risk was significantly increased, being 3.8 with 95 per cent confidence interval (1.4, 10.3) while for widowers the risk was 0.03 with 95 per cent confidence interval (0.00,

ISSN:0277-6715    

DOI:10.1002/sim.4780100311

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

年代:1991

数据来源: WILEY