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1.
In observational studies for the interaction between exposures on a dichotomous outcome of a certain population, usually one parameter of a regression model is used to describe the interaction, leading to one measure of the interaction. In this article we use the conditional risk of an outcome given exposures and covariates to describe the interaction and obtain five different measures of the interaction, that is, difference between the marginal risk differences, ratio of the marginal risk ratios, ratio of the marginal odds ratios, ratio of the conditional risk ratios, and ratio of the conditional odds ratios. These measures reflect different aspects of the interaction. By using only one regression model for the conditional risk, we obtain the maximum-likelihood (ML)-based point and interval estimates of these measures, which are most efficient due to the nature of ML. We use the ML estimates of the model parameters to obtain the ML estimates of these measures. We use the approximate normal distribution of the ML estimates of the model parameters to obtain approximate non-normal distributions of the ML estimates of these measures and then confidence intervals of these measures. The method can be easily implemented and is presented via a medical example.  相似文献   

2.
Analyses of randomised trials are often based on regression models which adjust for baseline covariates, in addition to randomised group. Based on such models, one can obtain estimates of the marginal mean outcome for the population under assignment to each treatment, by averaging the model‐based predictions across the empirical distribution of the baseline covariates in the trial. We identify under what conditions such estimates are consistent, and in particular show that for canonical generalised linear models, the resulting estimates are always consistent. We show that a recently proposed variance estimator underestimates the variance of the estimator around the true marginal population mean when the baseline covariates are not fixed in repeated sampling and provide a simple adjustment to remedy this. We also describe an alternative semiparametric estimator, which is consistent even when the outcome regression model used is misspecified. The different estimators are compared through simulations and application to a recently conducted trial in asthma.  相似文献   

3.
We use logistic model to get point and interval estimates of the marginal risk difference in observational studies and randomized trials with dichotomous outcome. We prove that the maximum likelihood estimate of the marginal risk difference is unbiased for finite sample and highly robust to the effects of dispersing covariates. We use approximate normal distribution of the maximum likelihood estimates of the logistic model parameters to get approximate distribution of the maximum likelihood estimate of the marginal risk difference and then the interval estimate of the marginal risk difference. We illustrate application of the method by a real medical example.  相似文献   

4.
Summary.  In a large, prospective longitudinal study designed to monitor cardiac abnormalities in children born to women who are infected with the human immunodeficiency virus, instead of a single outcome variable, there are multiple binary outcomes (e.g. abnormal heart rate, abnormal blood pressure and abnormal heart wall thickness) considered as joint measures of heart function over time. In the presence of missing responses at some time points, longitudinal marginal models for these multiple outcomes can be estimated by using generalized estimating equations (GEEs), and consistent estimates can be obtained under the assumption of a missingness completely at random mechanism. When the missing data mechanism is missingness at random, i.e. the probability of missing a particular outcome at a time point depends on observed values of that outcome and the remaining outcomes at other time points, we propose joint estimation of the marginal models by using a single modified GEE based on an EM-type algorithm. The method proposed is motivated by the longitudinal study of cardiac abnormalities in children who were born to women infected with the human immunodeficiency virus, and analyses of these data are presented to illustrate the application of the method. Further, in an asymptotic study of bias, we show that, under a missingness at random mechanism in which missingness depends on all observed outcome variables, our joint estimation via the modified GEE produces almost unbiased estimates, provided that the correlation model has been correctly specified, whereas estimates from standard GEEs can lead to substantial bias.  相似文献   

5.
Preference decisions will usually depend on the characteristics of both the judges and the objects being judged. In the analysis of paired comparison data concerning European universities and students' characteristics, it is demonstrated how to incorporate subject-specific information into Bradley–Terry-type models. Using this information it is shown that preferences for universities and therefore university rankings are dramatically different for different groups of students. A log-linear representation of a generalized Bradley–Terry model is specified which allows simultaneous modelling of subject- and object-specific covariates and interactions between them. A further advantage of this approach is that standard software for fitting log-linear models, such as GLIM, can be used.  相似文献   

6.
Chronic disease processes often feature transient recurrent adverse clinical events. Treatment comparisons in clinical trials of such disorders must be based on valid and efficient methods of analysis. We discuss robust strategies for testing treatment effects with recurrent events using methods based on marginal rate functions, partially conditional rate functions, and methods based on marginal failure time models. While all three approaches lead to valid tests of the null hypothesis when robust variance estimates are used, they differ in power. Moreover, some approaches lead to estimators of treatment effect which are more easily interpreted than others. To investigate this, we derive the limiting value of estimators of treatment effect from marginal failure time models and illustrate their dependence on features of the underlying point process, as well as the censoring mechanism. Through simulation, we show that methods based on marginal failure time distributions are shown to be sensitive to treatment effects delaying the occurrence of the very first recurrences. Methods based on marginal or partially conditional rate functions perform well in situations where treatment effects persist or in settings where the aim is to summarizee long-term data on efficacy.  相似文献   

7.
In a randomized controlled trial (RCT), it is possible to improve precision and power and reduce sample size by appropriately adjusting for baseline covariates. There are multiple statistical methods to adjust for prognostic baseline covariates, such as an ANCOVA method. In this paper, we propose a clustering-based stratification method for adjusting for the prognostic baseline covariates. Clusters (strata) are formed only based on prognostic baseline covariates, not outcome data nor treatment assignment. Therefore, the clustering procedure can be completed prior to the availability of outcome data. The treatment effect is estimated in each cluster, and the overall treatment effect is derived by combining all cluster-specific treatment effect estimates. The proposed implementation of the procedure is described. Simulations studies and an example are presented.  相似文献   

8.
An important problem in epidemiology and medical research is the estimation of the causal effect of a treatment action at a single point in time on the mean of an outcome, possibly within strata of the target population defined by a subset of the baseline covariates. Current approaches to this problem are based on marginal structural models, i.e. parametric models for the marginal distribution of counterfactual outcomes as a function of treatment and effect modifiers. The various estimators developed in this context furthermore each depend on a high-dimensional nuisance parameter whose estimation currently also relies on parametric models. Since misspecification of any of these models can lead to severely biased estimates of causal effects, the dependence of current methods on such parametric models represents a major limitation.  相似文献   

9.
We propose a class of additive transformation risk models for clustered failure time data. Our models are motivated by the usual additive risk model for independent failure times incorporating a frailty with mean one and constant variability which is a natural generalization of the additive risk model from univariate failure time to multivariate failure time. An estimating equation approach based on the marginal hazards function is proposed. Under the assumption that cluster sizes are completely random, we show the resulting estimators of the regression coefficients are consistent and asymptotically normal. We also provide goodness-of-fit test statistics for choosing the transformation. Simulation studies and real data analysis are conducted to examine the finite-sample performance of our estimators.  相似文献   

10.
Summary In the log-linear model for bivariate probability functions the conditional and joint probabilities have a simple form. This property make the log-linear parametrization useful when modeling these probabilities is the focus of the investigation. On the contrary, in the log-linear representation of bivariate probability functions, the marginal probabilities have a complex form. So the log-linear models are not useful when the marginal probabilities are of particular interest. In this paper the previous statements are discussed and a model obtained from the log-linear one by imposing suitable constraints on the marginal probabilities is introduced. This work was supported by a M.U.R.S.T. grant.  相似文献   

11.
Ratio estimators of effect are ordinarily obtained by exponentiating maximum-likelihood estimators (MLEs) of log-linear or logistic regression coefficients. These estimators can display marked positive finite-sample bias, however. We propose a simple correction that removes a substantial portion of the bias due to exponentiation. By combining this correction with bias correction on the log scale, we demonstrate that one achieves complete removal of second-order bias in odds ratio estimators in important special cases. We show how this approach extends to address bias in odds or risk ratio estimators in many common regression settings. We also propose a class of estimators that provide reduced mean bias and squared error, while allowing the investigator to control the risk of underestimating the true ratio parameter. We present simulation studies in which the proposed estimators are shown to exhibit considerable reduction in bias, variance, and mean squared error compared to MLEs. Bootstrapping provides further improvement, including narrower confidence intervals without sacrificing coverage.  相似文献   

12.
Summary.  A frequent problem in longitudinal studies is that subjects may miss scheduled visits or be assessed at self-selected points in time. As a result, observed outcome data may be highly unbalanced and the availability of the data may be directly related to the outcome measure and/or some auxiliary factors that are associated with the outcome. If the follow-up visit and outcome processes are correlated, then marginal regression analyses will produce biased estimates. Building on the work of Robins, Rotnitzky and Zhao, we propose a class of inverse intensity-of-visit process-weighted estimators in marginal regression models for longitudinal responses that may be observed in continuous time. This allows us to handle arbitrary patterns of missing data as embedded in a subject's visit process. We derive the large sample distribution for our inverse visit-intensity-weighted estimators and investigate their finite sample behaviour by simulation. Our approach is illustrated with a data set from a health services research study in which homeless people with mental illness were randomized to three different treatments and measures of homelessness (as percentage days homeless in the past 3 months) and other auxiliary factors were recorded at follow-up times that are not fixed by design.  相似文献   

13.
We investigate mixed models for repeated measures data from cross-over studies in general, but in particular for data from thorough QT studies. We extend both the conventional random effects model and the saturated covariance model for univariate cross-over data to repeated measures cross-over (RMC) data; the resulting models we call the RMC model and Saturated model, respectively. Furthermore, we consider a random effects model for repeated measures cross-over data previously proposed in the literature. We assess the standard errors of point estimates and the coverage properties of confidence intervals for treatment contrasts under the various models. Our findings suggest: (i) Point estimates of treatment contrasts from all models considered are similar; (ii) Confidence intervals for treatment contrasts under the random effects model previously proposed in the literature do not have adequate coverage properties; the model therefore cannot be recommended for analysis of marginal QT prolongation; (iii) The RMC model and the Saturated model have similar precision and coverage properties; both models are suitable for assessment of marginal QT prolongation; and (iv) The Akaike Information Criterion (AIC) is not a reliable criterion for selecting a covariance model for RMC data in the following sense: the model with the smallest AIC is not necessarily associated with the highest precision for the treatment contrasts, even if the model with the smallest AIC value is also the most parsimonious model.  相似文献   

14.
Calibration in macroeconomics involves choosing fre parameters by matching certain moments of simulted models with those of data. We formally examine this method by treating the process of calibration as an econometric estimator. A numerical version of the Mehra-Prescott (1985) economy is the setting for an evaluation of calibration estimators via Monte Carlo methods. While these estimators sometimes have reasonable finite-sample properties they are not robust to mistakes in setting non-free parameters. In contrast, generalized method-of-moments (GMM) estimators have satisfactory finite-sample characteristics, quick convergence, and informational requirements less stringent than those of calibration estimators. In dynamic equilibrium models in which GMM is infeasible we offer some suggestions for improving estimates based on calibration methodology.  相似文献   

15.
We explore the impact of time-varying subsequent therapy on the statistical power and treatment effects in survival analysis. The marginal structural model (MSM) with stabilized inverse probability treatment weights (sIPTW) was used to account for the effects due to the subsequent therapy. Simulations were performed to compare the MSM-sIPTW method with the conventional method without accounting for the time-varying covariate such as subsequent therapy that is dependent on the initial response of the treatment effect. The results of the simulations indicated that the statistical power, thereby the Type I error, of the trials to detect the frontline treatment effect could be inflated if no appropriate adjustment was made for the impact due to the add-on effects of the subsequent therapy. Correspondingly, the hazard ratio between the treatment groups may be overestimated by the conventional analysis methods. In contrast, MSM-sIPTW can maintain the Type I error rate and gave unbiased estimates of the hazard ratio for the treatment. Two real examples were used to discuss the potential clinical implications. The study demonstrated the importance of accounting for time-varying subsequent therapy for obtaining unbiased interpretation of data.  相似文献   

16.
A common problem for longitudinal data analyses is that subjects follow-up is irregular, often related to the past outcome or other factors associated with the outcome measure that are not included in the regression model. Analyses unadjusted for outcome-dependent follow-up yield biased estimates. We propose a longitudinal data analysis that can provide consistent estimates in regression models that are subject to outcome-dependent follow-up. We focus on semiparametric marginal log-link regression with arbitrary unspecified baseline function. Based on estimating equations, the proposed class of estimators are root n consistent and asymptotically normal. We present simulation studies that assess the performance of the estimators under finite samples. We illustrate our approach using data from a health services research study.  相似文献   

17.
In many biomedical studies with recurrent events, some markers can only be measured when events happen. For example, medical cost attributed to hospitalization can only incur when patients are hospitalized. Such marker data are contingent on recurrent events. In this paper, we present a proportional means model for modelling the markers using the observed covariates contingent on the recurrent event. We also model the recurrent event via a marginal rate model. Estimating equations are constructed to derive the point estimators for the parameters in the proposed models. The estimators are shown to be asymptotically normal. Simulation studies are conducted to examine the finite-sample properties of the proposed estimators and the proposed method is applied to a data set from the Vitamin A Community Trial.  相似文献   

18.
Calibration in macroeconomics involves choosing fre parameters by matching certain moments of simulted models with those of data. We formally examine this method by treating the process of calibration as an econometric estimator. A numerical version of the Mehra-Prescott (1985) economy is the setting for an evaluation of calibration estimators via Monte Carlo methods. While these estimators sometimes have reasonable finite-sample properties they are not robust to mistakes in setting non-free parameters. In contrast, generalized method-of-moments (GMM) estimators have satisfactory finite-sample characteristics, quick convergence, and informational requirements less stringent than those of calibration estimators. In dynamic equilibrium models in which GMM is infeasible we offer some suggestions for improving estimates based on calibration methodology.  相似文献   

19.
We consider causal inference in randomized studies for survival data with a cure fraction and all-or-none treatment non compliance. To describe the causal effects, we consider the complier average causal effect (CACE) and the complier effect on survival probability beyond time t (CESP), where CACE and CESP are defined as the difference of cure rate and non cured subjects’ survival probability between treatment and control groups within the complier class. These estimands depend on the distributions of survival times in treatment and control groups. Given covariates and latent compliance type, we model these distributions with transformation promotion time cure model whose parameters are estimated by maximum likelihood. Both the infinite dimensional parameter in the model and the mixture structure of the problem create some computational difficulties which are overcome by an expectation-maximization (EM) algorithm. We show the estimators are consistent and asymptotically normal. Some simulation studies are conducted to assess the finite-sample performance of the proposed approach. We also illustrate our method by analyzing a real data from the Healthy Insurance Plan of Greater New York.  相似文献   

20.
In longitudinal studies, observation times are often irregular and subject‐specific. Frequently they are related to the outcome measure or other variables that are associated with the outcome measure but undesirable to condition upon in the model for outcome. Regression analyses that are unadjusted for outcome‐dependent follow‐up then yield biased estimates. The authors propose a class of inverse‐intensity rate‐ratio weighted estimators in generalized linear models that adjust for outcome‐dependent follow‐up. The estimators, based on estimating equations, are very simple and easily computed; they can be used under mixtures of continuous and discrete observation times. The predictors of observation times can be past observed outcomes, cumulative values of outcome‐model covariates and other factors associated with the outcome. The authors validate their approach through simulations and they illustrate it using data from a supported housing program from the US federal government.  相似文献   

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