The mixture of a distribution of responses from untreated patients and a shift of that distribution is a useful model for the responses from a group of treated patients. The mixture model accounts for the fact that not all the patients in the treated group will respond to the treatment and consequently their responses follow the same distribution as the responses from untreated patients. The treatment effect in this context consists of both the fraction of the treated patients that are responders and the magnitude of the shift in the distribution for the responders. In this article, we introduce inference based on a pseudo-likelihood approach and compare it with an existing method of moment approach. An extensive simulation study is used to compare robust performance of the two approaches regarding point estimation, confidence regions, and confidence intervals. The methods are demonstrated on an illustrative blood pressure data set.

Multivariate panel count data arise when there are multiple types of recurrent events, and the observation for each study subject consists of the number of recurrent events of each type between two successive examinations. We formulate the effects of potentially time-dependent covariates on multiple types of recurrent events through proportional rates models, while leaving the dependence structures of the related recurrent events completely unspecified. We employ nonparametric maximum pseudo-likelihood estimation under the working assumptions that all types of events are independent and each type of event is a nonhomogeneous Poisson process, and we develop a simple and stable EM-type algorithm. We show that the resulting estimators of the regression parameters are consistent and asymptotically normal, with a covariance matrix that can be estimated consistently by a sandwich estimator. In addition, we develop a class of graphical and numerical methods for checking the adequacy of the fitted model. Finally, we evaluate the performance of the proposed methods through simulation studies and analysis of a skin cancer clinical trial.

For low prevalence disease, we consider estimation of the odds ratio for two specified groups of individuals using group testing data. Broadly the two groups may be classified as \"the exposed\" and \"the unexposed.\" Often in observational studies, the exposure status is not correctly recorded. In addition, diagnostic tests are rarely completely accurate. The proposed model accounts for imperfect sensitivity and specificity of diagnostic tests along with the misclassification in the exposure status. For model identifiability, we make use of internal validation data, where a subsample of reasonably small size is selected from the original sample by simple random sampling without replacement. Pseudo-maximum likelihood method is employed for the estimation of the model parameters. The performance of group testing methodology is compared with individual testing for different parametric configurations. A limited data study related to COVID-19 prevalence is performed to illustrate the methodology.

This paper presents a class of regression models with cumulative logistic functions that are chiefly designed to analyse spatially dependent ordinal data. In contrast to previous works, the proposed model requires neither the sites to be regularly spaced nor the assumption of an underlying continuous variable. It belongs to a more general class of Markov random field models, and can be considered an extension of the ordinal regression model with the proportional odds link function. Our proposed model allows practitioners to interpret the model parameters using odds ratios. Apart from the theoretical developments, this work also highlights the practical aspects of model fitting, including parameterisation, selection of neighbourhood, and calculation of standard errors. Simulation studies with regularly and irregularly spaced sites were conducted. Modelling strategies including pseudo-likelihood methods were found to be useful in both settings. The proposed model and the non-spatial counterpart were applied to the daily air quality index measured in the United Kingdom. The results indicate the presence of spatial effects and the incorporation of spatial effects led to better model performance in terms of various goodness-of-fit measures.

Bivariate random-effects models represent a recommended approach for meta-analysis of diagnostic test accuracy, jointly modeling study-specific sensitivity and specificity. As the severity of the disease status can vary across studies, a proper analysis should account for the dependence of the accuracy measures on the disease prevalence. To this aim, trivariate generalized linear mixed-effects models have been proposed in the literature, although computational difficulties strongly limit their applicability. In addition, the attention has been mainly paid to cohort studies, where the study-specific disease prevalence can be estimated from, while information from case-control studies is often neglected. To overcome such limits, this article introduces a trivariate approximate normal model, which accounts for disease prevalence along with accuracy measures in cohort studies and sensitivity and specificity in case-control studies. The model represents an extension of the bivariate normal mixed-effects model originally developed for meta-analysis not accounting for disease prevalence, under an approximate normal within-study distribution for the logit of estimated sensitivity and specificity. The components of the approximate within-study covariance matrix are derived and the likelihood function is obtained in closed-form. The approximate likelihood approach is compared to that based on the exact within-study distribution and to its modifications following a pseudo-likelihood strategy aimed at reducing the computational effort. The comparison is based on simulation studies in a variety of scenarios, and illustrated in a meta-analysis about the accuracy of a test to diagnose fungal infection and a meta-analysis of a noninvasive test to detect colorectal cancer.

In this paper, the support of the joint probability distribution of categorical variables in the total population is treated as unknown. From a general total population model with unknown support, a general subpopulation model with its support equal to the set of all observed score patterns is derived. In maximum likelihood estimation of the parameters of any such subpopulation model, the evaluation of the log-likelihood function only requires the summation over a number of terms equal to at most the sample size. It is made clear that the parameters of a hypothesized total population model are consistently and asymptotically efficiently estimated by the values that maximize the log-likelihood function of the corresponding subpopulation model. Next, new likelihood ratio goodness-of-fit tests are proposed as alternatives to the Pearson chi-square goodness-of-fit test and the likelihood ratio test against the saturated model. In a simulation study, the asymptotic bias and efficiency of maximum likelihood estimators and the asymptotic performance of the goodness-of-fit tests are investigated.

Semi-competing risks data often arise in medical studies where the terminal event (e.g., death) censors the non-terminal event (e.g., cancer recurrence), but the non-terminal event does not prevent the subsequent occurrence of the terminal event. This article considers regression modeling of semi-competing risks data to assess the covariate effects on the respective non-terminal and terminal event times. We propose a copula-based framework for semi-competing risks regression with time-varying coefficients, where the dependence between the non-terminal and terminal event times is characterized by a copula and the time-varying covariate effects are imposed on two marginal regression models. We develop a two-stage inferential procedure for estimating the association parameter in the copula model and time-varying regression parameters. We evaluate the finite sample performance of the proposed method through simulation studies and illustrate the method through an application to Surveillance, Epidemiology, and End Results-Medicare data for elderly women diagnosed with early-stage breast cancer and initially treated with breast-conserving surgery.

In this paper, the spatial arrangement and possible interactions between epidermal nerve fibre endings are investigated and modelled by using confocal microscopy data. We are especially interested in possible differences between patterns from healthy volunteers and patients suffering from mild diabetic neuropathy. The locations of the points, where nerves enter the epidermis, the first branching points and the points where the nerve fibres terminate, are regarded as realizations of spatial point processes. We propose an anisotropic point process model for the locations of the nerve fibre endings in three dimensions, where the points interact in cylindrical regions. First, the locations of end points in R 2 $\\mathbb {R}^2$ are modelled as clusters around the branching points and then, the model is extended to three dimensions using a pairwise interaction Markov field model with cylindrical neighbourhood for the z-coordinates conditioned on the planar locations of the points. We fit the model to samples taken from healthy subjects and subjects suffering from diabetic neuropathy. In both groups, after a hardcore radius, there is some attraction between the end points. However, the range and strength of attraction are not the same in the two groups. Performance of the model is evaluated by using a cylindrical version of Ripley\'s K function due to the anisotropic nature of the data. Our findings suggest that the proposed model is able to capture the 3D spatial structure of the end points.

Functional data are often extremely high-dimensional and exhibit strong dependence structures but can often prove valuable for both prediction and inference. The literature on functional data analysis is well developed; however, there has been very little work involving functional data in complex survey settings. Motivated by physical activity monitor data from the National Health and Nutrition Examination Survey (NHANES), we develop a Bayesian model for functional covariates that can properly account for the survey design. Our approach is intended for non-Gaussian data and can be applied in multivariate settings. In addition, we make use of a variety of Bayesian modeling techniques to ensure that the model is fit in a computationally efficient manner. We illustrate the value of our approach through two simulation studies as well as an example of mortality estimation using NHANES data.

In diagnostic radiology, the multireader multicase (MRMC) design and the free-response receiver operating characteristics (FROC) method are often used in combination. The cross-correlated data generated by the MRMC-FROC study leads to difficulties in the corresponding analysis, and the need to include covariates in the model further complicates the subsequent analysis. In this paper, we propose a regression approach based on three new measures with good interpretability. The correlation structure of the original test results is taken directly into account in the estimation procedure. The proposed method also allows the inclusion of continuous or discrete covariates. Consistent and asymptotically normal estimators are derived for the new measures. Simulation studies are conducted to evaluate the performance of the proposed approach. The simulation results show that the regression approach performs well under a wide range of scenarios. We also apply the proposed regression approach to a diagnostic study of computer-aided diagnosis in lung cancer.