Unconditional analogues of Cochran–Mantel–Haenszel tests

The Cochran–Mantel–Haenszel tests are a suite of tests that are usually defined as conditional tests, tests that assume all marginal totals are known before sighting the data. Here unconditional analogues of these tests are defined for the more usual situation when the marginal totals are not known before sighting the data.     

Measurement Error Correction by Exploiting Gene–Environment Independence in Family‐Based Case–Control Studies

Abstract. Family‐based case–control designs are commonly used in epidemiological studies for evaluating the role of genetic susceptibility and environmental exposure to risk factors in the etiology of rare diseases. Within this framework, it is often reasonable to assume genetic susceptibility and environmental exposure being conditionally independent of each other within families in the source population. We focus on this setting to explore the situation of measurement error affecting the assessment of the environmental exposure. We correct for measurement error through a likelihood‐based method. We exploit a conditional likelihood approach to relate the probability of disease to the genetic and the environmental risk factors. We show that this approach provides less biased and more efficient results than that based on logistic regression. Regression calibration, instead, provides severely biased estimators of the parameters. The comparison of the correction methods is performed through simulation, under common measurement error structures.     

On a Unified Generalized Quasi–likelihood Approach for Familial–Longitudinal Non‐Stationary Count Data

Abstract. In this paper, conditional on random family effects, we consider an auto‐regression model for repeated count data and their corresponding time‐dependent covariates, collected from the members of a large number of independent families. The count responses, in such a set up, unconditionally exhibit a non‐stationary familial–longitudinal correlation structure. We then take this two‐way correlation structure into account, and develop a generalized quasilikelihood (GQL) approach for the estimation of the regression effects and the familial correlation index parameter, whereas the longitudinal correlation parameter is estimated by using the well‐known method of moments. The performance of the proposed estimation approach is examined through a simulation study. Some model mis‐specification effects are also studied. The estimation methodology is illustrated by analysing real life healthcare utilization count data collected from 36 families of size four over a period of 4 years.     

Model averaging inconcentration–QT analyses

This article describes how a frequentist model averaging approach can be used for concentration–QT analyses in the context of thorough QTc studies. Based on simulations, we have concluded that starting from three candidate model families (linear, exponential, and Emax) the model averaging approach leads to treatment effect estimates that are quite robust with respect to the control of the type I error in nearly all simulated scenarios; in particular, with the model averaging approach, the type I error appears less sensitive to model misspecification than the widely used linear model. We noticed also few differences in terms of performance between the model averaging approach and the more classical model selection approach, but we believe that, despite both can be recommended in practice, the model averaging approach can be more appealing because of some deficiencies of model selection approach pointed out in the literature. We think that a model averaging or model selection approach should be systematically considered for conducting concentration–QT analyses. Copyright © 2016 John Wiley & Sons, Ltd.     

New perspective on the benefits of the gene–environment independence in case–control studies

We study the benefit of exploiting the gene–environment independence (GEI) assumption for inferring the joint effect of genotype and environmental exposure on disease risk in a case–control study. By transforming the problem into a constrained maximum likelihood estimation problem we derive the asymptotic distribution of the maximum likelihood estimator (MLE) under the GEI assumption (MLE‐GEI) in a closed form. Our approach uncovers a transparent explanation of the efficiency gained by exploiting the GEI assumption in more general settings, thus bridging an important gap in the existing literature. Moreover, we propose an easy‐to‐implement numerical algorithm for estimating the model parameters in practice. Finally, we conduct simulation studies to compare the proposed method with the traditional prospective logistic regression method and the case‐only estimator. The Canadian Journal of Statistics 47: 473–486; 2019 © 2019 Statistical Society of Canada