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We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. [ABSTRACT FROM AUTHOR]

We investigate the effects of measurement error on the estimation of nonparametric variance functions. We show that either ignoring measurement error or direct application of the simulation extrapolation, SIMEX, method leads to inconsistent estimators. Nevertheless, the direct SIMEX method can reduce bias relative to a naive estimator. We further propose a permutation SIMEX method that leads to consistent estimators in theory. The performance of both the SIMEX methods depends on approximations to the exact extrapolants. Simulations show that both the SIMEX methods perform better than ignoring measurement error. The methodology is illustrated using microarray data from colon cancer patients. [ABSTRACT FROM AUTHOR]

For many diseases, it is difficult or impossible to establish a definitive diagnosis because a perfect “gold standard” may not exist or may be too costly to obtain. In this paper, we propose a method to use continuous test results to estimate prevalence of disease in a given population and to estimate the effects of factors that may influence prevalence. Motivated by a study of human herpesvirus 8 among children with sickle-cell anemia in Uganda, where 2 enzyme immunoassays were used to assess infection status, we fit 2-component multivariate mixture models. We model the component densities using parametric densities that include data transformation as well as flexible transformed models. In addition, we model the mixing proportion, the probability of a latent variable corresponding to the true unknown infection status, via a logistic regression to incorporate covariates. This model includes mixtures of multivariate normal densities as a special case and is able to accommodate unusual shapes and skewness in the data. We assess model performance in simulations and present results from applying various parameterizations of the model to the Ugandan study. [ABSTRACT FROM AUTHOR]

Hjort & Claeskens (2003) developed an asymptotic theory for model selection, model averaging and subsequent inference using likelihood methods in parametric models, along with associated confidence statements. In this article, we consider a semiparametric version of this problem, wherein the likelihood depends on parameters and an unknown function, and model selection/averaging is to be applied to the parametric parts of the model. We show that all the results of Hjort & Claeskens hold in the semiparametric context, if the Fisher information matrix for parametric models is replaced by the semiparametric information bound for semiparametric models, and if maximum likelihood estimators for parametric models are replaced by semiparametric efficient profile estimators. Our methods of proof employ Le Cams contiguity lemmas, leading to transparent results. The results also describe the behaviour of semiparametric model estimators when the parametric component is misspecified, and also have implications for pointwise-consistent model selectors. [ABSTRACT FROM AUTHOR]

We consider partially linear models of the form Y = XTβ + ν(Z) + ɛ when the response variable Y is sometimes missing with missingness probability π depending on (X, Z), and the covariate X is measured with error, where ν(z) is an unspecified smooth function. The missingness structure is therefore missing not at random, rather than the usual missing at random. We propose a class of semiparametric estimators for the parameter of interest β, as well as for the population mean E(Y). The resulting estimators are shown to be consistent and asymptotically normal under general assumptions. To construct a confidence region for β, we also propose an empirical-likelihood-based statistic, which is shown to have a chi-squared distribution asymptotically. The proposed methods are applied to an AIDS clinical trial dataset. A simulation study is also reported. [ABSTRACT FROM AUTHOR]

We propose a modelling framework to study the relationship between two paired longitudinally observed variables. The data for each variable are viewed as smooth curves measured at discrete time-points plus random errors. While the curves for each variable are summarized using a few important principal components, the association of the two longitudinal variables is modelled through the association of the principal component scores. We use penalized splines to model the mean curves and the principal component curves, and cast the proposed model into a mixed-effects model framework for model fitting, prediction and inference. The proposed method can be applied in the difficult case in which the measurement times are irregular and sparse and may differ widely across individuals. Use of functional principal components enhances model interpretation and improves statistical and numerical stability of the parameter estimates. [ABSTRACT FROM AUTHOR]

Genetic epidemiologic studies often involve investigation of the association of a disease with a genomic region in terms of the underlying haplotypes, that is the combination of alleles at multiple loci along homologous chromosomes. In this article, we consider the problem of estimating haplotype–environment interactions from case–control studies when some of the environmental exposures themselves may be influenced by genetic susceptibility. We specify the distribution of the diplotypes (haplotype pair) given environmental exposures for the underlying population based on a novel semiparametric model that allows haplotypes to be potentially related with environmental exposures, while allowing the marginal distribution of the diplotypes to maintain certain population genetics constraints such as Hardy–Weinberg equilibrium. The marginal distribution of the environmental exposures is allowed to remain completely nonparametric. We develop a semiparametric estimating equation methodology and related asymptotic theory for estimation of the disease odds ratios associated with the haplotypes, environmental exposures, and their interactions, parameters that characterize haplotype–environment associations and the marginal haplotype frequencies. The problem of phase ambiguity of genotype data is handled using a suitable expectation–maximization algorithm. We study the finite-sample performance of the proposed methodology using simulated data. An application of the methodology is illustrated using a case–control study of colorectal adenoma, designed to investigate how the smoking-related risk of colorectal adenoma can be modified by “NAT2,” a smoking-metabolism gene that may potentially influence susceptibility to smoking itself. [ABSTRACT FROM AUTHOR]