Classical multivariate principal component analysis has been extended to functional data and termed functional principal component analysis (FPCA). Most existing FPCA approaches do not accommodate covariate information, and it is the goal of this paper to develop two methods that do. In the first approach, both the mean and covariance functions depend on the covariate $Z$ and time scale $t$ while in the second approach only the mean function depends on the covariate $Z$. Both new approaches accommodate additional measurement errors and functional data sampled at regular time grids as well as sparse longitudinal data sampled at irregular time grids. The first approach to fully adjust both the mean and covariance functions adapts more to the data but is computationally more intensive than the approach to adjust the covariate effects on the mean function only. We develop general asymptotic theory for both approaches and compare their performance numerically through simulation studies and a data set.
This paper investigates the high-dimensional linear regression with highly correlated covariates. In this setup, the traditional sparsity assumption on the regression coefficients often fails to hold, and consequently many model selection procedures do not work. To address this challenge, we model the variations of covariates by a factor structure. Specifically, strong correlations among covariates are explained by common factors and the remaining variations are interpreted as idiosyncratic components of each covariate. This leads to a factor-adjusted regression model with both common factors …
In contemporary scientific research, it is of great interest to predict a categorical response based on a high-dimensional tensor (i.e. multi-dimensional array) and additional covariates. This mixture of different types of data leads to challenges in statistical analysis. Motivated by applications in science and engineering, we propose a comprehensive and interpretable discriminant analysis model, called CATCH model (in short for Covariate-Adjusted Tensor Classification in High-dimensions), which efficiently integrates the covariates and the tensor to predict the categorical outcome. The CATCH…
This paper studies model selection consistency for high dimensional sparse regression when data exhibits both cross-sectional and serial dependency. Most commonly-used model selection methods fail to consistently recover the true model when the covariates are highly correlated. Motivated by econometric studies, we consider the case where covariate dependence can be reduced through factor model, and propose a consistent strategy named Factor-Adjusted Regularized Model Selection (FarmSelect). By separating the latent factors from idiosyncratic components, we transform the problem from model sele…
Functional Principal Component Analysis (FPCA) has become a widely-used dimension reduction tool for functional data analysis. When additional covariates are available, existing FPCA models integrate them either in the mean function or in both the mean function and the covariance function. However, methods of the first kind are not suitable for data that display second-order variation, while those of the second kind are time-consuming and make it difficult to perform subsequent statistical analyses on the dimension-reduced representations. To tackle these issues, we introduce an eigen-adjusted…
In many longitudinal settings, time-varying covariates may not be measured at the same time as responses and are often prone to measurement error. Naive last-observation-carried-forward methods incur estimation biases, and existing kernel-based methods suffer from slow convergence rates and large variations. To address these challenges, we propose a new functional calibration approach to efficiently learn longitudinal covariate processes based on sparse functional data with measurement error. Our approach, stemming from functional principal component analysis, calibrates the unobserved synchro…
We present a flexible Bayesian semiparametric mixed model for longitudinal data analysis in the presence of potentially high-dimensional categorical covariates. Building on a novel hidden Markov tensor decomposition technique, our proposed method allows the fixed effects components to vary between dependent random partitions of the covariate space at different time points. The mechanism not only allows different sets of covariates to be included in the model at different time points but also allows the selected predictors' influences to vary flexibly over time. Smooth time-varying additive ran…
Structural magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients. The formation of these lesions is a complex process involving inflammation, tissue damage, and tissue repair, all of which are visible on MRI. Here we characterize the lesion formation process on longitudinal, multi-sequence structural MRI from 34 MS patients and relate the longitudinal changes we observe within lesions to therapeutic interventions. In this article, we first outline a pipeline to extract voxel level, multi-sequence longitudinal profiles from four MRI seq…
It is often important to incorporating covariate information in the design of clinical trials. In literature, there are many designs of using stratification and covariate-adaptive randomization to balance on certain known covariate. Recently Zhang, Hu, Cheung and Chan (2007) have proposed a family of covariate-adjusted response-adaptive (CARA) designs and studied their asymptotic properties. However, these CARA designs often have high variabilities. In this paper, we propose a new family of covariate-adjusted response-adaptive (CARA) designs. We show that the new designs have smaller variabili…
We consider covariate adjusted regression (CAR), a regression method for situations where predictors and response are observed after being distorted by a multiplicative factor. The distorting factors are unknown functions of an observable covariate, where one specific distorting function is associated with each predictor or response. The dependence of both response and predictors on the same confounding covariate may alter the underlying regression relation between undistorted but unobserved predictors and response. We consider a class of highly flexible adjustment methods for parameter estima…
In statistical learning, high covariate dimensionality poses challenges for robust prediction and inference. To address this challenge, supervised dimension reduction is often performed, where dependence on the outcome is maximized for a selected covariate subspace with smaller dimensionality. Prevalent dimension reduction techniques assume data are $i.i.d.$, which is not appropriate for longitudinal data comprising multiple subjects with repeated measurements over time. In this paper, we derive a decomposition of the Hilbert-Schmidt Independence Criterion as a supervised loss function for lon…
A tuning-free procedure is proposed to estimate the covariate-adjusted Gaussian graphical model. For each finite subgraph, this estimator is asymptotically normal and efficient. As a consequence, a confidence interval can be obtained for each edge. The procedure enjoys easy implementation and efficient computation through parallel estimation on subgraphs or edges. We further apply the asymptotic normality result to perform support recovery through edge-wise adaptive thresholding. This support recovery procedure is called ANTAC, standing for Asymptotically Normal estimation with Thresholding af…
We propose a novel approach to estimate the Cox model with temporal covariates. Our new approach treats the temporal covariates as arising from a longitudinal process which is modeled jointly with the event time. Different from the literature, the longitudinal process in our model is specified as a bounded variational process and determined by a family of Initial Value Problems associated with an Ordinary Differential Equation. Our specification has the advantage that only the observation of the temporal covariates at the time to event and the time to event itself are required to fit the model…
Nonparametric covariate adjustment is considered for log-rank type tests of treatment effect with right-censored time-to-event data from clinical trials applying covariate-adaptive randomization. Our proposed covariate-adjusted log-rank test has a simple explicit formula and a guaranteed efficiency gain over the unadjusted test. We also show that our proposed test achieves universal applicability in the sense that the same formula of test can be universally applied to simple randomization and all commonly used covariate-adaptive randomization schemes such as the stratified permuted block and P…
Response-adaptive designs have been extensively studied and used in clinical trials. However, there is a lack of a comprehensive study of response-adaptive designs that include covariates, despite their importance in clinical experiments. Because the allocation scheme and the estimation of parameters are affected by both the responses and the covariates, covariate-adjusted response-adaptive (CARA) designs are very complex to formulate. In this paper, we overcome the technical hurdles and lay out a framework for general CARA designs for the allocation of subjects to $K (\geq 2)$ treatments. The…
In this paper, we propose a covariate-adjusted nonlinear regression model. In this model, both the response and predictors can only be observed after being distorted by some multiplicative factors. Because of nonlinearity, existing methods for the linear setting cannot be directly employed. To attack this problem, we propose estimating the distorting functions by nonparametrically regressing the predictors and response on the distorting covariate; then, nonlinear least squares estimators for the parameters are obtained using the estimated response and predictors. Root $n$-consistency and asymp…
We consider nonparametric estimation of a regression curve when the data are observed with multiplicative distortion which depends on an observed confounding variable. We suggest several estimators, ranging from a relatively simple one that relies on restrictive assumptions usually made in the literature, to a sophisticated piecewise approach that involves reconstructing a smooth curve from an estimator of a constant multiple of its absolute value, and which can be applied in much more general scenarios. We show that, although our nonparametric estimators are constructed from predictors of the…
There is a surge in medical follow-up studies that include longitudinal covariates in the modeling of survival data. So far, the focus has been largely on right-censored survival data. We consider survival data that are subject to both left truncation and right censoring. Left truncation is well known to produce biased sample. The sampling bias issue has been resolved in the literature for the case which involves baseline or time-varying covariates that are observable. The problem remains open, however, for the important case where longitudinal covariates are present in survival models. A join…
In this article, we propose a new method for analyzing longitudinal data which contain responses that are missing at random. This method consists in solving the generalized estimating equation (GEE) of Liang and Zeger (1986) in which the incomplete responses are replaced by values adjusted using the inverse probability weights proposed in Yi, Ma and Carroll (2012). We show that the root estimator is consistent and asymptotically normal, essentially under the some conditions on the marginal distribution and the surrogate correlation matrix as those presented in Xie and Yang (2003) in the case o…
Fisher's randomization test (FRT) delivers exact $p$-values under the strong null hypothesis of no treatment effect on any units whatsoever and allows for flexible covariate adjustment to improve the power. Of interest is whether the procedure could also be valid for testing the weak null hypothesis of zero average treatment effect. Towards this end, we evaluate two general strategies for FRT with covariate-adjusted test statistics: that based on the residuals from an outcome model with only the covariates, and that based on the output from an outcome model with both the treatment and the cova…
Sliced inverse regression (Duan and Li [Ann. Statist. 19 (1991) 505-530], Li [J. Amer. Statist. Assoc. 86 (1991) 316-342]) is an appealing dimension reduction method for regression models with multivariate covariates. It has been extended by Ferré and Yao [Statistics 37 (2003) 475-488, Statist. Sinica 15 (2005) 665-683] and Hsing and Ren [Ann. Statist. 37 (2009) 726-755] to functional covariates where the whole trajectories of random functional covariates are completely observed. The focus of this paper is to develop sliced inverse regression for intermittently and sparsely measured longitudin…
The relationship between a time-dependent covariate and survival times is usually evaluated via the Cox model. Time-dependent covariates are generally available as longitudinal data collected regularly during the course of the study. A frequent problem, however, is the occurence of missing covariate data. A recent approach to estimation in the Cox model in this case jointly models survival and the longitudinal covariate. However, theoretical justification of this approach is still lacking. In this paper we prove existence and consistency of the maximum likelihood estimators in a joint model. T…
Measurement errors usually arise during the longitudinal data collection process. Ignoring the effects of measurement errors will lead to invalid estimates. The Lifestyle Education for Activity and Nutrition (LEAN) study was designed to assess the effectiveness of intervention for enhancing weight loss over nine months. The covariates systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at baseline, month 4, and month 9. At each assessment time, there were two replicate measurements for SBP and DBP. The replicate measurement errors of SBP follow different distribution…
A standard assumption for causal inference about the joint effects of time-varying treatment is that one has measured sufficient covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values, also known as "sequential randomization assumption (SRA)". SRA is often criticized as it requires one to accurately measure all confounders. Realistically, measured covariates can rarely capture all confounders with certainty. Often covariate measurements are at best proxies of confounders, thus invalidating inferences under SRA. In this paper, we extend the…
We carry out ANOVA comparisons of multiple treatments for longitudinal studies with missing values. The treatment effects are modeled semiparametrically via a partially linear regression which is flexible in quantifying the time effects of treatments. The empirical likelihood is employed to formulate model-robust nonparametric ANOVA tests for treatment effects with respect to covariates, the nonparametric time-effect functions and interactions between covariates and time. The proposed tests can be readily modified for a variety of data and model combinations, that encompasses parametric, semip…
