Identifying a biomarker or treatment-dose threshold that marks a specified level of risk is an important problem, especially in clinical trials. This risk, viewed as a function of thresholds and possibly adjusted for covariates, we call the threshold-response function. Extending the work of Donovan, Hudgens and Gilbert (2019), we propose a nonparametric efficient estimator for the covariate-adjusted threshold-response function, which utilizes machine learning and Targeted Minimum-Loss Estimation (TMLE). We additionally propose a more general estimator, based on sequential regression, that also applies when there is outcome missingness. We show that the threshold-response for a given threshold may be viewed as the expected outcome under a stochastic intervention where all participants are given a treatment dose above the threshold. We prove the estimator is efficient and characterize its asymptotic distribution. A method to construct simultaneous 95% confidence bands for the threshold-response function and its inverse is given. Furthermore, we discuss how to adjust our estimator when the treatment or biomarker is missing-at-random, as is the case in clinical trials with biased sampling designs, using inverse-probability-weighting. The methods are assessed in a diverse set of simulation settings with rare outcomes and cumulative case-control sampling. The methods are employed to estimate neutralizing antibody thresholds for virologically confirmed dengue risk in the CYD14 and CYD15 dengue vaccine trials.
Differences between biological networks corresponding to disease conditions can help delineate the underlying disease mechanisms. Existing methods for differential network analysis do not account for dependence of networks on covariates. As a result, these approaches may detect spurious differential connections induced by the effect of the covariates on both the disease condition and the network. To address this issue, we propose a general covariate-adjusted test for differential network analysis. Our method assesses differential network connectivity by testing the null hypothesis that the net…
In this paper we propose a general class of covariate-adjusted response-adaptive (CARA) designs based on a new functional urn model. We prove strong consistency concerning the functional urn proportion and the proportion of subjects assigned to the treatment groups, in the whole study and for each covariate profile, allowing the distribution of the responses conditioned on covariates to be estimated nonparametrically. In addition, we establish joint central limit theorems for the above quantities and the sufficient statistics of features of interest, which allow to construct procedures to make…
In this paper, we consider a weighted local linear estimator based on the inverse selection probability for nonparametric regression with missing covariates at random. The asymptotic distribution of the maximal deviation between the estimator and the true regression function is derived and an asymptotically accurate simultaneous confidence band is constructed. The estimator for the regression function is shown to be oracally efficient in the sense that it is uniformly indistinguishable from that when the selection probabilities are known. Finite sample performance is examined via simulation st…
A dimension reduction-based adaptive-to-model test is proposed for significance of a subset of covariates in the context of a nonparametric regression model. Unlike existing local smoothing significance tests, the new test behaves like a local smoothing test as if the number of covariates were just that under the null hypothesis and it can detect local alternatives distinct from the null at the rate that is only related to the number of covariates under the null hypothesis. Thus, the curse of dimensionality is largely alleviated when nonparametric estimation is inevitably required. In the case…
We investigate nonparametric regression methods based on spatial depth and quantiles when the response and the covariate are both functions. As in classical quantile regression for finite dimensional data, regression techniques developed here provide insight into the influence of the functional covariate on different parts, like the center as well as the tails, of the conditional distribution of the functional response. Depth and quantile based nonparametric regressions are useful to detect heteroscedasticity in functional regression. We derive the asymptotic behaviour of nonparametric depth a…
We consider inference for the mean and covariance functions of covariate adjusted functional data using Local Linear Kernel (LLK) estimators. By means of a double asymptotic, we differentiate between sparse and dense covariate adjusted functional data - depending on the relative order of m (the discretization points per function) and n (the number of functions). Our simulation results demonstrate that the existing asymptotic normality results can lead to severely misleading inferences in finite samples. We explain this phenomenon based on our theoretical results and propose finite-sample corre…
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…
The accuracy of a diagnostic test is typically characterised using the receiver operating characteristic (ROC) curve. Summarising indexes such as the area under the ROC curve (AUC) are used to compare different tests as well as to measure the difference between two populations. Often additional information is available on some of the covariates which are known to influence the accuracy of such measures. We propose nonparametric methods for covariate adjustment of the AUC. Models with normal errors and non-normal errors are discussed and analysed separately. Nonparametric regression is used for…
We analyze the statistical properties of nonparametric regression estimators using covariates which are not directly observable, but have be estimated from data in a preliminary step. These so-called generated covariates appear in numerous applications, including two-stage nonparametric regression, estimation of simultaneous equation models or censored regression models. Yet so far there seems to be no general theory for their impact on the final estimator's statistical properties. Our paper provides such results. We derive a stochastic expansion that characterizes the influence of the generat…
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…
In this paper, a nonparametric estimator is proposed for estimating the L1-median for multivariate conditional distribution when the covariates take values in an infinite dimensional space. The multivariate case is more appropriate to predict the components of a vector of random variables simultaneously rather than predicting each of them separately. While estimating the conditional L1-median function using the well-known Nadarya-Waston estimator, we establish the strong consistency of this estimator as well as the asymptotic normality. We also present some simulations and provide how to built…
University of Chicago（芝加哥大学）；UC Berkeley（加州大学伯克利分校）
We study covariate shift in the context of nonparametric regression. We introduce a new measure of distribution mismatch between the source and target distributions that is based on the integrated ratio of probabilities of balls at a given radius. We use the scaling of this measure with respect to the radius to characterize the minimax rate of estimation over a family of Hölder continuous functions under covariate shift. In comparison to the recently proposed notion of transfer exponent, this measure leads to a sharper rate of convergence and is more fine-grained. We accompany our theory with …
Consider the task of matrix estimation in which a dataset $X \in \mathbb{R}^{n\times m}$ is observed with sparsity $p$, and we would like to estimate $\mathbb{E}[X]$, where $\mathbb{E}[X_{ui}] = f(α_u, β_i)$ for some Holder smooth function $f$. We consider the setting where the row covariates $α$ are unobserved yet the column covariates $β$ are observed. We provide an algorithm and accompanying analysis which shows that our algorithm improves upon naively estimating each row separately when the number of rows is not too small. Furthermore when the matrix is moderately proportioned, our algorit…
The main purpose is to estimate the regression function of a real random variable with functional explanatory variable by using a recursive nonparametric kernel approach. The mean square error and the almost sure convergence of a family of recursive kernel estimates of the regression function are derived. These results are established with rates and precise evaluation of the constant terms. Also, a central limit theorem for this class of estimators is established. The method is evaluated on simulations and real data set studies.
We present a nonparametric family of estimators for the tail index of a Pareto-type distribution when covariate information is available. Our estimators are based on a weighted sum of the log-spacings between some selected observations. This selection is achieved through a moving window approach on the covariate domain and a random threshold on the variable of interest. Asymptotic normality is proved under mild regularity conditions and illustrated for some weight functions. Finite sample performances are presented on a real data study.
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…
A central goal of causal inference is to detect and estimate the treatment effects of a given treatment or intervention on an outcome variable of interest, where a member known as the heterogeneous treatment effect (HTE) is of growing popularity in recent practical applications such as the personalized medicine. In this paper, we model the HTE as a smooth nonparametric difference between two less smooth baseline functions, and determine the tight statistical limits of the nonparametric HTE estimation as a function of the covariate geometry. In particular, a two-stage nearest-neighbor-based est…
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…
Semiparametric single-index assumptions are convenient and widely used dimen\-sion reduction approaches that represent a compromise between the parametric and fully nonparametric models for regressions or conditional laws. In a mean regression setup, the SIM assumption means that the conditional expectation of the response given the vector of covariates is the same as the conditional expectation of the response given a scalar projection of the covariate vector. In a conditional distribution modeling, under the SIM assumption the conditional law of a response given the covariate vector coincide…
Adaptive deep nonparametric regression from dependent data under covariate shift
Université Jean Monnet, ICJ UMR5208, CNRS, Ecole Centrale de Lyon, INSA Lyon, Universite Claude Bernard Lyon 1（里昂 Jean Monnet 大学，ICJ UMR5208，国家科学研究中心，里昂中央理工大学，里昂国家理工学校，里昂大学 Claude Bernard 1）
This paper deals with nonparametric estimation of conditional den-sities in mixture models in the case when additional covariates are available. The proposed approach consists of performing a prelim-inary clustering algorithm on the additional covariates to guess the mixture component of each observation. Conditional densities of the mixture model are then estimated using kernel density estimates ap-plied separately to each cluster. We investigate the expected L 1 -error of the resulting estimates and derive optimal rates of convergence over classical nonparametric density classes provided the…
To maximize clinical benefit, clinicians routinely tailor treatment to the individual characteristics of each patient, where individualized treatment rules are needed and are of significant research interest to statisticians. In the covariate-adjusted randomization clinical trial with many covariates, we model the treatment effect with an unspecified function of a single index of the covariates and leave the baseline response completely arbitrary. We devise a class of estimators to consistently estimate the treatment effect function and its associated index while bypassing the estimation of th…
We study semiparametric varying-coefficient partially linear models when some linear covariates are not observed, but ancillary variables are available. Semiparametric profile least-square based estimation procedures are developed for parametric and nonparametric components after we calibrate the error-prone covariates. Asymptotic properties of the proposed estimators are established. We also propose the profile least-square based ratio test and Wald test to identify significant parametric and nonparametric components. To improve accuracy of the proposed tests for small or moderate sample size…
We consider the problem of identifying sub-groups of participants in a clinical trial that have enhanced treatment effect. Recursive partitioning methods that recursively partition the covariate space based on some measure of between groups treatment effect difference are popular for such sub-group identification. The most commonly used recursive partitioning method, the classification and regression tree algorithm, first creates a large tree by recursively partitioning the covariate space using some splitting criteria and then selects the final tree from all subtrees of the large tree. In the…
We propose generalized additive partial linear models for complex data which allow one to capture nonlinear patterns of some covariates, in the presence of linear components. The proposed method improves estimation efficiency and increases statistical power for correlated data through incorporating the correlation information. A unique feature of the proposed method is its capability of handling model selection in cases where it is difficult to specify the likelihood function. We derive the quadratic inference function-based estimators for the linear coefficients and the nonparametric function…
Determining the relevant spatial covariates is one of the most important problems in the analysis of point patterns. Parametric methods may lead to incorrect conclusions, especially when the model of interactions between points is wrong. Therefore, we propose a fully nonparametric approach to testing significance of a covariate, taking into account the possible effects of nuisance covariates. Our tests match the nominal significance level, and their powers are comparable with the powers of parametric tests in cases where both the model for intensity function and the model for interactions are …
Accurate diagnosis of disease is of fundamental importance in clinical practice and medical research. Before a medical diagnostic test is routinely used in practice, its ability to distinguish between diseased and nondiseased states must be rigorously assessed through statistical analysis. The receiver operating characteristic (ROC) curve is the most popular used tool for evaluating the discriminatory ability of continuous-outcome diagnostic tests. It has been acknowledged that several factors (e.g., subject-specific characteristics, such as age and/or gender) can affect the test's accuracy be…
We investigate testing of the hypothesis of independence between a covariate and the marks in a marked point process. It would be rather straightforward if the (unmarked) point process were independent of the covariate and the marks. In practice, however, such an assumption is questionable and possible dependence between the point process and the covariate or the marks may lead to incorrect conclusions. Therefore, we propose to investigate the complete dependence structure in the triangle points--marks--covariates together. We take advantage of the recent development of the nonparametric rando…
Covariate adjustment is an important tool in the analysis of randomized clinical trials and observational studies. It can be used to increase efficiency and thus power, and to reduce possible bias. While most statistical tests in randomized clinical trials are nonparametric in nature, approaches for covariate adjustment typically rely on specific regression models, such as the linear model for a continuous outcome, the logistic regression model for a dichotomous outcome and the Cox model for survival time. Several recent efforts have focused on model-free covariate adjustment. This paper makes…
In this paper, we present three estimators of the ROC curve when missing observations arise among the biomarkers. Two of the procedures assume that we have covariates that allow to estimate the propensity and the estimators are obtained using an inverse probability weighting method or a smoothed version of it. The other one assumes that the covariates are related to the biomarkers through a regression model which enables us to construct convolution--based estimators of the distribution and quantile functions. Consistency results are obtained under mild conditions. Through a numerical study we …
We consider nonparametric prediction with multiple covariates, in particular categorical or functional predictors, or a mixture of both. The method proposed bases on an extension of the Nadaraya-Watson estimator where a kernel function is applied on a linear combination of distance measures each calculated on single covariates, with weights being estimated from the training data. The dependent variable can be categorical (binary or multi-class) or continuous, thus we consider both classification and regression problems. The methodology presented is illustrated and evaluated on artificial and r…
We present an objective Bayes method for covariance selection in Gaussian multivariate regression models whose error term has a covariance structure which is Markov with respect to a Directed Acyclic Graph (DAG). The scope is covariate-adjusted sparse graphical model selection, a topic of growing importance especially in the area of genetical genomics (eQTL analysis). Specifically, we provide a closed-form expression for the marginal likelihood of any DAG (with small parent sets) whose computation virtually requires no subjective elicitation by the user and involves only conjugate matrix norma…
