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 distributions, as does DBP. To account for the distributional difference of replicate measurement errors, a new method for analyzing longitudinal data with replicate covariate measurement errors is developed based on the empirical likelihood method. The asymptotic properties of the proposed estimator are established under some regularity conditions. The confidence region for the parameters of interest can be constructed based on the chi-squared approximation without estimating the covariance matrix. Additionally, the proposed empirical likelihood estimator is asymptotically more efficient than the estimator of Lin et al. (2018). Extensive simulations demonstrate that the proposed method can eliminate the effects of measurement errors in the covariate and has a high estimation efficiency. The proposed method indicates the significant effect of the intervention on BMI in the LEAN study.
Construction of valid statistical inference for estimators based on data-driven selection has received a lot of attention in the recent times. Berk et al. (2013) is possibly the first work to provide valid inference for Gaussian homoscedastic linear regression with fixed covariates under arbitrary covariate/variable selection. The setting is unrealistic and is extended by Bachoc et al. (2016) by relaxing the distributional assumptions. A major drawback of the aforementioned works is that the construction of valid confidence regions is computationally intensive. In this paper, we first prove th…
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…
Cluster randomized trials (CRTs) are a popular design to study the effect of interventions in infectious disease settings. However, standard analysis of CRTs primarily relies on strong parametric methods, usually mixed-effect models to account for the clustering structure, and focuses on the overall intent-to-treat (ITT) effect to evaluate effectiveness. The paper presents two assumption-lean methods to analyze two types of effects in CRTs, ITT effects and network effects among well-known compliance groups. For the ITT effects, we study the overall and the heterogeneous ITT effects among the o…
On a penalised likelihood approach for joint modelling of longitudinal covariates and partly interval-censored data -- an application to the Anti-PD1 brain collaboration trial
Longitudinal study designs are indispensable for studying disease progression. Inferring covariate effects from longitudinal data, however, requires interpretable methods that can model complicated covariance structures and detect nonlinear effects of both categorical and continuous covariates, as well as their interactions. Detecting disease effects is hindered by the fact that they often occur rapidly near the disease initiation time, and this time point cannot be exactly observed. An additional challenge is that the effect magnitude can be heterogeneous over the subjects. We present lgpr, a…
In longitudinal data a response variable is measured over time, or under different conditions, for a cohort of individuals. In many situations all intended measurements are not available which results in missing values. If the missing value is never followed by an observed measurement, this leads to dropout pattern. The missing values could be in the response variable, the covariates or in both. The missingness mechanism is termed non-random when the probability of missingness depends on the missing value and may be on the observed values. In this case the missing values should be considered i…
Predicting patient survival probabilities based on observed covariates is an important assessment in clinical practice. These patient-specific covariates are often measured over multiple follow-up appointments. It is then of interest to predict survival based on the history of these longitudinal measurements, and to update predictions as more observations become available. The standard approaches to these so-called `dynamic prediction' assessments are joint models and landmark analysis. Joint models involve high-dimensional parametrisations, and their computational complexity often prohibits i…
We are interested in survival analysis of hemodialysis patients for whom several biomarkers are recorded over time. Motivated by this challenging problem, we propose a general framework for multivariate joint longitudinal-survival modeling that can be used to examine the association between several longitudinally recorded covariates and a time-to-event endpoint. Our method allows for simultaneous modeling of longitudinal covariates by taking their correlation into account. This leads to a more efficient method for modeling their trajectories over time, and hence, it can better capture their re…
Joint models for a wide class of response variables and longitudinal measurements consist on a mixed-effects model to fit longitudinal trajectories whose random effects enter as covariates in a generalized linear model for the primary response. They provide a useful way to asses association between these two kinds of data, which in clinical studies are often collected jointly on a series of individuals and may help understanding, for instance, the mechanisms of recovery of a certain disease or the efficacy of a given therapy. The most common joint model in this framework is based on a linear m…
Covariate Informed Identification of Heterogeneity and Outliers in Longitudinal Data
University of Louisville（路易斯维尔大学）；Case Western Reserve University（凯斯西储大学）；Mass General Brigham, Harvard Medical School（麻省总医院布里格姆医院，哈佛医学院）；University of Missouri（密苏里大学）
Multivariate longitudinal modeling of cross-sectional and lagged associations between a continuous time-varying endogenous covariate and a non-Gaussian outcome
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…
In this paper, we propose a semiparametric, tree based joint latent class modeling approach (JLCT) to model the joint behavior of longitudinal and time-to-event data. Existing joint latent class modeling approaches are parametric and can suffer from high computational cost. The most common parametric approach, the joint latent class model (JLCM), further restricts analysis to using time-invariant covariates in modeling survival risks and latent class memberships. Instead, the proposed JLCT is fast to fit, and can use time-varying covariates in all of its modeling components. We demonstrate the…
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…
While studying response trajectory, often the population of interest may be diverse enough to exist distinct subgroups within it and the longitudinal change in response may not be uniform in these subgroups. That is, the timeslope and/or influence of covariates in longitudinal profile may vary among these different subgroups. For example, Raudenbush (2001) used depression as an example to argue that it is incorrect to assume that all the people in a given population would be experiencing either increasing or decreasing levels of depression. In such cases, traditional linear mixed effects model…
The sequential treatment decisions made by physicians to treat chronic diseases are formalized in the statistical literature as dynamic treatment regimes. To date, methods for dynamic treatment regimes have been developed under the assumption that observation times, i.e., treatment and outcome monitoring times, are determined by study investigators. That assumption is often not satisfied in electronic health records data in which the outcome, the observation times, and the treatment mechanism are associated with patients' characteristics. The treatment and observation processes can lead to spu…
In many longitudinal studies, the covariate and response are often intermittently observed at irregular, mismatched and subject-specific times. How to deal with such data when covariate and response are observed asynchronously is an often raised problem. Bayesian Additive Regression Trees(BART) is a Bayesian non-Parametric approach which has been shown to be competitive with the best modern predictive methods such as random forest and boosted decision trees. The sum of trees structure combined with a Bayesian inferential framework provide a accurate and robust statistic method. BART variant so…
In various data situations joint models are an efficient tool to analyze relationships between time dependent covariates and event times or to correct for event-dependent dropout occurring in regression analysis. Joint modeling connects a longitudinal and a survival submodel within a single joint likelihood which then can be maximized by standard optimization methods. Main burdens of these conventional methods are that the computational effort increases rapidly in higher dimensions and they do not offer special tools for proper variable selection. Gradient boosting techniques are well known am…
In this paper, we propose a general subgroup analysis framework based on semiparametric additive mixed effect models in longitudinal analysis, which can identify subgroups on each covariate and estimate the corresponding regression functions simultaneously. In addition, the proposed procedure is applicable for both balanced and unbalanced longitudinal data. A backfitting combined with k-means algorithm is developed to estimate each semiparametric additive component across subgroups and detect subgroup structure on each covariate respectively. The actual number of groups is estimated by minimiz…
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…
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…
We propose a Bayesian inference approach for a class of latent Markov models. These models are widely used for the analysis of longitudinal categorical data, when the interest is in studying the evolution of an individual unobservable characteristic. We consider, in particular, the basic latent Markov, which does not account for individual covariates, and its version that includes such covariates in the measurement model. The proposed inferential approach is based on a system of priors formulated on a transformation of the initial and transition probabilities of the latent Markov chain. This s…
Generalized Estimation Equations (GEE) are a well-known method for the analysis of categorical longitudinal responses. GEE method has computational simplicity and population parameter interpretation. In the presence of missing data it is only valid under the strong assumption of missing completely at random. A doubly robust estimator (DRGEE) for correlated ordinal longitudinal data is a nice approach for handling intermittently missing response and covariate under the MAR mechanism. Independent working correlation is the standard way in DRGEE. However, when covariate is not time stationary, ef…
In recent years, longitudinal neuroimaging study has become increasingly popular in neuroscience research to investigate disease-related changes in brain functions. In current neuroscience literature, one of the most commonly used tools to extract and characterize brain functional networks is independent component analysis (ICA). However, existing ICA methods are not suited for modelling repeatedly measured imaging data. In this paper, we propose a novel longitudinal independent component model (L-ICA) which provides a formal modeling framework for extending ICA to longitudinal studies. By inc…
Longitudinal Random Forests for Sparse and Irregular Response Trajectories
Department of Mathematics and Statistics, Binghamton University（数学与统计学系，宾夕法尼亚大学伯灵顿分校）；Department of Mathematics, Illinois State University（数学系，伊利诺伊州立大学）；Department of Biostatistics, The University of North Carolina at Chapel Hill（生物统计学系，北卡罗来纳大学教堂山分校）
Modeling of longitudinal data often requires diffusion models that incorporate overall time-dependent, nonlinear dynamics of multiple components and provide sufficient flexibility for subject-specific modeling. This complexity challenges parameter inference and approximations are inevitable. We propose a method for approximate maximum-likelihood parameter estimation in multivariate time-inhomogeneous diffusions, where subject-specific flexibility is accounted for by incorporation of multidimensional mixed effects and covariates. We consider $N$ multidimensional independent diffusions $X^i = (X…
In immunological and clinical studies, matrix-valued time-series data clustering is increasingly popular. Researchers are interested in finding low-dimensional embedding of subjects based on potentially high-dimensional longitudinal features and investigating relationships between static clinical covariates and the embedding. These studies are often challenging due to high dimensionality, as well as the sparse and irregular nature of sample collection along the time dimension. We propose a smoothed probabilistic PARAFAC model with covariates (SPACO) to tackle these two problems while utilizing…
We propose a M-quantile regression model for the analysis of multivariate, continuous, longitudinal data. M-quantile regression represents an appealing alternative to standard regression models, as it combines the robustness of quantile and the efficiency of expectile regression, providing a complete picture of the response variable distribution. Discrete, individual-specific, random parameters are used to account for both dependence within the same response recorded at different times and association between different responses observed on the same sample unit at a given time. A suitable para…
Many high dimensional and high-throughput biological datasets have complex sample correlation structures, which include longitudinal and multiple tissue data, as well as data with multiple treatment conditions or related individuals. These data, as well as nearly all high-throughput `omic' data, are influenced by technical and biological factors unknown to the researcher, which, if unaccounted for, can severely obfuscate estimation and inference on effects due to the known covariate of interest. We therefore developed CBCV and CorrConf: provably accurate and computationally efficient methods t…
Precision medicine incorporates patient-level covariates to tailor treatment decisions, seeking to improve outcomes. In longitudinal studies with time-varying covariates and sequential treatment decisions, precision medicine can be formalized with dynamic treatment regimes (DTRs): sequences of covariate-dependent treatment rules. To date, the precision medicine literature has not addressed a ubiquitous concern in health research - measurement error - where observed data deviate from the truth. We discuss the consequences of ignoring measurement error in the context of DTRs, focusing on challen…
We propose a novel semiparametric model for the joint distribution of a continuous longitudinal outcome and the baseline covariates using an enriched Dirichlet process (EDP) prior. This joint model decomposes into a linear mixed model for the outcome given the covariates and marginals for the covariates. The nonparametric EDP prior is placed on the regression and spline coefficients, the error variance, and the parameters governing the predictor space. We predict the outcome at unobserved time points for subjects with data at other time points as well as for new subjects with only baseline cov…
Examination of Nonlinear Longitudinal Processes with Latent Variables, Latent Processes, Latent Changes, and Latent Classes in the Structural Equation Modeling Framework: The R package nlpsem
Longitudinal processes often unfold concurrently where the growth of two or more longitudinal outcomes are associated. Additionally, if the study under investigation is long, the growth curves may exhibit nonconstant change with respect to time. Multiple existing studies have developed multivariate growth models with nonlinear functional forms to explore joint development where two longitudinal records are correlated over time. However, the relationship between multiple longitudinal outcomes may also be unidirectional. Accordingly, it is of interest to estimate regression coefficients of such …
