We consider planning longitudinal covariate measurements in follow-up studies where covariates are time-varying. We assume that the entire cohort cannot be selected for longitudinal measurements due to financial limitations and study how a subset of the cohort should be selected optimally in order to obtain precise estimates of covariate effects in a survival model. In our approach, the study will be designed sequentially utilizing the data collected in previous measurements of the individuals as prior information. We propose using a Bayesian optimality criterion in the subcohort selections, which is compared with simple random sampling using simulated and real follow-up data. This study extends previous results where optimal subcohort selection was studied with only one re-measurement and one covariate, to more realistic cases where several covariates and measurement points are allowed. Our results support the conclusion that the precision of the estimates can be clearly improved by optimal design.
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…
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…
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…
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）
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…
Multivariate longitudinal modeling of cross-sectional and lagged associations between a continuous time-varying endogenous covariate and a non-Gaussian outcome
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 the attention-deficit hyperactivity disorder (ADHD) study, children are prescribed different stimulant medications. The height measurements are recorded longitudinally along with the medication time. Differences among the patients are captured by the parameters suggested the Superimposition by Translation and Rotation (SITAR) model using three subject-specific parameters to estimate their deviation from the mean growth curve. In this paper, we generalize the SITAR model in a Bayesian way with time-invariant covariates. The time-invariant model allows us to predict latent growth factors. Sin…
In longitudinal studies, subjects may be lost to follow-up, or miss some of the planned visits, leading to incomplete response sequences. When the probability of non-response, conditional on the available covariates and the observed responses, still depends on unobserved outcomes, the dropout mechanism is said to be non ignorable. A common objective is to build a reliable association structure to account for dependence between the longitudinal and the dropout processes. Starting from the existing literature, we introduce a random coefficient based dropout model where the association between ou…
Aalto University（阿尔托大学）；HUS Helsinki University Hospital（赫尔辛基大学医院）；University of Helsinki（赫尔辛基大学）
Longitudinal datasets measured repeatedly over time from individual subjects, arise in many biomedical, psychological, social, and other studies. A common approach to analyse high-dimensional data that contains missing values is to learn a low-dimensional representation using variational autoencoders (VAEs). However, standard VAEs assume that the learnt representations are i.i.d., and fail to capture the correlations between the data samples. We propose the Longitudinal VAE (L-VAE), that uses a multi-output additive Gaussian process (GP) prior to extend the VAE's capability to learn structured…
Surveys often ask respondents to report nonnegative counts, but respondents may misremember or round to a nearby multiple of 5 or 10. This phenomenon is called heaping, and the error inherent in heaped self-reported numbers can bias estimation. Heaped data may be collected cross-sectionally or longitudinally and there may be covariates that complicate the inferential task. Heaping is a well-known issue in many survey settings, and inference for heaped data is an important statistical problem. We propose a novel reporting distribution whose underlying parameters are readily interpretable as rat…
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
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…
Aalto University（阿尔托大学）；University of Helsinki（赫尔辛基大学）；Bayer Pharmaceuticals（拜耳制药）
Conditional variational autoencoders (CVAEs) are versatile deep generative models that extend the standard VAE framework by conditioning the generative model with auxiliary covariates. The original CVAE model assumes that the data samples are independent, whereas more recent conditional VAE models, such as the Gaussian process (GP) prior VAEs, can account for complex correlation structures across all data samples. While several methods have been proposed to learn standard VAEs from partially observed datasets, these methods fall short for conditional VAEs. In this work, we propose a method to …
This paper considers the problem of mismeasured categorical covariates in the context of regression modeling; if unaccounted for, such misclassification is known to result in misestimation of model parameters. Here, we exploit the fact that explicitly modeling covariate misclassification leads to a mixture representation. Assuming common parametric families for the mixture components, and assuming that the misclassification occurrence is independent of the response variable, the mixture representation permits model parameters to be identified even when misclassification probabilities are unkno…
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…
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 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…
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…
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…
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…
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…
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…
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…
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 …
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…
Penalized generalized estimating equations with Elastic Net or L2-Smoothly Clipped Absolute Deviation penalization are proposed to simultaneously select the most important variables and estimate their effects for longitudinal Gaussian data when multicollinearity is present. The method is able to consistently select and estimate the main effects even when strong correlations are present. In addition, the potential pitfall of time-dependent covariates is clarified. Both asymptotic theory and simulation results reveal the effectiveness of penalization as a data mining tool for longitudinal data, …
