Fitting and interpreting continuous-time latent Markov models for panel data. 2013

Jane M Lange, and Vladimir N Minin
Department of Biostatistics, University of Washington, Seattle, WA, U.S.A.

Multistate models characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses accordingly, a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration-dependent disease state sojourn distributions. We have developed a robust and efficient expectation-maximization algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data-generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a dataset of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting.

UI MeSH Term Description Entries
D008390 Markov Chains A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system. Markov Process,Markov Chain,Chain, Markov,Chains, Markov,Markov Processes,Process, Markov,Processes, Markov
D001989 Bronchiolitis Obliterans Inflammation of the BRONCHIOLES leading to an obstructive lung disease. Bronchioles are characterized by fibrous granulation tissue with bronchial exudates in the lumens. Clinical features include a nonproductive cough and DYSPNEA. Bronchiolitis, Exudative,Bronchiolitis, Proliferative,Constrictive Bronchiolitis,Exudative Bronchiolitis,Proliferative Bronchiolitis,Bronchiolitides, Constrictive,Bronchiolitides, Exudative,Bronchiolitides, Proliferative,Bronchiolitis, Constrictive,Constrictive Bronchiolitides,Exudative Bronchiolitides,Proliferative Bronchiolitides
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D005541 Forced Expiratory Volume Measure of the maximum amount of air that can be expelled in a given number of seconds during a FORCED VITAL CAPACITY determination . It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. Forced Vital Capacity, Timed,Timed Vital Capacity,Vital Capacity, Timed,FEVt,Capacities, Timed Vital,Capacity, Timed Vital,Expiratory Volume, Forced,Expiratory Volumes, Forced,Forced Expiratory Volumes,Timed Vital Capacities,Vital Capacities, Timed,Volume, Forced Expiratory,Volumes, Forced Expiratory
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D015233 Models, Statistical Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc. Probabilistic Models,Statistical Models,Two-Parameter Models,Model, Statistical,Models, Binomial,Models, Polynomial,Statistical Model,Binomial Model,Binomial Models,Model, Binomial,Model, Polynomial,Model, Probabilistic,Model, Two-Parameter,Models, Probabilistic,Models, Two-Parameter,Polynomial Model,Polynomial Models,Probabilistic Model,Two Parameter Models,Two-Parameter Model
D016040 Lung Transplantation The transference of either one or both of the lungs from one human or animal to another. Grafting, Lung,Transplantation, Lung,Graftings, Lung,Lung Grafting,Lung Graftings,Lung Transplantations,Transplantations, Lung
D018450 Disease Progression The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease

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