Intercept Estimation of Semi‐Parametric Joint Models in the Context of Longitudinal Data Subject to Irregular Observations

Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi‐parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicat...

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Published in:Biometrical journal Vol. 67; no. 6; p. e70088
Main Authors: Ledesma, Luis, Pullenayegum, Eleanor
Format: Journal Article
Language:English
Published: Germany 01.12.2025
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ISSN:0323-3847, 1521-4036, 1521-4036
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Abstract Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi‐parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicative link function. Semi‐parametric joint models define an intercept function as the mean outcome when all covariates are set to zero; this is differenced out in the course of estimation and is consequently not estimated. The Sun estimator thus provides estimates of relative covariate effects, but is unable to provide estimates of absolute effects or of longitudinal prognosis in the absence of covariates. We extend the Sun model by additionally estimating the intercept term, showing that our extended estimator is consistent and asymptotically Normal. In simulations, our estimator outperforms the original Sun estimator in terms of bias and standard error and is also more computationally efficient. We apply our estimator to a longitudinal study of tumor recurrence among bladder cancer patients. Provided the intercept term can be adequately captured using splines, we recommend that our extended Sun estimator be used in place of the original estimator, since it leads to smaller bias, smaller standard errors, and allows estimation of the mean outcome trajectories.
AbstractList Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi-parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicative link function. Semi-parametric joint models define an intercept function as the mean outcome when all covariates are set to zero; this is differenced out in the course of estimation and is consequently not estimated. The Sun estimator thus provides estimates of relative covariate effects, but is unable to provide estimates of absolute effects or of longitudinal prognosis in the absence of covariates. We extend the Sun model by additionally estimating the intercept term, showing that our extended estimator is consistent and asymptotically Normal. In simulations, our estimator outperforms the original Sun estimator in terms of bias and standard error and is also more computationally efficient. We apply our estimator to a longitudinal study of tumor recurrence among bladder cancer patients. Provided the intercept term can be adequately captured using splines, we recommend that our extended Sun estimator be used in place of the original estimator, since it leads to smaller bias, smaller standard errors, and allows estimation of the mean outcome trajectories.Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi-parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicative link function. Semi-parametric joint models define an intercept function as the mean outcome when all covariates are set to zero; this is differenced out in the course of estimation and is consequently not estimated. The Sun estimator thus provides estimates of relative covariate effects, but is unable to provide estimates of absolute effects or of longitudinal prognosis in the absence of covariates. We extend the Sun model by additionally estimating the intercept term, showing that our extended estimator is consistent and asymptotically Normal. In simulations, our estimator outperforms the original Sun estimator in terms of bias and standard error and is also more computationally efficient. We apply our estimator to a longitudinal study of tumor recurrence among bladder cancer patients. Provided the intercept term can be adequately captured using splines, we recommend that our extended Sun estimator be used in place of the original estimator, since it leads to smaller bias, smaller standard errors, and allows estimation of the mean outcome trajectories.
Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi‐parametric joint models that account for this dependence have been proposed; among these, the Sun model is the most suitable for count data as it employs a multiplicative link function. Semi‐parametric joint models define an intercept function as the mean outcome when all covariates are set to zero; this is differenced out in the course of estimation and is consequently not estimated. The Sun estimator thus provides estimates of relative covariate effects, but is unable to provide estimates of absolute effects or of longitudinal prognosis in the absence of covariates. We extend the Sun model by additionally estimating the intercept term, showing that our extended estimator is consistent and asymptotically Normal. In simulations, our estimator outperforms the original Sun estimator in terms of bias and standard error and is also more computationally efficient. We apply our estimator to a longitudinal study of tumor recurrence among bladder cancer patients. Provided the intercept term can be adequately captured using splines, we recommend that our extended Sun estimator be used in place of the original estimator, since it leads to smaller bias, smaller standard errors, and allows estimation of the mean outcome trajectories.
Author Pullenayegum, Eleanor
Ledesma, Luis
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Cites_doi 10.1002/sim.9727
10.1007/s10255-011-0037-2
10.1198/016214501753209031
10.1111/biom.13285
10.1201/9780429246593
10.1177/0962280214536537
10.1111/j.1541-0420.2008.01104.x
10.1214/aos/1176345976
10.1093/aje/kwp353
10.1093/oso/9780198524847.001.0001
10.1007/978-1-4613-3030-1_74
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semi‐parametric models
irregular observation
longitudinal data
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References Liang Y. (e_1_2_9_9_1) 2009; 65
Byar D. (e_1_2_9_4_1) 1980
Andersen P. K. (e_1_2_9_2_1) 1982; 10
Buzkova P. (e_1_2_9_3_1) 2010; 171
Hall A. (e_1_2_9_8_1) 2005
Coulombe J. (e_1_2_9_5_1) 2021; 77
Sun L. (e_1_2_9_12_1) 2011; 27
Wang M.‐C. (e_1_2_9_13_1) 2001; 96
Pullenayegum E. M. (e_1_2_9_10_1) 2023; 42
Diggle P. J. (e_1_2_9_6_1) 2002
Pullenayegum E. M. (e_1_2_9_11_1) 2016; 25
Efron B. (e_1_2_9_7_1) 1994
References_xml – volume: 42
  start-page: 2361
  issue: 14
  year: 2023
  ident: e_1_2_9_10_1
  article-title: Causal Inference With Longitudinal Data Subject to Irregular Assessment Times
  publication-title: Statistics in Medicine
  doi: 10.1002/sim.9727
– volume-title: Generalized Method of Moments
  year: 2005
  ident: e_1_2_9_8_1
– volume: 27
  start-page: 29
  issue: 1
  year: 2011
  ident: e_1_2_9_12_1
  article-title: Semiparametric Analysis of Longitudinal Data With Informative Observation Times
  publication-title: Acta Mathematicae Applicatae Sinica, English Series
  doi: 10.1007/s10255-011-0037-2
– volume: 96
  start-page: 1057
  issue: 455
  year: 2001
  ident: e_1_2_9_13_1
  article-title: Analyzing Recurrent Event Data With Informative Censoring
  publication-title: Journal of the American Statistical Association
  doi: 10.1198/016214501753209031
– volume: 77
  start-page: 162
  issue: 1
  year: 2021
  ident: e_1_2_9_5_1
  article-title: Weighted Regression Analysis to Correct for Informative Monitoring Times and Confounders in Longitudinal Studies
  publication-title: Biometrics
  doi: 10.1111/biom.13285
– volume-title: An Introduction to the Bootstrap
  year: 1994
  ident: e_1_2_9_7_1
  doi: 10.1201/9780429246593
– volume: 25
  start-page: 2992
  issue: 6
  year: 2016
  ident: e_1_2_9_11_1
  article-title: Longitudinal data subject to Irregular Observation: A Review of Methods With a Focus on Visit Processes, Assumptions, and Study Design
  publication-title: Statistical Methods in Medical Research
  doi: 10.1177/0962280214536537
– volume: 65
  start-page: 377
  issue: 2
  year: 2009
  ident: e_1_2_9_9_1
  article-title: Joint Modeling and Analysis of Longitudinal Data With Informative Observation Times
  publication-title: Biometrics
  doi: 10.1111/j.1541-0420.2008.01104.x
– volume: 10
  start-page: 1100
  issue: 4
  year: 1982
  ident: e_1_2_9_2_1
  article-title: Cox's Regression Model for Counting Processes: a Large Sample Study
  publication-title: The Annals of Statistics
  doi: 10.1214/aos/1176345976
– volume: 171
  start-page: 189
  issue: 2
  year: 2010
  ident: e_1_2_9_3_1
  article-title: Longitudinal Data Analysis for Generalized Linear Models Under Participant‐Driven Informative Follow‐Up: an Application in Maternal Health Epidemiology
  publication-title: American Journal of Epidemiology
  doi: 10.1093/aje/kwp353
– volume-title: Analysis of Longitudinal Data
  year: 2002
  ident: e_1_2_9_6_1
  doi: 10.1093/oso/9780198524847.001.0001
– start-page: 363
  volume-title: Bladder Tumors and Other Topics in Urological Oncology
  year: 1980
  ident: e_1_2_9_4_1
  doi: 10.1007/978-1-4613-3030-1_74
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Snippet Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi‐parametric joint models...
Longitudinal data are often subject to irregular visiting times, with outcomes and visit times influenced by a latent variable. Semi-parametric joint models...
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SubjectTerms Biometry - methods
Humans
Longitudinal Studies
Models, Statistical
Urinary Bladder Neoplasms
Title Intercept Estimation of Semi‐Parametric Joint Models in the Context of Longitudinal Data Subject to Irregular Observations
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