A latent gaussian joint modelling of multivariate longitudinal and mixture cure outcomes with application to aortic valve replacement surgery data
Main Article Content
Abstract
This study examined the effects of different association structures and multivariate longitudinal trajectories, including linear, quadratic and spline functions, on the estimation of time to event and cure proportion under the latent Gaussian model approach with application aortic valve replacement surgery data. The Bayesian framework assumed inverse-Wishart prior distribution for the covariance matrix of the random effects and Gaussian priors for the joint model fixed effects, while the penalised complexity prior was assumed for the Weibull shape parameters of the baseline hazard function. Posterior distributions were evaluated using Integrated Laplace approximation. The modelling approach was applied to aortic valve replacement surgery data to assess the effects of covariates on three longitudinal biomakers on risk of death as well as prediction of cure proportion. Spline trajectories for the multivariate longitudinal biomakers with current slope association was the best fit for the data. The full conditional distribution of latent incidence variable predicted a cure proportion of 36.33% and type of treatment valve with gender of patients were significant in the proportion of cure, risk of death and longitudinal outcomes. The probability of cure depended on the type of implanted aortic prosthesis and gender of patients.
Article Details

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
References
1. Alafchi, B., Mahjub, H., Tapak, L., Roshanaei,G. & Amirzargar, M.A.Two-Stage Joint Model for Multivariate Longitudinal and Multistate Processes, with Application to Renal Transplantation Data. Journal of Probability and Statistics Volume 2021, Article ID 6641602, 10 (20210 https://doi.org/10.1155/2021/6641602
2. Alsefri, M., Sudell, M., García-Fiñana, M., & Kolamunnage-Dona, R. Bayesian joint modelling of longitudinal and time to event data: a methodological review. BMC Medical Research Methodology, 20(1), 94 (2020). https://doi.org/10.1186/s12874-020-00976-2
3. Alvares, D., van Niekerk, J., Krainski, E. T., Rue, H. & Rustand, D. Bayesian survival analysis with INLA. Statistics in Medicine, 1–36 (2024). DOI: 10.1002/sim.10160
4. Blangiardo M. & Cameletti M. Spatial and Spatio-temporal Bayesian Models with R –INLA. John Wiley & Sons, Chichester, (2015). DOI:10.1002/9781118950203.
5. Chen M.H, Ibrahim J.G, & Sinha D. A new joint model for longitudinal and survival data with a cure fraction. J Multivar Anal 91(1):18–34 (2004). https://doi.org/10.1016/j.jmva.2004.04.005
6. Chi, Y. Y., & Ibrahim, J. G. Bayesian approaches to joint longitudinal and survival models accommodating both zero and nonzero cure fractions. Statistica Sinica, 17(2), pp. 445–462 (2007).
7. Cox, D. R. Regression Models and Life‐Tables. Journal of the Royal Statistical Society: Series B (Methodological), 34(2), pp. 187–202 (1972). https://doi.org/10.1111/j.2517-6161.1972.tb00899.x
8. Ekong, A., Olayiwola, M., Dawodu, A., & Osinuga, A. Latent Gaussian Approach to Joint Modelling of Longitudinal and Mixture Cure Outcomes. Computational Journal of Mathematical and Statistical Sciences, 4(1), 72-95 (2025). http://doi: 10.21608/cjmss.2024.303748.1061
9. Gómez-Rubio, V. Bayesian Inference with INLA. Chapman and Hall/CRC. (2020). https://doi.org/10.1201/9781315175584
10. He, B., & Luo, S. Joint modeling of multivariate longitudinal measurements and survival data with applications to Parkinson's disease. Statistical methods in medical research, 25(4), 1346–1358 (2016). https://doi.org/10.1177/0962280213480877
11. Hickey, G. L., Philipson, P., Jorgensen, A., & Kolamunnage-Dona, R. Joint Models of Longitudinal and Time-to-Event Data with More Than One Event Time Outcome: A Review. The International Journal of Biostatistics, 14(1) (2018a). https://doi.org/10.1515/ijb-2017-0047
12. Hickey, G. L., Philipson, P., Jorgensen, A., & Kolamunnage-Dona, R. JoineRML: A joint model and software package for time-to-event and multivariate longitudinal outcomes. BMC Medical Research Methodology, 18(1), 1–14 (2018b). https://doi.org/10.1186/s12874-018-0502-1
13. Kalbfleisch, J. D., & Prentice, R. L. The Statistical Analysis of Failure Time Data. Wiley. (2002). https://doi.org/10.1002/9781118032985
14. Lázaro, E., Armero, C., & Gómez-Rubio, V. Approximate Bayesian inference for mixture cure models. Test, 29(3), 750–767 (2020). https://doi.org/10.1007/s11749-019-00679-x
15. Li, N., Liu, Y., Li, S., Elashoff, R. M., & Li, G. A flexible joint model for multiple longitudinal biomarkers and a time-to-event outcome: With applications to dynamic prediction using highly correlated biomarkers. Biometrical journal. Biometrische Zeitschrift, 63(8), 1575–1586 (2021). https://doi.org/10.1002/bimj.202000085
16. Lim, E., Ali, A., Theodorou, P., Sousa, I., Ashrafian, H., Chamageorgakis, T., Duncan, A., Henein, M., Diggle, P., & Pepper, J. Longitudinal study of the profile and predictors of left ventricular mass regression after stentless aortic valve replacement. The Annals of thoracic surgery, 85(6), 2026–2029 (2008). https://doi.org/10.1016/j.athoracsur.2008.02.023
17. Martins, R., Silva, G. L., & Andreozzi, V. Joint analysis of longitudinal and survival AIDS data with a spatial fraction of long‐term survivors: A Bayesian approach. Biometrical Journal, 59(6), 1166–1183 (2017). https://doi.org/10.1002/bimj.201600159
18. Mayer, F. P., Sant’Ana, R., & Ribeiro Junior, P. J. MODELAGEM DA ESTRUTURA TEMPORAL DE CAPTURAS INCIDENTAIS EM PESCARIAS COMERCIAIS ATRAVÉS DE MODELOS HIERÁRQUICOS BAYESIANOS. Brazilian Journal of Biometrics, 37(4), 446–466 (2019). https://doi.org/10.28951/rbb.v37i4.417
19. Medina-Olivares, V., Calabrese, R., Crook, J., & Lindgren, F. Joint models for longitudinal and discrete survival data in credit scoring. European Journal of Operational Research, 307(3), 1457–1473 (2023a). https://doi.org/10.1016/J.EJOR.2022.10.022
20. Medina-Olivares, V., Lindgren, F., Calabrese, R., & Crook, J. Joint models of multivariate longitudinal outcomes and discrete survival data with INLA: An application to credit repayment behaviour. European Journal of Operational Research, 310(2), 860–873 (2023b). https://doi.org/10.1016/j.ejor.2023.03.012
21. Murray, J. & Philipson, P. A fast approximate EM algorithm for joint models of survival and multivariate longitudinal data. Computational Statistics and Data Analysis 170, 107438 (2020). https://doi.org/10.1016/j.csda.2022.107438
22. Oliveira, M. H., Abosamak, M. F., Michael Henry, B., W Benoit, S., Lippi, G., & Previdelli, I. Longitudinal serum chloride as a marker for poor prognosis in severely ill COVID-19 patients: A joint model approach. Brazilian Journal of Biometrics, 42(1), 88–99 (2024). https://doi.org/10.28951/bjb.v42i1.670
23. Opitz T. Latent Gaussian modeling and INLA: A review with focus on space-time applications. Journal of the French Statistical Society 158(3), 62-85 (2017). https://www.numdam.org/item/JSFS_2017__158_3_62_0/
24. Peng, Y., & Taylor, J. M. G. Cure Models. In Handbook of Survival Analysis, 113–134 (2014). https://doi.org/10.1201/b16248
25. Philipson, P., Hickey, G. L., Crowther, M. J. & Kolamunnage-Dona, R. Faster Monte Carlo estimation of joint models for time-to-event and multivariate longitudinal data. Computational Statistics and Data Analysis 151, 107010 (2020). https://doi.org/10.1016/j.csda.2020.107010
26. Rue, H., & Held, L. Gaussian Markov Random Fields. Chapman and Hall/CRC. (2005). https://doi.org/10.1201/9780203492024
27. Rue, H., Martino, S., & Chopin, N. Approximate Bayesian inference for latent Gaussian models by using integrated nested Laplace approximations. Journal of the Royal Statistical Society. Series B: Statistical Methodology, 71(2), 319–392 (2009) https://doi.org/10.1111/J.1467-9868.2008.00700.X
28. Rustand, D., van Niekerk, J., Rue, H., Tournigand, C., Rondeau, V., & Briollais, L. Bayesian estimation of two‐part joint models for a longitudinal semicontinuous biomarker and a terminal event with INLA: Interests for cancer clinical trial evaluation. Biometrical Journal, 65(4) (2023). https://doi.org/10.1002/bimj.202100322
29. Rustand, D., van Niekerk, J., Krainski, E. T., Rue, H., & Proust-Lima, C. Fast and flexible inference for joint models of multivariate longitudinal and survival data using integrated nested Laplace approximations. Biostatistics, 2024, 25 (2) pp. 429–448 (2024a). https://doi.org/10.1093/biostatistics/kxad019
30. Rustand, D., van Niekerk, J., Krainski, E. T., & Rue, H. Joint Modeling of Multivariate Longitudinal and Survival Outcomes with the R package INLAjoint. (2024b) https://doi.org/10.48550/arXiv.2402.08335
31. Tsiatis, A. A., & Davidian, M. Joint modelling of longitudinal and time-to-event data: An overview. Statistica Sinica, 14(3), 809–834 (2004). https://www3.stat.sinica.edu.tw/statistica/j14n3/j14n39/j14n39.html
32. van Niekerk, J., Bakka, H., & Rue, H. Joint models as latent Gaussian models - not reinventing the wheel. (2019). http://arxiv.org/abs/1901.09365
33. van Niekerk, J., Bakka, H., & Rue, H. Competing risks joint models using R-INLA. Statistical Modelling, 21(1–2), 56–71 (2021). https://doi.org/10.1177/1471082X20913654
34. Yu, M., Taylor, J. M. G., & Sandler, H. M. Individual Prediction in Prostate Cancer Studies Using a Joint Longitudinal Survival–Cure Model. Journal of the American Statistical Association, 103(481), pp. 178–187 (2008). https://doi.org/10.1198/016214507000000400