Joint analysis of longitudinal data comprising repeated measures and times to events

In biomedical and public health research, both repeated measures of biomarkers Y as well as times T to key clinical events are often collected for a subject. The scientific question is how the distribution of the responses [T, Y|X] changes with covariates X. [T|X] may be the focus of the estimation where Y can be used as a surrogate for T. Alternatively, T may be the time to drop‐out in a study in which [Y|X] is the target for estimation. Also, the focus of a study might be on the effects of covariates X on both T and Y or on some underlying latent variable which is thought to be manifested in the observable outcomes. In this paper, we present a general model for the joint analysis of [T, Y|X] and apply the model to estimate [T|X] and other related functionals by using the relevant information in both T and Y. We adopt a latent variable formulation like that of Fawcett and Thomas and use it to estimate several quantities of clinical relevance to determine the efficacy of a treatment in a clinical trial setting. We use a Markov chain Monte Carlo algorithm to estimate the model's parameters. We illustrate the methodology with an analysis of data from a clinical trial comparing risperidone with a placebo for the treatment of schizophrenia.

[1]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .

[2]  S W Lagakos,et al.  A stochastic model for censored-survival data in the presence of an auxiliary variable. , 1976, Biometrics.

[3]  U. RajBhandary,et al.  Mapping and cloning of Neurospora crassa mitochondrial transfer RNA genes. , 1979, The Journal of biological chemistry.

[4]  Raymond J. Carroll,et al.  Estimation and comparison of changes in the presence of informative right censoring by modeling the censoring process , 1988 .

[5]  P. Diggle An approach to the analysis of repeated measurements. , 1988, Biometrics.

[6]  R. Prentice Surrogate endpoints in clinical trials: definition and operational criteria. , 1989, Statistics in medicine.

[7]  P. McCullagh,et al.  Generalized Linear Models, 2nd Edn. , 1990 .

[8]  David R. Cox,et al.  Role of Models in Statistical Analysis , 1990 .

[9]  Scott L. Zeger,et al.  Generalized linear models with random e ects: a Gibbs sampling approach , 1991 .

[10]  Richard H. Jones Longitudinal data with serial correlation , 1993 .

[11]  Mitchell H. Gail,et al.  AIDS Epidemiology: A Quantitative Approach , 1994 .

[12]  M S Pepe,et al.  Surrogate and auxiliary endpoints in clinical trials, with potential applications in cancer and AIDS research. , 1994, Statistics in medicine.

[13]  M. Kenward,et al.  Informative Drop‐Out in Longitudinal Data Analysis , 1994 .

[14]  M. Kenward,et al.  Informative dropout in longitudinal data analysis (with discussion) , 1994 .

[15]  Nan M. Laird,et al.  Multivariate Logistic Models for Incomplete Binary Responses , 1996 .

[16]  D. Thomas,et al.  Simultaneously modelling censored survival data and repeatedly measured covariates: a Gibbs sampling approach. , 1996, Statistics in medicine.

[17]  N M Laird,et al.  Model-based approaches to analysing incomplete longitudinal and failure time data. , 1997, Statistics in medicine.

[18]  N M Laird,et al.  Mixture models for the joint distribution of repeated measures and event times. , 1997, Statistics in medicine.

[19]  M J Daniels,et al.  Meta-analysis for the evaluation of potential surrogate markers. , 1997, Statistics in medicine.

[20]  M. Wulfsohn,et al.  A joint model for survival and longitudinal data measured with error. , 1997, Biometrics.

[21]  B. Everitt,et al.  Analysis of longitudinal data , 1998, British Journal of Psychiatry.

[22]  P. Heagerty Marginally Specified Logistic‐Normal Models for Longitudinal Binary Data , 1999, Biometrics.

[23]  Scott L. Zeger,et al.  Marginalized Multilevel Models and Likelihood Inference , 2000 .

[24]  S L Zeger,et al.  The Evaluation of Multiple Surrogate Endpoints , 2001, Biometrics.

[25]  Eric R. Ziegel,et al.  Generalized Linear Models , 2002, Technometrics.

[26]  Nicole A. Lazar,et al.  Statistical Analysis With Missing Data , 2003, Technometrics.