A SAS macro for the joint modeling of longitudinal outcomes and multiple competing risk dropouts

BACKGROUND AND OBJECTIVES The joint modeling of longitudinal and survival data to assess effects of multiple informative dropout mechanisms on longitudinal outcomes inference has received considerable attention during recent years; related statistical programs to apply these methods have been lacking. This paper provides a SAS macro implementation of a shared parameter model to accommodate the analysis of longitudinal outcomes in the presence of multiple competing survival/dropout events. METHODS In this macro, we assumed that the associations between the survival and the longitudinal submodels are linked through a set of shared random effects. The submodel for the longitudinal outcome takes the form of a linear mixed effects model, with specifications for the random intercept and/or random slope. The survival submodel allows up to three different competing causes for dropout, each allowing either an exponential or Weibull parametric baseline hazard function. In addition, information criterion fit statistics AIC and BIC are provided to assist with parametric baseline hazard function selection. RESULTS We illustrate the SAS Macro in a cognitive decline study sensitivity analysis using data from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). In addition, we also conduct a simulation study to show that the joint model provides unbiased parameter estimates when informative dropout exists compared against separate model approach which assumes missing at random dropout mechanisms. CONCLUSIONS We have presented a SAS macro to implement a shared parameter model for a longitudinal outcome and multiple cause-specific dropouts and made the macro code freely available for download.

[1]  Wei Liu,et al.  Analysis of Longitudinal and Survival Data: Joint Modeling, Inference Methods, and Issues , 2012 .

[2]  Gang Li,et al.  A Bayesian approach to joint analysis of longitudinal measurements and competing risks failure time data , 2007, Statistics in medicine.

[3]  Roderick J. A. Little,et al.  Modeling the Drop-Out Mechanism in Repeated-Measures Studies , 1995 .

[4]  Karen Bandeen-Roche,et al.  Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. , 2014, JAMA neurology.

[5]  Peter J. Diggle,et al.  joineR: Joint modelling of repeated measurements and time-to-event data , 2012 .

[6]  M. Albert,et al.  Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study. , 2014, American journal of epidemiology.

[7]  Yan Wang,et al.  Jointly Modeling Longitudinal and Event Time Data With Application to Acquired Immunodeficiency Syndrome , 2001 .

[8]  M D Schluchter,et al.  Methods for the analysis of informatively censored longitudinal data. , 1992, Statistics in medicine.

[9]  R. Rosenheck,et al.  Joint modelling of longitudinal outcome and interval‐censored competing risk dropout in a schizophrenia clinical trial , 2012, Journal of the Royal Statistical Society. Series A,.

[10]  Dimitris Rizopoulos,et al.  JM: An R package for the joint modelling of longitudinal and time-to-event data , 2010 .

[11]  J. Klein,et al.  Survival Analysis: Techniques for Censored and Truncated Data , 1997 .

[12]  Gang Li,et al.  Robust Joint Modeling of Longitudinal Measurements and Competing Risks Failure Time Data , 2009, Biometrical journal. Biometrische Zeitschrift.

[13]  Y. Pawitan In all likelihood : statistical modelling and inference using likelihood , 2002 .

[14]  S. Ratcliffe,et al.  Joint Modeling of Longitudinal and Survival Data via a Common Frailty , 2004, Biometrics.

[15]  A Ciampi,et al.  GFREG: a computer program for maximum likelihood regression using the Generalized F distribution. , 1985, Computer methods and programs in biomedicine.

[16]  Keith R. Abrams,et al.  Joint Modeling of Longitudinal and Survival Data , 2013 .

[17]  Naji Younes,et al.  Parametric survival models for interval-censored data with time-dependent covariates. , 2006, Biostatistics.

[18]  J. Ibrahim,et al.  A Bayesian semiparametric joint hierarchical model for longitudinal and survival data. , 2003, Biometrics.

[19]  Kaushik Ghosh,et al.  Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints , 2011, Statistics in medicine.