A workflow for the joint modeling of longitudinal and event data in the development of therapeutics: Tools, statistical methods, and diagnostics

CPT Pharmacometrics Syst Pharmacol. 2022 Apr;11(4):425-437. doi: 10.1002/psp4.12763. Epub 2022 Feb 21.


Clinical trials investigate treatment endpoints that usually include measurements of pharmacodynamic and efficacy biomarkers in early-phase studies and patient-reported outcomes as well as event risks or rates in late-phase studies. In recent years, a systematic trend in clinical trial data analytics and modeling has been observed, where retrospective data are integrated into a quantitative framework to prospectively support analyses of interim data and design of ongoing and future studies of novel therapeutics. Joint modeling is an advanced statistical methodology that allows for the investigation of clinical trial outcomes by quantifying the association between baseline and/or longitudinal biomarkers and event risk. Using an exemplar data set from non-small cell lung cancer studies, we propose and test a workflow for joint modeling. It allows a modeling scientist to comprehensively explore the data, build survival models, investigate goodness-of-fit, and subsequently perform outcome predictions using interim biomarker data from an ongoing study. The workflow illustrates a full process, from data exploration to predictive simulations, for selected multivariate linear and nonlinear mixed-effects models and software tools in an integrative and exhaustive manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Longitudinal Studies
  • Lung Neoplasms*
  • Models, Statistical
  • Retrospective Studies
  • Workflow


  • Biomarkers