Dynamic prediction of repeated events data based on landmarking model: application to colorectal liver metastases data

BMC Med Res Methodol. 2019 Feb 14;19(1):31. doi: 10.1186/s12874-019-0677-0.


Background: In some clinical situations, patients experience repeated events of the same type. Among these, cancer recurrences can result in terminal events such as death. Therefore, here we dynamically predicted the risks of repeated and terminal events given longitudinal histories observed before prediction time using dynamic pseudo-observations (DPOs) in a landmarking model.

Methods: The proposed DPOs were calculated using Aalen-Johansen estimator for the event processes described in the multi-state model. Furthermore, in the absence of a terminal event, a more convenient approach without matrix operation was described using the ordering of repeated events. Finally, generalized estimating equations were used to calculate probabilities of repeated and terminal events, which were treated as multinomial outcomes.

Results: Simulation studies were conducted to assess bias and investigate the efficiency of the proposed DPOs in a finite sample. Little bias was detected in DPOs even under relatively heavy censoring, and the method was applied to data from patients with colorectal liver metastases.

Conclusions: The proposed method enabled intuitive interpretations of terminal event settings.

Keywords: Dynamic prediction; Landmarking; Pseudo-observations; Repeated events; Terminal event.

MeSH terms

  • Algorithms*
  • Colorectal Neoplasms / secondary*
  • Computer Simulation
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / pathology*
  • Models, Theoretical*
  • Neoplasm Recurrence, Local
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data*
  • Probability
  • Proportional Hazards Models