Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

Journal: Clinical and translational science
Published Date:

Abstract

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function.

Authors

  • Xiajing Gong
    Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
  • Meng Hu
    Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
  • Liang Zhao
    Graduate School of Advanced Integrated Studies in Human Survivability (Shishu-Kan), Kyoto University, Kyoto, Japan.