Errors-in-Variables Modeling of Personalized Treatment-Response Trajectories

Abstract
Estimating the impact of a treatment on a given response is needed in many biomedical applications. However, methodology is lacking for the case when the response is a continuous temporal curve, treatment covariates suffer extensively from measurement error, and even the exact timing of the treatments is unknown. We introduce a novel method for this challenging scenario. We model personalized treatment-response curves as a combination of parametric response functions, hierarchically sharing information across individuals, and a sparse Gaussian process for the baseline trend. Importantly, our model accounts for errors not only in treatment covariates, but also in treatment timings, a problem arising in practice for example when data on treatments are based on user self-reporting. We validate our model with simulated and real patient data, and show that in a challenging application of estimating the impact of diet on continuous blood glucose measurements, accounting for measurement error significantly improves estimation and prediction accuracy.
Funding Information
  • Business Finland (884/31/2018)
  • Academy of Finland (286607, 294015)
  • Suomen Lääketieteen Säätiö
  • Academy of Finland (314383, 266286)
  • Academy of Finland Centre of Excellence in Research on Mitochondria, Metabolism and Disease (272376)
  • Suomen Lääketieteen Säätiö
  • Gyllenberg Foundation, the Novo Nordisk Foundation (NNF17OC0027232, NNF10OC1013354)
  • Diabetestutkimussäätiö
  • Sydäntutkimussäätiö
  • University of Helsinki and Helsinki University Hospital