Prognostic assessment of repeatedly measured time-dependent biomarkers, with application to dilated cardiomyopathy

We propose new time-dependent sensitivity, specificity, ROC curves and net reclassification indices that can take into account biomarkers or scores that are repeatedly measured at different time-points. Inference proceeds through inverse probability weighting and resampling. The newly proposed measures exploit the information contained in biomarkers measured at different visits, rather than using only the measurements at the first visits. The contribution is illustrated via simulations and an original application on patients affected by dilated cardiomiopathy. The aim is to evaluate if repeated binary measurements of right ventricular dysfunction bring additive prognostic information on mortality/urgent heart transplant. It is shown that taking into account the trajectory of the new biomarker improves risk classification, while the first measurement alone might not be sufficiently informative. The methods are implemented in an R package (longROC), freely available on CRAN.