The goal of this study is to determine if biomarkers can be used to be predictive of renal disease progression in diabetes as a method to enrich clinical trials with patients most at risk. From the SUMMIT (Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools) programme, the authors originally identified 207 serum biomarkers that is predictive of renal function decline. From these 207 biomarkers, the authors selected 42 biomarkers using forward selection and least absolute shrinkage and selection operator (LASSO) penalized regression approaches. The 42 biomarkers were split into smaller panels and tested for the ability to predict performance similar to the larger panels.
Three separate cohorts were used to validate the smaller biomarker panels: Genetics of Diabetes Audit and Research in Tayside (GoDARTS), Swedish Scania Diabetes Registry (SDR), and the Collaborative Atorvastatin in Diabetes Study (CARDS). The multiplex Luminex panels (maximum 5 biomarkers per panel) were developed and the Luminex assays were performed by Myriad RBM. The results demonstrate that the small Luminex panels significantly improved prediction in all cohort sets.
While the increases in the AUROC (area under the receiver operating characteristic curve) are modest, individuals with the largest risk scores that includes B2M and KIM-1 can significantly enrich the expected event rate for clinical trial enrollment. The expertise of Myriad RBM in developing, manufacturing, and assaying multiplex bead-based biomarker panels is a valuable clinical partner for various clinical trial processes, including patient selection.