The road from discovery to clinical diagnostics: lessons learned from the first FDA-cleared in vitro diagnostic multivariate index assay of proteomic biomarkers.

BACKGROUND After more than a decade of biomarker discovery research using advanced genomic and proteomic technologies, very few biomarkers have been translated into clinical diagnostics for patient care. This has become an urgent issue to be addressed because the continuing funding from both the public and private sources are called into question. METHODS We use as an example, OVA1, the first in vitro diagnostic multivariate index assay (IVDMIA) of proteomic biomarkers recently cleared by the US FDA (Food and Drug Administration) to describe our experience through the long road from biomarker discovery, to validation, and finally to multi-institutional trial for regulatory approval by the FDA. RESULTS We discuss 3 issues that are key bridges in the path of biomarker development to actual clinical diagnostics: 1) to generate sufficient and "portable" evidence in preliminary validation studies to support investment for large-scale validation trials; 2) to carefully and clearly define clinical utility that balances desire for broad applicability and feasibility for completing clinical trials for regulatory approval; and 3) to select/develop assays with analytical performance suitable for clinical deployment. CONCLUSIONS We learned that the road from biomarker discovery, validation, to clinical diagnostics could be long and winding, and often frustrating. However, we also know that, with the right approaches, at the end of the road, there is a rainbow waiting for us. IMPACT Provide insights and recommendations for the translation of proteomic biomarkers into clinical diagnostics.