NCI's clinical assay development program: supporting translation of biomarkers for cancer diagnosis

This commentary illustrates the National Cancer Institute's (NCI) use of structured phased award programs (R21/R33 and later UH2/UH3 grants) to provide academic laboratories with continuous, milestone-driven funding to refine unvalidated assay prototypes into robust Laboratory Developed Test(s) (LDTs) and potentially commercialized, Food and Drug Administration (FDA)-approved In vitro Diagnostics (IVDs). Supported assays typically involve molecular or cellular biomarkers and are analytically validated in the first phase, and then clinically validated using well-annotated human biospecimens from existing studies or trials to demonstrate association with relevant clinical endpoints. These assays may test for predictive biomarkers (associated with treatment response or resistance) or prognostic biomarkers (associated with natural disease progression and patient outcomes), as long as they provide clinically useful information. Funding support through these programs has led to commercial partnerships and subsequent larger-scale clinical trials resulting in approved IVDs. These programs have also developed LDTs to serve patients with rare forms of cancer, to screen and enroll clinical trial participants for early-stage drug testing (e.g., identifying individuals whose tumors carry rare mutations that match a new drug's target), and to accelerate the clinical adoption of innovative technologies for detection and diagnosis. This commentary is organized as a perspective followed by historical examples of successful projects and concluding remarks on the requirements for rigorous diagnostics development.