Evaluating Assays in the Absence of a Gold Standard: The AZ Proteus / Matrix Studies of ctDNA

Circulating Tumor DNA (ctDNA) are fragments of DNA shed by tumor cells into the bloodstream, some having known cancer-related mutations. Several companies are developing new assays to measure ctDNA for determining cancer presence and tumor burden from plasma. The pharmaceutical developer wants to find the best value assays for use in screening for new cancer cases, drug performance during clinical trials and monitoring post-treatment status. However, there is no gold standard to compare against. Statistical issues that arise include agreement among assays, computing a common value for ease of comparisons, missing data, creating contrived samples for evaluating assays at very low concentrations, evaluating limits of detection, estimating assay variability, and estimating accuracy in measuring change, especially change due to treatment.

assay evaluation

measure agreement

limit of detection

cancer

ctDNA 

Practice and Applications

Symposium on Data Science and Statistics (SDSS) 2024