An In Vitro Diagnostic Multivariate Index Assay (IVDMIA) for Ovarian Cancer: Harvesting the Power of Multiple Biomarkers (OVA1)

An In Vitro Diagnostic Multivariate Index Assay (IVDMIA) for Ovarian Cancer: Harvesting the Power of Multiple Biomarkers

Dr. Zhang is the inventor of the OVA1 algorithm, and as such is entitled to royalty payments from the sale of OVA1® through a license agreement between Johns Hopkins University and Vermillion, Inc.

Main Points

• The advantages of an in vitro diagnostic multivariate index assay (IVDMIA) in comparison to a single biomarker assay are based on the premise that the single-valued index, with its aggregated information from complementary biomarkers, will outperform each of its component biomarkers used individually.
• The ability of multivariate models to capture complex patterns in high-dimensional data also means that non-disease-related artifacts that happen to confound the samples used to train the models will also be captured.
• The inclusion of biomarkers in an IVDMIA requires that they are complementary, and that they collectively outperform a single marker with respect to the test’s intended use.
• OVA1® (Vermillion, Inc., Austin, TX) combines results from five tests—CA-125 II, prealbumin, apolipoprotein A-1, β2-microglobulin, and transferrin—into a single-valued index between 0 and 10; a higher value corresponds to a higher risk of malignancy.
• The addition of OVA1 to clinical assessment brings significant improvement in sensitivity. This is, however, at the cost of a reduced specificity. During the construction of the OVA1 multivariate model and the choice of cutoff values, a conscious decision was made to emphasize the need for a high sensitivity. This decision took into consideration the need to mitigate the safety concern of OVA1 with respect to its predefined intended use. Because OVA1 is to be used prior to the decision to refer to a specialist, a high sensitivity minimizes the risk of false-negative results for patients who actually have malignant diseases.