A Recipe for Proteomics Diagnostic Test Development: The OVA1 Test, from Biomarker Discovery to FDA Clearance

Abstract

Although diagnostic test development remains challenging, novel technologies, including proteomics, genomics, and microRNA analysis, provide opportunities to identify biomarkers that in principle could accelerate the development of new diagnostic tests. Unfortunately, the literature is littered with initial biomarker discoveries that have failed to reach the clinic. We sought to identify a recipe that combines the basic ingredients of clinical research with novel analytical tools to create a new diagnostic test. In the test kitchen, we understood that the most important ingredient is the unmet clinical need. Having made the decision to develop a test for ovarian cancer, we discussed with clinicians what they felt were the most pressing needs in this field. Our initial instinct was to pursue ovarian cancer screening, but in our conversations with key opinion leaders, including Ian Jacobs (University College London), Bob Bast (MD Anderson), and Daniel Chan (Johns Hopkins University), we came to understand that because of the low prevalence of ovarian cancer, development of a screening test would require large studies that would exceed our budget and time constraints. Additionally, because a positive initial result in a screening test would likely lead to pelvic surgery, the test would demand a level of clinical specificity that we were unlikely to achieve. Our colleagues, however, identified a critical unmet need in the area of ovarian tumor triage. Although ovarian tumors are relatively common, only a fraction of them are malignant. Being able to identify the malignant ones preoperatively would permit better preoperative management of women with ovarian tumors. In particular, women with a high likelihood of malignancy could benefit from referral to specialist surgeons (e.g., gynecologic oncologists), who would be able to perform debulking and staging surgeries that form the basis of optimal care for ovarian cancer (1). Having identified the clinical question, we found …