All Times EDT
Keywords: diagnostic test, sensitivity, specificity, predictive value, lead time bias, stage migration bias
As cancers grow, evolve, and spread, they shed circulating tumor (ct) cells, as well as other tumor-associated cells and products, into the bloodstream. Diagnostic tests are being developed to detect ctDNA in a blood sample for the purpose of screening asymptomatic, average cancer-risk subjects for any cancer. For such pan-cancer tests, a test positive result could be accompanied by a prediction of the primary cancer site (tumor of origin) and would typically lead to referral of the subject to imaging work-up (e.g., PET-CT, MRI) in an effort to locate the putative cancer. Test negative subjects are typically recommended to continue to be screened with available standard of care tests at recommended screening intervals.
In this roundtable, we will discuss study design and statistical evaluation of pan-cancer tests, including: 1. Endpoints for clinical studies of diagnostic accuracy and clinical benefit (also known as clinical utility); 2. Study designs for diagnostic accuracy and clinical benefit, including (i) prospective and retrospective diagnostic accuracy studies, (ii) when a diagnostic accuracy study would not suffice, (iii) study designs for evaluating if a pan-cancer test improves clinical outcome(s) (i.e., provides clinical benefit), and (iv) potential study design biases; 3. Evaluation of the benefit-risk of a pan-cancer test, acknowledging that the consequences of test results are very different for different cancer types. For example, early stage CRC is curable by biopsy during colonoscopy, a false positive for ovarian cancer may lead to unnecessary pelvic mass surgery and resulting morbidity, and a test positive for pancreatic cancer may not provide a net benefit if no safe and effective treatment options are available; 4. Added value of the pan-cancer test over standard-of-care screening tests; and 5. Temporal placement of a pan-cancer test among the armamentarium of available SoC tests