Advances in molecular and genomic technology are creating a maze of new options for payers and patients replete with quite a few meaningful improvements as well as some dead ends.
Public and private payer coverage for diagnostics is shifting, from "relatively low entry barriers to much higher, evidence-based barriers that will require test developers to generate evidence of net clinical benefits before widespread clinical use," observe University of California San Francisco epidemiologist John Peabody, MD, and other researchers in the American Journal of Managed Care.
The paradigm for new diagnostics, argue Peabody and colleagues, is moving from clinical validity, simply proving that a test can confirms or rules out a disease or lesion, to clinical utility -- establishing usefulness and value for patients.
For a long time, commercial and government health insurers have been paying for diagnostics vetted only through the clinical validity model, and these days some tests, particularly invasive ones, are considered to be of limited clinical utility, with risks of complications and false positives.
While the Food and Drug Administration only requires clinical validity in its approval process, clinical utility is a prerequisite for Medicare coverage, and last year the Centers for Medicare & Medicaid Services started using a "gap-filling methodology" to determine lab fee schedule for molecular tests on Medicare claims, in which labs submit cost information on given tests.
CMS contractors can now examine and compare costs from different manufacturers to guide pricing -- offering "new clarity" that "enhances assessment of clinical utility," Peabody argues.
Lessons from public payers
One CMS contractor, Palmetto GBA, has been using a new vetting process for molecular diagnostics since 2011, for a coverage area that includes California, Hawaii and Nevada. Of 34 applications for CMS coverage of molecular diagnostics in the first half of last year, 12 were denied by Palmetto for lack of clinical utility data -- offering some lessons in approaching the new paradigm, Peabody and colleagues found.
Among those denied were a risk stratification test to identify patients at high mortality risk following early-stage lung cancer surgery, a genotype test aimed at predicting cardiovascular disease patients who benefit from aspirin therapy, and a blood test that sought to determine whether patients have a high risk of developing type 2 diabetes within five years.
The one thing these three and others tests had in common was a lack of clinical utility data, according to Peabody and colleagues. In other words, how would they benefit patients?
The lung cancer test, Pervenio's Lung RS, was determined to accurately identify patients at high risk for mortality following surgery for the earliest stage of lung cancer, but "there was a lack of clinical utility data on how treatment decisions (ie, clinical practice) changed with the use of the assay in the practice setting."
The cardiovascular test, Berkeley HeartLab's LPA-Aspirin genotype test, was unable to secure CMS coverage because it could not demonstrate the target population and appeared to be more of a screening tool rather than a diagnostic. Likewise the the diabetes test, which has been discontinued by its manufacturer, Tethys Bioscience.
Among the tests that were approved by Palmetto, though, are lessons in the benefits of emerging diagnostic technologies and ways to properly vet them.
One, from Myriad Genetics subsidiary Crescendo Biosciences, is a biomarker test that shows disease progression in patients with early rheumatoid arthritis, as a way to help patients and clinicians decide which treatments to use. In addition to clinical validity, the company secured CMS reimbursement in large part thanks to submitting a body of evidence comparing the test to current diagnostics, such as the C-reactive protein test.
Another test is Genomic Health's Oncotype DX Colon Cancer Assay, which identifies genes in colon tumors to gauge the likelihood of recurrence following surgical resection. The company demonstrated that the test could identify those who can benefit from post-operative chemotherapy, while others, with lower recurrence risk, can opt for lower chemo doses or none. Even though no randomized controlled utility study was performed, the company secured coverage with data from multiple sites, providers and outcome comparisons, according to Peabody and colleagues.
Oncotype assays can help patients figure out if they should go forward with more toxic chemotherapy, or avoid it. Another approved test can offer a different kind of insight to help patients avoid other kinds of risks and unpleasantness.
Measuring the expression levels of 23 genes linked to the development and response of atherosclerosis, the Corus coronary artery disease test, from CardioDX, can help diagnose or rule out obstructive coronary artery disease -- a condition often investigated with stress testing, electrocardiograms, CT scans, dye-based angiography or catheterizations. The company secured a positive coverage decision thanks to a longitudinal study showing significant, clinically relevant utility changes to primary care and cardiology patient management, Peabody and colleagues concluded.
Many, many more molecular diagnostics are in the pipeline, bringing payers and patients the potential for benefits -- or only marginal utility.
Along with following public payer coverage decisions, commercial insurers have some new tools to track molecular diagnostics and decide whether and how to cover them. This year, the American Medical Association and McKesson, for instance, entered into a licensing relationship to group and index McKesson's Z-Codes for advanced diagnostics with the AMA's molecular pathology codes in the CPT system.