Multi-cancer early detection tests are emerging as a potentially effective tool that can be used in addition to standard diagnostics. While most health insurers don’t currently cover tests like GRAIL’s Galleri product, more could begin paying for it if the Food and Drug Administration grants it marketing authorization. But given what some experts and clinicians cite as a lack of clear evidentiary benefit, FDA approval doesn’t guarantee reimbursement. Pricing and payment challenges lie ahead for the manufacturers of MCEDs.

As promising technologies , MCEDs could eventually transform the world of cancer diagnosis. They aim to spot signals for different types of cancer from a single blood draw or other body fluid sample, looking for abnormalities that may indicate cancer. Some tests can point to the probable origin of a cancer, while others suggest a cancer may be present without identifying a probable type or location . Besides Galleri, other MCEDs include Exact Sciences’ Cancerguard and Guardant’s Shield.

A key advantage of MCEDs, supporters say, is their potential to identify cancers at earlier, more treatable stages. As such, they could help save lives . This may be particularly useful for cancers with a 0% screening rate today (e.g., pancreatic). Any signal that might lead to an early catch could be beneficial.

GRAIL CEO Josh Ofman presented at the Make America Healthy Again Summit this week, advocating for the use of more predictive healthcare, including MCEDs, such as the company’s Galleri test, which is designed to detect signals associated with more than 50 types of cancer by analyzing patterns in DNA fragments circulating in the bloodstream.

An FDA advisory committee voted in favor of the test last month, implying its potential benefits outweigh its risks. While final FDA approval is pending, the agency usually follows the recommendations of advisory panels.

There is, however, an evidentiary problem that is likely to be important to insurers when they decide on reimbursement. This has to do with failure of Galleri to meet a primary endpoint in a gold standard for evaluating cancer screening programs, namely a randomized controlled clinical trial. A British National Health Service study of the Galleri test was the first of its kind involving an MCED. Though it did result in a 14% reduction specifically in stage 4 diagnoses, Galleri didn’t meet the NHS trial’s primary endpoint: A statistically significant decrease in diagnoses in stages 3 and 4 of cancer.

In the United Kingdom, prior to launching any new national multi-cancer screening program that would be paid for by the single payer NHS, clinical trials of this kind need to show that the use of MCEDs results in fewer cancer deaths owing to earlier diagnoses .

And although MCED tests generally have high specificity or the ability to correctly identify people without cancer, when the diagnostics are applied to a large population where the baseline prevalence of any single rare cancer is quite low, the so-called positive predictive value drops. In the PATHFINDER study associated with the Galleri test, the PPV was around 38%, which implies that almost two-thirds of people who had a detected cancer signal turned out not to have cancer upon extensive diagnostic workup.

Also, some oncologists suggest MCEDs are biased toward catching aggressive, fast-growing cancers that often shed more circulating tumor DNA when they are already advanced, while missing early-stage tumors where screening would actually provide the most curative benefit. Conversely, catching an indolent tumor early could lead to overdiagnosis and possible overtreatment of a cancer that never would have harmed the patient in their lifetime.

Experts I contacted for an Undark piece I published this summer said the Galleri test isn’t yet ready to be deployed as part of population screening. They express concern that routine use by asymptomatic individuals without clear risk factors could lead to unnecessary tests and procedures. False positives can lead to what clinicians call a “diagnostic odyssey,” involving additional blood tests, scans and biopsies to make a proper assessment.

The pathway of follow-on consequences related to such diagnostic odysseys would concern payers, too. Moreover, for insurers, a test’s clinical utility is critical. There is a substantial qualitative difference between a test’s clinical validity (ability to accurately detect what it claims to) and clinical utility (ability to improve patient outcomes by delivering actionable information). Even if validity is shown to be adequate, the value proposition as encompassed by utility is key. Here, payers will want to gauge MCEDs’ value as it relates to the impact on health outcomes for patients.

Most insurers and Medicare don’t cover Galleri at present, which means patients must pay out-of-pocket. The test has a list price of $949.

An article in the Wall Street Journal this week posed the question, will insurers pay ? While it’s largely an unknown at this point in time, a provision in federal government policy does pave the way for potential Medicare consideration starting in 2028 if the test receives final FDA approval. This could be a boon for Galleri.

It’s also noteworthy that GRAIL is sponsoring a 3-year observational study called REACH involving up to 50,000 Medicare beneficiaries. Its goal is to evaluate the real-world safety and clinical effectiveness of adding an annual Galleri test to usual care.

Positive results from REACH could affect coverage not only in Medicare, but also other markets such as the commercial sector and Medicaid.