PMA and LDT
In the US, a clinical laboratory test can reach patients through one of two main pathways.
- The first is FDA Premarket Approval (PMA), which is the pathway designed for medical devices (including diagnostic tests). Under PMA, the developer of a device or test must submit extensive analytical and clinical evidence to the FDA before the test can be marketed. The FDA conducts an independent review of safety and effectiveness, which typically includes convening an advisory committee of outside experts and issuing a formal approval decision. The process can take years and cost tens of millions of dollars or more.
- The second is the Laboratory-Developed Test (LDT) pathway, which is the pathway designed for tests designed, manufactured, and performed within a single laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). CLIA certification, administered by the Centers for Medicare & Medicaid Services, ensures the laboratory meets quality standards for personnel, equipment, and proficiency testing. CLIA does not evaluate whether a test works for its intended purpose. The FDA has historically exercised "enforcement discretion" over LDTs, meaning the agency has asserted authority to regulate these tests as medical devices but has chosen not to enforce that authority for most LDTs. The result is that a test sold as an LDT can be offered to patients without the FDA “approving” its effectiveness.
FDA Approval Requirements
For companies pursuing FDA approval, the PMA process is the relevant regulatory process. A PMA submission for a novel diagnostic test typically includes analytical validation (demonstration that the test consistently and accurately measures what it claims to measure), clinical validation (demonstration that the test performs accurately in the intended clinical population), clinical utility evidence (data suggesting the test's results lead to actions that benefit patients), and safety data. The FDA typically convenes a Medical Devices Advisory Committee panel to review a submission. The panel includes external experts who evaluate the data independently of the company and the FDA.
Breakthrough Device Designation is a separate FDA program from PMA approval. The designation is not a finding of safety or effectiveness and is granted (often years before any PMA submission) to devices that treat or diagnose a life-threatening or irreversibly debilitating condition and meet one of four criteria: represent a breakthrough technology, have no approved alternatives, offer significant advantages over existing alternatives, or whose availability is in the best interest of patients. The designation confers enhanced FDA engagement during development (priority pre-submission review, senior-management engagement, "sprint discussions" to resolve specific issues, and an agreed Data Development Plan), and procedural benefits during the eventual PMA review, including the ability to submit a PMA in modules and priority over non-breakthrough applications.
Shield’s Precedent
On July 29, 2024, the FDA approved Guardant Health's Shield blood test for colorectal cancer screening (not their MCED test, Shield MCD), which was the first blood-based cancer screening test ever to receive FDA PMA approval. Skeptics had argued that the sensitivity limitations of blood-based tests would be a regulatory obstacle, but the advisory committee voted 7 to 2 that Shield's benefits outweighed its risks. This signaled the FDA is willing to approve blood-based cancer screening tests with imperfect sensitivity, provided the clinical context supports the risk-benefit calculus. The ECLIPSE study supporting the Shield approval included 20,000 participants in a prospective observational study (it was not an interventional trial nor was it a randomized controlled trial). This suggests the FDA does not necessarily require randomized controlled trial-level evidence for it to grant PMA to a cancer screening test.
An Overview of Where Each Company Stands
To put the framework above in concrete terms: GRAIL completed its modular PMA submission for Galleri (which holds Breakthrough Device Designation) on January 29, 2026, with FDA review underway. Guardant also holds Breakthrough Device Designation for Shield MCD (granted June 2025), but has not filed a PMA. Exact Sciences has neither a designation nor a PMA filing for Cancerguard, and is currently relying on the LDT pathway while running an FDA-reviewed real-world evidence study under an Investigational Device Exemption. Commercial availability, pricing, and study comparisons are covered in Post #10.
The Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act
On February 3, 2026, the Consolidated Appropriations Act was signed into law, and included in the spending package was the Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act. The bill was named after the mother of Representative Terri Sewell of Alabama, who died of pancreatic cancer in 2021.
Previously, Medicare could only cover cancer screening tests that had received a recommendation from the USPSTF, which typically requires high-quality randomized controlled trial evidence and can take years. This Act thus allowed for MCED tests to bypass this process, as MCED tests (as of 2026) do not carry a recommendation from the USPSTF.
Starting January 1, 2029, Medicare beneficiaries aged 50 to 65 are eligible for one MCED test per year. Each subsequent year, the upper age limit increases by one year (so, those aged from 50 to 66 in 2030, those aged from 50 to 67 in 2031, and so on). The test must have FDA approval and must analyze cell-free nucleic acids from blood using genomic sequencing, or be a comparable test determined by the Secretary of Health and Human Services. The law explicitly states that MCED test coverage does not replace or diminish existing coverage for other cancer screening procedures or tests. The Medicare reimbursement rate, through December 31, 2030, is $509. After January 1, 2031, the rate becomes the lesser of either $509 or the rate determined under the Clinical Laboratory Fee Schedule, which seems to mean that the $509 figure is a ceiling.
Current Coverage
As of 2026, Medicare does not currently cover any MCED test, and the earliest possible coverage is 2029. TRICARE, the healthcare program for US uniformed service members, retirees, and their families, covers Galleri for eligible beneficiaries aged 50 and older with elevated cancer risk (one test per lifetime). A handful of Medicare Advantage plans have started to cover MCED testing, such as Priority Health in Michigan. Commercial insurance coverage is sparse, as GRAIL states that a "limited number" of health insurance plans cover the test.
Downstream Cost
One reimbursement question that seemingly gets little attention is regarding who pays for what happens after a positive MCED test result. The diagnostic workup may include PET-CT imaging, diagnostic CT scans, endoscopy, biopsy with pathologist interpretation, and specialist consultations, each costing on the order of hundreds to thousands of dollars. In PATHFINDER 2, diagnostic resolution took a median of 46 days. Some MCED companies have recognized this downstream cost issue explicitly by offering a patient imaging assistance program for individuals who receive a positive test result, aimed at helping to defray the cost of the diagnostic workup.
On a similar note, the allocation of limited resources to the diagnostic evaluation of positive test results is worth noting. Practically speaking, a slot for someone with an (unknowingly) false positive test result for a scan, procedure, or visit with a specialist could theoretically "take away" those slots for a patient who has cancer. This would prolong the time to diagnosis and treatment for some patients with cancer (probably those who seek care in resource-limited settings).
One of the economic arguments for MCED testing stems from the idea that finding and treating cancer at an early stage is cheaper than having to treat a stage IV cancer, as drugs used in this setting can cost hundreds of thousands of dollars (or even millions of dollars) per year. But, the studies in this book have shown that the tests are better at identifying advanced-stage cancers than early-stage ones, and the theoretical calculations of determining the cost that MCED tests are able to save by detecting at least some cancers earlier are challenging.