NCHR Written Comment on FDA’s Review of the Galleri Multi-Cancer Early Detection Test

September 8, 2026

Re: Docket No.FDA-2026-N-8004 for “Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments-GRAIL, Inc. Galleri.”

We appreciate the opportunity to comment on GRAIL’s Galleri test. Since written comments are due prior to the upcoming Advisory Panel meeting, we will focus on publicly available evidence of the test’s accuracy, diagnostic burden, and evidence of patient benefit.

The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on health and medical issues. We work to ensure that medical treatments, products, services, and policies are based on strong scientific evidence to protect patients and families.

Approval requires clear evidence regarding what Galleri can and cannot detect

Galleri evidence regarding sensitivity, which measures how often the test detects cancer, and specificity, which measures how often it correctly gives a negative result in people without cancer. Initial PATHFINDER 2 results reported 73.7% sensitivity for 12 prespecified cancers, but only 40.4% across all cancers diagnosed within 12 months. The higher advertised figure would give patients the impression that Galleri detects nearly three-quarters of all cancers. Specificity was 99.6%, but only 61.6% of positive results were followed by a confirmed cancer diagnosis.¹ For patients, this means that Galleri did not detect a cancer signal in nearly 6 in 10 people who were later diagnosed with cancer within 12 months, while nearly 4 in 10 people with a positive result had no cancer confirmed. A major problem with the Galleri test is that even when Galleri detects a cancer signal in someone who has cancer, it may incorrectly specify where that cancer is located. This would direct follow-up testing toward the wrong organ, delaying diagnosis. This level of inaccuracy would be problematic for many patients, who would erroneously believe they do not have cancer when they do, or would follow up an anxiety-producing positive result with numerous expensive and, in some cases, invasive tests. At the same time, the patient would undergo numerous unnecessary scans, biopsies, and other tests for a cancer that they do not have, but not get the tests they need for a cancer that is progressing.

Early-stage detection is obviously important for a test intended to find cancer early. Klein and colleagues reported sensitivity of 51.5% overall, but only 16.8% for stage I and 40.4% for stage II, compared with 77.0% for stage III and 90.1% for stage IV.² This study compared people with known cancer with people without cancer, so these figures should not be assumed to represent performance in routine screening. FDA should require results by cancer type and stage for the version of Galleri under review. Reporting that many detected cancers are early-stage does not tell us how many early-stage cancers the test missed.

A patient who receives a Galleri result showing no cancer signal is likely to feel reassured, and if that result is inaccurate, the patient is likely to fail to quickly seek medical advice for early cancer symptoms when they occur, thus delaying diagnosis and treatment. Conversely, a positive result will cause anxiety, and if followed by a negative diagnostic evaluation, it could leave patients uncertain about whether they have cancer. Our work with thousands of patients over our 27 years of existence is consistent with the American Cancer Society’s concerns that the appropriate follow-up remains uncertain when additional testing finds no cancer, and that false-positive results can cause anxiety and unnecessary procedures, while false-negative results can give false reassurance and delay diagnosis. Many patients would erroneously assume that Galleri is a diagnostic test for cancer that can replace recommended screening or evaluation of new symptoms.³

As you consider whether to recommend FDA approval, it is important to determine whether the evidence supports if Galleri accurately detects cancer at an earlier stage and improves overall survival, or if approval would result in widespread use before benefits are established, thereby resulting in harms that outweigh the benefits. FDA should require comparative evidence that Galleri helps patients live longer or improves their quality of life, and that these benefits outweigh the physical, emotional, and financial burdens of testing and follow-up, particularly for patients with false-positive results, unresolved findings, or cancer diagnosed after a negative test.

Approval requires protecting patients from unnecessary harm

Diagnostic follow-up remains a major limitation of Galleri screening. In PATHFINDER, which used an earlier assay version, 57 of 92 participants with positive results (62%) had no cancer diagnosis after additional testing; however, median diagnostic resolution for these participants took 162 days, with 93% undergoing imaging and 30% undergoing additional diagnostic procedures, a category that included biopsies, endoscopy, and other examinations; one patient underwent surgery.³ In the initial PATHFINDER 2 results, the proportion of positive results without a cancer diagnosis within 12 months was lower, at 83 of 216 (38.4%), and median diagnostic resolution for false positives was shorter, at 75 days.¹ While the newer findings look encouraging, these separate studies cannot establish that the newer assay caused these improvements. Nearly 4 in 10 participants with positive results in PATHFINDER 2 had no cancer confirmed, and diagnostic resolution for false positives still took a median of approximately two and a half months. Patients are very afraid of cancer, and months of additional testing are very stressful for most patients and extremely harmful for some. Adding to that stress is the financial cost to patients of additional testing. Our entire healthcare system will share these costs, with particular costs to Medicaid, Medicare, private insurance companies, and patients who would see higher premiums as a result.

Financial burdens begin with the screening test itself. Galleri’s list price is $949, although discounts and financial assistance may reduce that amount. GRAIL states that Medicare and most health insurance plans currently do not cover the test, but of course FDA approval would result in coverage. Moreover, the price of Galleri does not include the cost of diagnostic testing needed after a positive result, insurance coverage is uncertain. As you consider whether the benefits of Galleri outweigh the risks, please consider the psychological and financial costs of investigating a positive result even when no cancer is ultimately found.

The Dana-Farber series confirmed cancer in 11 of 14 patients referred after positive Galleri results. However, this small study limited to referred patients with positive results cannot determine sensitivity or specificity in the screening population or establish that screening improves survival.⁴ FDA approval needs to be based on evidence about complications, radiation exposure, incidental findings, costs, and how long uncertainty persists. A 2026 JAMA observational study also associated NHS-Galleri trial participation with increased regional diagnostic delays during the first year for suspected head and neck, lung, and upper gastrointestinal cancers.⁶ Although this does not prove that Galleri caused individual delays, it raises concerns that additional screening could increase demand for scans, biopsies, and specialist appointments beyond available capacity. FDA should examine whether expanding Galleri screening could lengthen waiting times for diagnostic care, including for patients with cancer symptoms who have not taken Galleri.

Evidence needed to determine whether patients benefit

PATHFINDER 2 does not provide a randomized comparison of patient outcomes against usual care.^1,7 A systematic review, searched through March 2025, found no completed controlled studies establishing screening benefits and insufficient evidence on accuracy and harms.⁸ However, a randomized clinical trial is listed on clinicaltrials.gov, and data from that study must be determined to see if there are definitive clinical benefits such as overall survival rates, rather than evaluating only biomarkers or other surrogate outcomes such as progression-free survival.

The 2026 NHS-Galleri randomized trial did not meet its primary endpoint of reducing stage III and IV cancers combined across 12 prespecified cancers: 706 cases occurred in the intervention group compared with 688 in controls. The reported 14% reduction in stage IV cancers is encouraging, but is a secondary finding and does not establish that Galleri reduces cancer deaths.⁵ Finding cancer earlier can make survival after diagnosis appear longer simply because the time is counted from an earlier date, even if the patient dies at the same time they would have without screening. Screening can also identify cancers that would never have caused harm, exposing patients to unnecessary treatment.

The FDA should require long-term follow-up of patients with both positive and negative results to determine whether the benefits outweigh the risks. Findings should be analyzed and reported by cancer type, stage, age, race and ethnicity, and other relevant patient characteristics. Based on the current peer-reviewed available evidence, the Committee should not recommend Galleri’s approval for cancer screening at this time until that research is completed and the benefits and risks are clearly evaluated. Given current data Galleri should not be approved because of its limited sensitivity, particularly for early-stage cancers; the burden of false-positive results; and insufficient evidence that screening helps patients live longer or improves quality of life. Any proposed screening indication should require evidence that its benefits outweigh its harms in the intended population. Given its limitations, Galleri should neither supplement nor replace recommended screening for breast, cervical, colorectal, lung, and prostate cancers. Without the additional research specified above, the FDA should not consider approving Galleri because patients and physicians cannot make informed recommendations or decisions based on this screening test.

Respectfully submitted,
National Center for Health Research
Washington, D.C.

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