Screening & monitoring
Multi-cancer early detection blood test (cell-free DNA)
Graded on: incidence of late-stage (III and IV) cancer at diagnosis, a stage-shift surrogate for cancer mortality.
Grade D, tested: a human randomized trial looked for a benefit on the endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. graded and did not find one. How to read a grade →
Compare this record with another, side by side →
How this letter has changedLatest: October 2026 · Corrected.
The grade basis said stage IV alone improved; the rate ratio was 0.86 with a confidence interval The range the true effect probably falls in. A wide interval means the estimate is uncertain. reaching 1.00 (Sasieni et al., NEJM, 2026; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 42776074), a trend, not a demonstrated improvement, and the text now says so. Late-stage incidence is a stage-shift surrogate for cancer mortality, so the endpoint type is corrected from hard to surrogate, with the UK National Screening Committee position statement cited (Batson et al., BMJ, 2026; PMID 42185047). The Mann 2026 spillover analysis (PMID 42217468) now states its result, a transient rise in diagnostic delay the authors judged immaterial, and is labeled observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other.. The AHRQ systematic review A review that searches for every study on a question using a method set in advance, then assesses them together. (Kahwati et al., Ann Intern Med, 2025; PMID 40953446), which found no completed controlled study showing screening benefit, is added. D Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale. unchanged; funding disclosure retained. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 40953446 PMID 42185047 PMID 42217468 PMID 42776074
Funding stated beside the letter. The NHS-Galleri trial, Sasieni 2026 (PMID 42776074) with the test-performance paper Neal 2026 (PMID 42773209), was funded by GRAIL, which sells the test, with GRAIL employees among the authors. The evidence already said so; it now also prints beside the letter.PMID 42776074 PMID 42773209
Every change to a letter on this site is dated and published. The full evidence log →
Multi-cancer early detection tests look for signs of many cancers in a single blood draw. A large study in England tested one of these tests in the people it is sold to. It did not lower the number of cancers found at a late stage, which was its main goal. A test that finds signals is not the same as a test that helps people live longer.
A letter describes the human evidence, not the product, the manufacturer, or the intervention's worth.
See the full evidence record →Funding: The single trial this Grade D rests on was funded by the maker of the device it tested, GRAIL. The funder's role in design and analysis is not stated here, because the full trial report could not be read. The letter is what the trial supports under the grading rules; the funding is stated here so it can be weighed alongside it. Investigators: The single trial this Grade D rests on was run by investigators employed by, founded by, or belonging to the organization that developed, sells or teaches the intervention (GRAIL, which sells the test, with employees among the authors). The funder may read non-commercial; the people who ran the trial are part of the organization whose intervention they tested, which is stated here so it can be weighed alongside the letter.
This was not skipped. A human randomized trial has tested it and did not find a benefit on the endpoint below. That is a different statement from an untested intervention, which may still turn out to work. A Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale. Grade D means nobody has looked. A Route 2 Grade D means somebody looked and the answer was no.
Population NHS-Galleri: 142,250 adults aged 50 to 77 in England, randomized 1:1 to the test plus usual care or usual care alone, up to three annual screening rounds
Certainty High for the primary endpoint. Incidence rate ratio 1.03 (95% CI 0.92 to 1.14, P = 0.63): no reduction. Stage IV alone, a key secondary endpoint An outcome a trial also measures but did not choose as its main test., had a rate ratio of 0.86 (95% CI 0.74 to 1.00), a nonsignificant trend toward fewer stage IV cancers that cannot override the primary result. Trial funded by GRAIL, which sells the test.
PMID 42776074 →
Graded on Incidence of late-stage (III and IV) cancer at diagnosis, a stage-shift surrogate for cancer mortality.
Why this gradeGrade D, tested, no benefit. The reasoning, and what the grade does not cover.
Grade D on Route 2: tested, no benefit demonstrated. This is not an untested technology and the D is not a statement about plausibility. NHS-Galleri was run at scale, randomized, in exactly the population the test is marketed to, and it missed its primary endpoint of reducing late-stage cancer at diagnosis. Stage IV alone showed a nonsignificant trend toward fewer cancers (rate ratio 0.86, 95% CI 0.74 to 1.00), which is the finding proponents cite; a secondary endpoint whose interval reaches 1.00 is not a demonstrated improvement and cannot override the primary. EBL grades against the endpoint the trial itself pre-specified.
THE COMPARISON THAT MATTERSEBL grades fecal immunochemical testing A, because randomized trials show it reduces colorectal cancer mortality. That is what an A-grade screening test looks like. A test detecting a signal is not the same as a test changing an outcome, and the distance between those two claims is this entire grade.
A SPILLOVER SIGNAL WORTH READINGthe JAMA analysis (PMID 42217468) found diagnostic delay rates for suspected head and neck, lung and upper gastrointestinal cancers rose 3.4 and 4.8 percentage points in trial regions during the first year, then no longer differed; the authors judged it unlikely to affect the trial's interpretation. It is observational and carries no grade.
THE ENDPOINT IS A SURROGATElate-stage incidence stands in for cancer mortality, which no multicancer detection trial has reported, and the UK National Screening Committee has said such surrogates cannot yet replace mortality (PMID 42185047). The AHRQ review found no completed controlled study showing screening benefit (PMID 40953446). One randomized trial exists, so nothing here is replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away..
WHAT THIS GRADE DOES NOT COVERthis letter grades the Galleri test used for population screening in asymptomatic adults, judged against the endpoint the trial itself pre-specified. It does not grade the test's analytical performance, which is a separate question about detecting a signal rather than changing an outcome. It does not grade its use in someone with a known cancer or a clinical suspicion of one, which the trial excluded. And a D here is not a claim that no multi-cancer blood test can work. It is a statement about what this one did in the largest trial anyone has run.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
The harm of a screening test is what follows the result. In the trial on this record the test missed its primary endpoint, so a negative result is not evidence that cancer is absent, and a positive one commits the patient to a diagnostic work-up before anything is known. False reassurance and investigation of a finding that proves benign are both outcomes of taking it.
The evidence, in fullSix papers, each linked to its PubMed record.
Sasieni et al. (New England Journal of Medicine, 2026; PMID 42776074): NHS-Galleri primary results, randomized trial of 142,250 adults aged 50 to 77 in England. The incidence of stage III or IV cancer did not differ between groups (rate ratio 1.03, 95% CI 0.92 to 1.14); stage IV alone had a rate ratio of 0.86 (95% CI 0.74 to 1.00). Funded by GRAIL, which sells the test, with GRAIL employees among the authors. Neal et al. (Nature Medicine, 2026; PMID 42773209): prespecified secondary test-performance results from the same trial, descriptive with no hypothesis testing, also GRAIL-funded with company employees among the authors (vendor-authored); positive predictive value 45.8 to 58.0 percent by round and episode sensitivity 26.7 to 37.2 percent for all cancers. Wade et al. (Health Technology Assessment, 2025; PMID 39898371) - NIHR systematic review of blood-based multi-cancer early detection tests for general population screening in adults aged 50 to 79 without clinical suspicion of cancer. Mann et al. (JAMA, 2026; PMID 42217468) - observational difference-in-differences study across all 21 English cancer alliance regions: diagnostic delay rates for suspected head and neck, lung and upper gastrointestinal cancers rose 3.4 and 4.8 percentage points in participating regions during the trial's first two 6-month periods, with no significant difference after that; the authors judged the effect unlikely to have materially affected the trial's findings. Observational, so it carries no grade. Kahwati et al. (Ann Intern Med, 2025; PMID 40953446) - AHRQ systematic review: no completed controlled study reports a benefit of screening with multicancer detection tests; accuracy varies by test and study design. Batson et al. (BMJ, 2026; PMID 42185047) - UK National Screening Committee position statement: late-stage incidence is a surrogate that cannot yet replace mortality as the definitive outcome in cancer screening trials. Grade D, Route 2.
Nothing to track. A negative result does not mean no cancer, and a positive signal starts a diagnostic workup rather than answering anything.
Evidence notes: randomized trial, tested, no benefit
Endpoint graded: Incidence of late-stage (III and IV) cancer at diagnosis, a stage-shift surrogate for cancer mortality (surrogate)
Last reviewed: October 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
Primary evidenceSix papers, each linked to its PubMed record.
Sasieni et al. (New England Journal of Medicine, 2026; PMID 42776074): NHS-Galleri primary results, randomized trial of 142,250 adults aged 50 to 77 in England. The incidence of stage III or IV cancer did not differ between groups (rate ratio 1.03, 95% CI 0.92 to 1.14); stage IV alone had a rate ratio of 0.86 (95% CI 0.74 to 1.00). Funded by GRAIL, which sells the test, with GRAIL employees among the authors. Neal et al. (Nature Medicine, 2026; PMID 42773209): prespecified secondary test-performance results from the same trial, descriptive with no hypothesis testing, also GRAIL-funded with company employees among the authors (vendor-authored); positive predictive value 45.8 to 58.0 percent by round and episode sensitivity 26.7 to 37.2 percent for all cancers. Wade et al. (Health Technology Assessment, 2025; PMID 39898371) - NIHR systematic review of blood-based multi-cancer early detection tests for general population screening in adults aged 50 to 79 without clinical suspicion of cancer. Mann et al. (JAMA, 2026; PMID 42217468) - observational difference-in-differences study across all 21 English cancer alliance regions: diagnostic delay rates for suspected head and neck, lung and upper gastrointestinal cancers rose 3.4 and 4.8 percentage points in participating regions during the trial's first two 6-month periods, with no significant difference after that; the authors judged the effect unlikely to have materially affected the trial's findings. Observational, so it carries no grade. Kahwati et al. (Ann Intern Med, 2025; PMID 40953446) - AHRQ systematic review: no completed controlled study reports a benefit of screening with multicancer detection tests; accuracy varies by test and study design. Batson et al. (BMJ, 2026; PMID 42185047) - UK National Screening Committee position statement: late-stage incidence is a surrogate that cannot yet replace mortality as the definitive outcome in cancer screening trials. Grade D, Route 2.
This page carries a letter. EBL takes no commission, referral fee or payment of any kind on anything it grades. No letter has been bought and none is for sale. Products listed under this modality may be commercial partners, and their purchase links may earn EBL a commission. Those products carry no letter of their own, every relationship is disclosed beside the link, and where a product does not deliver what the trials tested, this page says so regardless of who pays.
How this is enforced
That is not a promise, it is a build condition. Two checks run on every deploy: one refuses to publish if a commission is claimed on anything graded, the other refuses if a page names a commercial relationship that is not declared in the register. If either fails, this page does not go live. You can read how the checks work, and what they do not cover, on the evidence integrity page.
Evidence Based Longevity, Inc. is owner-operated and edited by Arnold Sandlow, D.C., a California-licensed chiropractor. Evidence Based Longevity publishes in English only · Machine translations are not produced or reviewed by EBL for accuracy
© Evidence Based Longevity, Inc.. All rights reserved
These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →