Let MCED trials read out on late-stage incidence, with mortality follow-up mandated
Blood tests that look for many cancers at once take a decade to prove they save lives. Regulators could accept fewer late-stage cancers as the first answer, if trials keep counting deaths afterwards.
NHS-Galleri chose stage III/IV incidence as its primary endpoint; regulators have not said whether that suffices for approval or coverage. Propose a formal surrogate-validation exercise pooling individual data from completed screening RCTs (NLST, NELSON, UKCTOCS, ERSPC, Minnesota, NordICC) to estimate the trial-level correlation between late-stage incidence reduction and cancer-specific mortality reduction, and a conditional-approval pathway with mandated mortality follow-up.
- Most lethal cancers are found late · Screening exists for only a few cancers. Pancreatic, ovarian, liver, oesophageal and most lung cancers are found when cure is unlikely.
- Trial design, endpoints and cost · A phase 3 trial takes years and hundreds of millions of dollars, and often answers a question that has already moved on.
NHS-Galleri is the trial that will decide whether a blood test for many cancers at once should be offered by a health system. Its endpoint is a reduction in late-stage cancer rather than deaths, so even a positive result leaves the mortality question to be settled by longer follow-up.
A drug that shrinks tumours or delays progression on scans has not necessarily been shown to help patients live longer or better. Patients and clinicians should ask what the endpoint was; regulators should insist on timely confirmatory trials; and trialists should validate surrogates before relying on them.