The National Health Service-Galleri multicancer screening trial: explanation and justification of unique and important design issues.

Abstract

Despite there being a plethora of multicancer early detection tests, the National Health Service (NHS)-Galleri (ISRCTN91431511) is the only randomized controlled trial (RCT) of a multicancer liquid biopsy in a screening setting thus far. The NHS-Galleri trial has generated much debate, and it has been criticized in the medical press. Some of these criticisms stem from differing opinions over the choice of primary endpoint, others from poor reporting in statements to journalists from those not directly involved in the trial. Some of the debate is positive and relates to the speed of enrollment and the equity in participation, which have shown what is possible in large population-based RCTs. Here we explain our reasoning for undertaking the trial and designing it the way we did. We focus on the reason to consider multicancer screening and why we felt that the results from nonrandomized clinical studies of GRAIL's Galleri test justified a large RCT. We also consider the slow progress in adopting effective cancer screening historically and in reducing cancer mortality through early detection. There is a need to plan now for future research and implementation depending on the results of the trial. NHS-Galleri is the first double-blind cancer screening RCT. It also, unusually, uses late-stage cancer incidence (rather than cancer mortality) as its primary outcome.