Cell-Free DNA–Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial

SIMPLE SUMMARY: NHS-Galleri is a randomised controlled trial that will assess how well a blood test can reduce the number of late-stage cancers by helping to find cancers early. The test looks at patterns in blood samples to detect a cancer signal. NHS-Galleri has enrolled over 140,000 people, invited from the general population of England aged 50–77 years who did not have or were not being investigated for cancer. Blood is being collected up to three times: first when people join the study and again 12 and 24 months later. Half the participants (chosen at random) will have their blood tested and half will have their blood stored. Participants will not be told whether their blood will be tested or stored. Participants with a cancer signal detected result will be sent for further diagnostic testing in the NHS. The trial will help the NHS decide whether to introduce screening using this test. ABSTRACT: We report the design of the NHS-Galleri trial (ISRCTN91431511), aiming to establish whether a multi-cancer early detection (MCED) test that screens asymptomatic individuals for cancer can reduce late-stage cancer incidence. This randomised controlled trial has invited approximately 1.5 million persons and enrolled over 140,000 from the general population of England (50–77 years; ≥3 years without cancer diagnosis or treatment; not undergoing investigation for suspected cancer). Blood is being collected at up to three annual visits. Following baseline blood collection, participants are randomised 1:1 to the intervention (blood tested by MCED test) or control (blood stored) arm. Only participants in the intervention arm with a cancer signal detected have results returned and are referred for urgent investigations and potential treatment. Remaining participants in both arms stay blinded and return for their next visit. Participants are encouraged to continue other NHS cancer screening programmes and seek help for new or unusual symptoms. The primary objective is to demonstrate a statistically significant reduction in the incidence rate of stage III and IV cancers diagnosed in the intervention versus control arm 3–4 years after randomisation. NHS-Galleri will help determine the clinical utility of population screening with an MCED test.