Clinical Referral to the NHS Following Multi-Cancer Early Detection Test Results from the NHS-Galleri Trial

Ian Lowenhoff^1*Saoirse Olivia Dolly²Rebecca Dowinton Smith²Sara Hiom³Liz Holmes³Peter Johnson⁴Laura King³Richard D Neal⁵Thomas Round²Charles Swanton^6,7Lennard Lee⁸Emma Saxon³

• ¹King's College London, London, England, United Kingdom
• ²Guy's and St Thomas' NHS Foundation Trust, London, London, United Kingdom
• ³GRAIL, Inc., Menlo Park, California, United States
• ⁴NHS England, London, England, United Kingdom
• ⁵University of Exeter, Exeter, England, United Kingdom
• ⁶University College London, London, England, United Kingdom
• ⁷The Francis Crick Institute, London, England, United Kingdom
• ⁸University of Oxford, Oxford, England, United Kingdom

The large, randomised, controlled NHS-Galleri trial (NCT05611632) is assessing the clinical utility of a multi-cancer early detection (MCED) test for asymptomatic cancer screening in England. We describe how we enabled the efficient referral of trial participants into existing National Health Service (NHS) urgent suspected cancer pathways for diagnostic investigations. Participants were enrolled across eight of the 21 Cancer Alliance regions in England, served by 56 Hospital Trusts. We used the existing NHS e-Referral Service (e-RS) and a new e-referral form to enable referrals from the trial into any participating Trust, and to standardise information provided with trial participant referrals. Referrals were made by trial nurses directly into secondary care, minimising any additional burden on primary care. At most Trusts, a designated Trust-based referral coordinator triaged referrals and referred participants into the most appropriate local pathway, selected based on the tissue type or organ associated with the cancer signal (cancer signal origin; CSO). At other Trusts, trial nurses referred participants into the appropriate pathway. Guidance mapping predicted CSO(s) to NHS pathways was provided by the trial team to help clinicians understand trial referrals. The trial team and Trust referral coordinators were responsible for central and Trust-level safety netting measures, respectively. To our knowledge, the NHS-Galleri trial has established the first model for the standardised clinical referral of asymptomatic individuals from a trial into NHS standard-of-care cancer pathways. We hope insights from our work could help accelerate screening trial conduct in the UK, and support MCED population screening programme implementation in future.