Psychological Impact of the Galleri Test (sIG(n)al): Protocol for a longitudinal evaluation of the psychological impact of receiving a cancer signal in the NHS-Galleri Trial

Introduction Multi-cancer early detection (MCED) blood tests look for cancer signals in cell-free deoxyribonucleic acid (cfDNA). These tests have the potential to detect cancers at an earlier (asymptomatic) stage, improving cancer outcomes. Any screening method needs careful consideration of the psychological harms prior to implementation. The aim of this research is to explore the psychological impact of having a cancer signal detected following an MCED blood test. Methods and Analysis The project is embedded in the NHS-Galleri trial ([ISRCTN91431511][1]; [NCT05611632][2]), a large clinical trial that has randomised over 140,000 members of the general population aged 50-77 1:1 to either the intervention (blood tested with MCED test) or control (blood stored) arm. This work focuses on participants in the intervention arm of the trial who have a cancer signal detected. All participants who have a cancer signal detected (expected to be around 700 assuming a 1% test positive rate) will be sent a questionnaire at three time points: soon after receiving their result, 6-months and approximately 12-months later. The primary outcome is anxiety, assessed using the short-form State Trait Anxiety Inventory (STAI-6). We will also assess the psychological consequences of screening (using the Psychological Consequences of Screening Questionnaire), reassurance and concern about the test result, as well as understanding of results, cancer risk perceptions and help- and health-seeking behaviour. A sub-sample of 40 participants (20 with a cancer diagnosis and 20 for whom no cancer was found) will be invited to take part in a one-to-one semi-structured interview to explore their experience in depth. Ethics and Dissemination Ethical approval for this work has been granted by the Wales Research Ethics Committee as part of the NHS-Galleri trial (Ref 21/WA/0141). Results will be disseminated via peer-reviewed publication and presentations at national and international conferences. Strengths and limitations ### Competing Interest Statement GRAIL LLC funds full salaries of L.Marlow and N.Schmeising-Barnes as well as 20% of J.Waller salary via a contract with Kings College London (KCL). J.Warwick is also supported by project funding from GRAIL LLC through a KCL contract. This funding also covers article processing charges. ### Clinical Trial ISRCTN91431511; [NCT05611632][2] ### Funding Statement GRAIL, LLC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this work has been granted by the Wales Research Ethics Committee as part of the NHS-Galleri trial ethics application (Ref 21/WA/0141). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes N/A - the article reports a protocol. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN91431511 [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05611632&atom=%2Fmedrxiv%2Fearly%2F2023%2F06%2F12%2F2023.06.12.23291276.atom