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.

Background: The United Kingdom has poorer cancer outcomes than many other countries due partly to delays in diagnosing symptomatic cancer, leading to more advanced stage at diagnosis. Delays can occur at the level of patients, primary care, systems and secondary care. There is considerable potential for interventions to minimise delays and lead to earlier-stage diagnosis. Methods: Scoping review of the published studies, with a focus on methodological issues. Results: Trial data in this area are lacking and observational studies often show no association or negative ones. This review offers methodological explanations for these counter-intuitive findings. Conclusion: While diagnostic delays do matter, their importance is uncertain and must be determined through more sophisticated methods.

Background: Missed appointments are a common occurrence in primary care in the UK, yet little is known about the reasons for them, or the consequences of missing an appointment. This paper aims to determine the reasons for missed appointments and whether patients who miss an appointment subsequently consult their general practitioner (GP). Secondary aims are to compare psychological morbidity, and the previous appointments with GPs between subjects and a comparison group. Methods: Postal questionnaire survey and prospective medical notes review of adult patients missing an appointment and the comparison group who attended appointments over a three week period in seven general practices in West Yorkshire. Results: Of the 386 who missed appointments 122 (32%) responded. Of the 386 in the comparison group 223 (58%) responded, resulting in 23 case-control matched pairs with complete data collection. Over 40% of individuals who missed an appointment and participated said that they forgot the appointment and a quarter said that they tried very hard to cancel the appointment or that it was at an inconvenient time. A fifth reported family commitments or being too ill to attend. Over 90% of the patients who missed an appointment subsequently consulted within three months and of these nearly 60% consulted for the stated problem that was going to be presented in the missed consultation. The odds of missing an appointment decreased with increasing age and were greater among those who had missed at least one appointment in the previous 12 months. However, estimates for comparisons between those who missed appointments and the comparison group were imprecise due to the low response rate. Conclusion: Patients who miss appointments tend to cite practice factors and their own forgetfulness as the main reasons for doing so, and most attend within three months of a missed appointment. This study highlights a number of implications for future research. More work needs to be done to engage people who miss appointments into research in a meaningful way.

Background: Tools based on diagnostic prediction models are available to help general practitioners diagnose cancer. It is unclear whether or not tools expedite diagnosis or affect patient quality of life and/or survival.Objectives: The objectives were to evaluate the evidence on the validation, clinical effectiveness, cost-effectiveness, and availability and use of cancer diagnostic tools in primary care.Methods: Two systematic reviews were conducted to examine the clinical effectiveness (review 1) and the development, validation and accuracy (review 2) of diagnostic prediction models for aiding general practitioners in cancer diagnosis. Bibliographic searches were conducted on MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Library and Web of Science) in May 2017, with updated searches conducted in November 2018. A decision-analytic model explored the tools’ clinical effectiveness and cost-effectiveness in colorectal cancer. The model compared patient outcomes and costs between strategies that included the use of the tools and those that did not, using the NHS perspective. We surveyed 4600 general practitioners in randomly selected UK practices to determine the proportions of general practices and general practitioners with access to, and using, cancer decision support tools. Association between access to these tools and practice-level cancer diagnostic indicators was explored.Results: Systematic review 1 – five studies, of different design and quality, reporting on three diagnostic tools, were included. We found no evidence that using the tools was associated with better outcomes. Systematic review 2 – 43 studies were included, reporting on prediction models, in various stages of development, for 14 cancer sites (including multiple cancers). Most studies relate to QCancer^®(ClinRisk Ltd, Leeds, UK) and risk assessment tools.Decision model: In the absence of studies reporting their clinical outcomes, QCancer and risk assessment tools were evaluated against faecal immunochemical testing. A linked data approach was used, which translates diagnostic accuracy into time to diagnosis and treatment, and stage at diagnosis. Given the current lack of evidence, the model showed that the cost-effectiveness of diagnostic tools in colorectal cancer relies on demonstrating patient survival benefits. Sensitivity of faecal immunochemical testing and specificity of QCancer and risk assessment tools in a low-risk population were the key uncertain parameters.Survey: Practitioner- and practice-level response rates were 10.3% (476/4600) and 23.3% (227/975), respectively. Cancer decision support tools were available in 83 out of 227 practices (36.6%, 95% confidence interval 30.3% to 43.1%), and were likely to be used in 38 out of 227 practices (16.7%, 95% confidence interval 12.1% to 22.2%). The mean 2-week-wait referral rate did not differ between practices that do and practices that do not have access to QCancer or risk assessment tools (mean difference of 1.8 referrals per 100,000 referrals, 95% confidence interval –6.7 to 10.3 referrals per 100,000 referrals).Limitations: There is little good-quality evidence on the clinical effectiveness and cost-effectiveness of diagnostic tools. Many diagnostic prediction models are limited by a lack of external validation. There are limited data on current UK practice and clinical outcomes of diagnostic strategies, and there is no evidence on the quality-of-life outcomes of diagnostic results. The survey was limited by low response rates.Conclusion: The evidence base on the tools is limited. Research on how general practitioners interact with the tools may help to identify barriers to implementation and uptake, and the potential for clinical effectiveness.Future work: Continued model validation is recommended, especially for risk assessment tools. Assessment of the tools’ impact on time to diagnosis and treatment, stage at diagnosis, and health outcomes is also recommended, as is further work to understand how tools are used in general practitioner consultations.Study registration: This study is registered as PROSPERO CRD42017068373 and CRD42017068375.Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full inHealth Technology Assessment; Vol. 24, No. 66. See the NIHR Journals Library website for further project information.

Relatively little is understood concerning the exact role of general practice in the cancer patients' pre-diagnostic, and post-diagnostic journey. This paper aims to explore this role using data from the National Survey of NHS Patients-Cancer. Data from 65,192 patients relating to five questions from this survey were analysed in detail with particular relevance to differences between the six cancers [breast, colorectal, lung, ovarian, prostate and non-Hodgkin's lymphoma (NHL)], and socio-demographic variables (age, gender and social class). There were considerable differences between patients with the six cancers, and the role of general practice in the cancer diagnosis, and post-diagnosis management. The vast majority of patients saw their general practitioner (GP) with symptoms prior to being seen in hospital. A significant minority were told their diagnosis by their GP. About half the sample were told to contact their GP post-discharge, and about half did so. Being told to contact the GP post-discharge was strongly associated with actually seeing the GP. Most patients felt that their GP was given enough information about their treatment or condition. In conclusion, this work has quantified the central role of general practice in cancer diagnosis and management in England. There remain considerable resource, educational and research needs to continue to provide high-quality cancer care in primary care.