Title: Using real world data and rapid learning to drive improvements in lung cancer survival
Funder: Department of Health and Social Care

Abstract: Background Radiotherapy plays a major role in curative-intent cancer treatment, but rarely considers the effect of comorbidities on patient outcome. Radiotherapy treatments evolve quickly, typically without formal evaluation of clinical impact. Conventional clinical trials are challenging for rapid and ongoing technical changes, and often under-represent patient groups (e.g. those with co-morbidities). Rapid-learning proposes using real-world data to evaluate such changes in practice and optimise them to the health status of local patient populations in successive learning cycles. This unmet need was highlighted in NHS England s 2019 pledge to develop a Learning Healthcare System for Radiotherapy Services . Recent data suggests limiting heart dose during lung cancer radiotherapy will improve survival. Aims 1. Use rapid-learning to introduce a heart dose-limit for lung cancer radiotherapy and optimise the limit to give the best clinical outcome. 2. Determine the potential and challenges of using rapid-learning across the NHS for the evidence-based introduction and optimisation of changes in radiotherapy treatments. Methods Work-package 1 will determine the ethical, legal and regulatory acceptability of using rapid-learning to change radiotherapy practice. Conceptual analysis will be combined with stakeholder engagement, using citizens juries to reach a consensus position. Work-package 2 will implement the statistical approaches needed to assess clinical impact using real-world radiotherapy data with a rapid-learning methodology. The heart dose-limit data we collect will be used to develop an individualised cardiac dose-limit risk model. Work-package 3 will demonstrate clinical effectiveness of rapid-learning by prospectively optimising heart dose-limits for lung cancer radiotherapy. At least two learning cycles will use real-world data to evaluate the effect of a new dose-limit on patient survival and treatment-related toxicity, and then successively refine the dose-limit. Work-package 4 will generate health-economic evidence of the effect of introducing a heart dose-limit, and evaluate the impact different rapid-learning resource uses will have on this. A patient-level decision-analytic model-based cost-effectiveness analysis will be undertaken using patient reported quality-of-life data from the clinical demonstration. Work-package 5 will investigate if rapid-learning is translatable. Case studies of historic changes in radiotherapy practice will be developed and the statistical approaches adapted for them. Robustness-to-bias analysis will indicate the susceptibility of evidence from different rapid-learning designs to bias in each case. Work-package 6 will investigate the feasibility and barriers to widespread implementation of rapid-learning across NHS radiotherapy departments. Evidence will be synthesised from structured interviews with healthcare professionals, professional societies, regulatory bodies and opinion-formers. Work-package 7 will achieve a consensus position on the role of rapid-learning in the NHS. It will aim to build awareness of rapid-learning in relevant communities and develop pathways to expand the use of the concept beyond the programme. Impact We expect our programme to improve the short-term survival of lung cancer patients (by 15-20%) and establish rapid-learning as a new NHS evaluation framework for technical changes in radiotherapy. We will deliver guidelines and practical tools (software, manuals) to guide the future use of both heart dose-limits and rapid-learning in radiotherapy. An integrated programme of engagement and communication will aim to maximise community involvement and uptake.

Lay abstract: Background to the research Cancer causes more than a quarter of all deaths in the UK. Lung cancer is the leading cause of cancer death with only 1 in 10 patients surviving for 5 years. Radiotherapy is one of the most important cancer therapies curing 4 in 10 cancer survivors. Radiotherapy is often changed to try and improve the chance of patients being cured. For most treatments, researchers use clinical trials to test if changed care improves patients outcomes. However, clinical trials are challenging in the radiotherapy setting and not practical in busy NHS clinics. Clinical trials also tend to under-represent patients from ethnic minorities or those with multiple medical problems. Aims of the research In this study we will use data collected during normal hospital visits to quickly provide evidence about how changing radiotherapy affects the outcomes of all patients. Our vision is to enable the use of routine clinical data across the NHS to improve radiotherapy treatments. We will show this approach is practical and effective by using it to improve the survival of lung cancer patients. Healthcare need Radiotherapy uses radiation beams to destroy cancers. To reach the cancer these beams pass through healthy tissues which can cause harmful side-effects. New research shows that giving radiation to the top of the heart can cause early death when treating lung cancer. We want to change radiotherapy to avoid this area and improve survival. But doing this will put more radiation into other organs in the chest, causing different side-effects. We must balance the risks of different side-effects to give patients their best outcome. Study design We will change how we give radiotherapy to lung cancer patients to limit the heart dose and use routine clinical data to see how their outcomes change. As these data are collected anyway, we will do this without additional cost or patient visits. We can then use the results to refine the dose limit. Repeating this cycle of changing and testing will quickly find the best heart dose limit Stakeholder involvement and value to NHS We will build on this clinical example and work with the NHS, healthcare professionals, patients and the public to find out if this approach is acceptable, safe, good value for money, and can be applied in different cancers. We will find the best way of asking patients to take part in this research to make it as inclusive as possible. We will investigate how routine clinical data should be analysed so that other NHS doctors can trust the results. By investigating how this approach could be used in different hospitals and sharing all our findings, we aim to show how it can become part of routine NHS care.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS