Title: Population Health Screening Benefits and Harms: Evidence Synthesis methods to support policy-making
Funder: Department of Health and Social Care

Abstract: Research question What are the most accurate evidence-synthesis methods (for indirect evidence, use of routine data, and international standardisation) to evaluate screening programmes for national policy-makers? Background Policy-makers and governments make decisions about which screening programmes to implement based on synthesis of research evidence. This synthesis and subsequent decisions could be improved through understanding when indirect evidence is appropriate, integration of routine screening data into the reviews, and fostering international collaboration to reduce research waste and improve review quality. Aims The overall aim is to develop a Centre of Evidence Synthesis for Screening Policy, leading international efforts to optimise evidence synthesis for policy-makers, enabling them to maximise benefits of screening and minimise harms and inequity. Evaluate and delineate circumstances under which indirect evidence chains can accurately augment or replace direct evidence in screening evaluations Describe how routine data (e.g. on ethnicity and socioeconomic status) can be used to bridge evidence gaps and assess generalisability in screening evaluations Develop a list of requirements to adapt an evidence review of screening to be applicable across countries. As an exemplar of using indirect evidence chains incorporating routine data, generalisable across multiple countries, evaluate the benefits and harms of incorporating artificial intelligence in breast cancer screening,A cross-cutting theme across all aims is to evaluate the impact by ethnicity and socioeconomic status, to facilitate a reduction in inequity from screening programmes. Methods Policy-makers guidelines for evidence synthesis, and previous reviews (n=1000), will be systematically extracted from websites of 22 national and 2 international policy-making organisations. Previous evidence syntheses from all disease-specific screening programmes with both direct and indirect evidence will be identified and analysed to ascertain drivers of inconsistency in results between approaches. Factors affecting generalisability of direct and indirect trial evidence to practice will be identified using mixed-effect models of routine cancer data from 28 countries. Simulation studies will explore the impact of drivers/factors identified in this study and the literature on accuracy of conclusions. New methodological guidance for international evidence synthesis will be developed by extracting findings from this research, published primary quantitative research, and other methodological guidance, building on the US Preventive Services Task Force analytic framework for evidence synthesis in screening, (best fit framework approach). International consensus for core standards across 22 screening committees will be developed (Delphi methods), and applied to three reviews for UK, Canadian, and Irish policy-makers. A best-practice exemplar review of incorporating artificial intelligence into the breast cancer screening test will be produced, using routine data from 13 million women to supplement the indirect evidence pathway and incorporating all methodological findings. Anticipated impact and dissemination Changes to methodological guidance for screening evidence reviews in the UK, Canada and Ireland, resulting in more evidence-based decisions about all future screening programmes. An international collaboration for multi-national joint evidence reviews in screening, reducing research waste, improving review quality, and producing reviews for countries who do not currently have access. Self-sustaining Centre of Evidence Synthesis for Screening Policy, to improve quality of UK based primary research.

Lay abstract: Doctors offer health screening programmes to hundreds of millions of people worldwide. Men and women have bowel cancer screening. Pregnant women have screening for abnormalities in the baby. Parents of newborn babies have blood spot screening for rare diseases. Both the programmes and the way they are delivered vary between different countries. Governments use research to decide which screening programmes to offer to people. The research shows the benefits of screening. For example, how many lives it might save. The research also shows the harms of screening. Harms can include people getting incorrect test results or unnecessary treatments. Incorrect test results can cause anxiety when they wrongly suggest people have a disease. Unnecessary treatment can happen quite often in screening when the test detects milder disease that does not need treatment because it would never have caused symptoms. This is harmful because of the effects of unnecessary surgical and drug treatments. This programme of work is about how to bring together research evidence. It was designed together with patient and public contributors. The work will enable governments to understand the different benefits and harms of screening. It will help them to make better decisions about which screening programmes to run. In this study, I aim to solve three problems to improve how we bring research evidence together. Sometimes there isn't one big research study giving us direct evidence about the benefits and harms of screening. When this happens we can combine information from smaller studies to give some indirect evidence. But linking those smaller studies can sometimes introduce bias and mislead policy-makers. We do not currently know when it is safe to link smaller studies without this happening. We need to understand how best to use routinely collected data about people who attend screening programmes (e.g. on ethnicity and socioeconomic status). This will improve our understanding of the benefits and harms of those programmes. It will also improve our ability to decide whether to change them. Policy-makers and scientists from different countries often repeat the same evidence reviews on the same screening topics. Other countries don't have the money available to do their own evidence reviews. We need to work out how to summarise research evidence in a way that is useful across several countries. This will reduce wasted effort, and provide useful reviews for countries who do not do their own reviews.In this programme I will systematically look through national guidance from 16 countries. This will involve over 1000 documents about research evidence for different screening programmes. I will also analyse routine data from 13 million women invited to breast screening in England, and data for cancer screening across 28 countries. I will analyse these and produce guidance on how to bring together the evidence. This will address the three problems described and help inform national governments. I will use our findings to devise formal guidance on methods for the UK, Ireland and Canada. This will widen the use of the research findings for evaluating screening programmes in these countries. I will apply the new approach to provide examples of best practice. This will include three reviews for policy-makers in the UK and Canada. To secure the continued impact of this work after the 5-year funding, I will set up a Centre of Evidence Synthesis for Screening Policy. This Centre will bring together researchers in health screening. It will ensure they use the best research methods for screening interventions. It will reduce research waste and give policy-makers research that is useful.

Research activity codes: 4.4 POPULATION SCREENING;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE