Title: Introducing personalised risk based intervals in screening for diabetic retinopathy: development, implementation and assessment of safety, cost-effectiveness and patient experience.
Funder: Department of Health and Social Care

Abstract: This five year research programme aims to develop a major enhancement to the existing screening process for sight threatening diabetic retinopathy (DR, STDR) for implementation in the NHS. Important evidence gaps in screening for DR will be tackled comprising collection of prospective patient centred data in a whole population cohort study and new knowledge produced on outcomes relevant to patients such as visual impairment (VI). An individual risk-based approach will be developed and evaluated based on evidence collected from a well established diabetes eye care pathway in Liverpool. Safety, cost-effectiveness and acceptability to patients and staff will be assessed. Our mixed quantitative and qualitative approach has been piloted in a NIHR funded programme development grant (PDG) (report available at Appendix 2) and barriers to success identified and overcome. Inter-linked workstreams (WS) will run in parallel, each informing the progress of others. Systematic review In year 1 a systematic review of evidence of variable compared with annual screening intervals will be undertaken using standard methodology. We will estimate from published data sets the rates of visual impairment (VI) and treatment. This information will inform current national screening policies and our related workstreams. Establishment of a study data warehouse In a continuation of our PDG work, demographic, systemic and ocular data will be collected retrospectively and prospectively from primary care and hospital eye service (HES) systems on people with diabetes in Liverpool, linked electronically for individual patients using NHS number. For the first time, data from those already screened positive and attending the HES will be added (retinopathy grading, visual acuity, appointment, treatment) allowing comprehensive analyses. The data warehouse will provide the routinely collected demographic and clinical data needed for the prospective observational analysis, risk engine development, economic modelling, case detection and randomised controlled trial (RCT). Prospective observational study We will use standard statistical techniques to describe the population-based frequency of development of STDR and VI, and the progression to treatment, and to model risk factors for each outcome. The effect of change in screening interval will be simulated for likelihood of progression to first laser treatment and VI. This information will inform a health economics WS and will be used to cross-validate a risk engine. Risk calculation development and testing Known risk factors will be used to develop a risk engine for progression to STDR. A generalised model using a time-varying Cox model will be used. Towards the end of year one the tool will be used to set screening intervals for a RCT based on structured assessment of risk levels and their acceptability to PPI and health professional teams. Data will be added throughout the programme to add further robustness to the model. The risk engine will be extended in later years to model risk of progression from STDR to need for treatment for use in the HES. RCT standard and test screening interval protocols During years 2 to 5 we will evaluate usual care (annual photographic screening) versus individualised variable interval screening (intervals assigned by risk engine) in people with diabetes (PWD) registered with participating Liverpool GPs and eligible for photographic screening. The primary outcome will be non-attendance rate. Secondary outcomes will include STDR detection rate, retinopathy level, false positives, cost of screening and treatment, visual acuity, VI due to DR, missed appointments, patient acceptability measures and health related quality of life (EQ-5D). Health economics modelling An economic model will be constructed for usual care versus variable interval screening. The model will be populated with data from other work streams, such as the risk engine, in addition to specifically collected EQ-5D data and an economic resource use proforma. Sensitivity analyses will be performed around different assumptions on key variables including local population data. An incremental cost-effectiveness ratio will be calculated. Exploring perceptions of screening and variable screening intervals amongst PWD and health care staff In year 1 relevant staff will be invited to focus groups to explore barriers within current practice to variable interval screening and patients will be invited to semi-structured interviews to discuss their opinion about diabetes, concepts of risk, self-care, treatment and screening. Further cycles will explore perceptions of the variable interval approach, identify potential improvements to patient experience and explore applicability to PWD attending the HES (year 4-5). We will also conduct semi-structured interviews with people who never or rarely attend screening to explore and understand possible reasons for their non-attendance. This will be supported by an analysis of demographic and systemic data to identify common characteristics of non-attenders compared with regular attenders. Outputs We will deliver a tested individualised screening system based on contemporaneous pragmatic risk data ready for implementation in the NHS providing new whole population data on progression to patient centred outcomes as well as patient perceptions of risk. Results will be applicable to other research questions and services.

Lay abstract: Diabetic retinopathy (DR) is the commonest cause of visual loss in adults. Screening for DR aims to detect sight-threatening disease (STDR) and refer people with diabetes (PWD) into the hospital eye service (HES) for appropriate treatment. STDR is a definition with limited relevance to PWD. In England the screening interval has been set at 12 months for all PWD; follow up intervals in the HES are variable. Evidence to support the delivery of the pathway is limited to screening research cohorts and with minimal input from users. There are large potential cost savings to the NHS by varying the screen interval but no cost-effectiveness research data other than from limited modelling. The safety and acceptability of extending the screen interval in low risk groups has not been investigated. We will conduct a mixed qualitative and quantitative programme of research aiming to strengthen the evidence base for screening for DR in the UK and beyond. Our approach integrates PWD and professionals at key review points within the programme and introduces care focussed on the individual. Our research team has extensive experience in research in the field and the support of key stakeholders in the UK; it includes academics, service leads and users from all relevant disciplines. We will conduct work streams which will inform each other and develop during the programme. In a development year we overcame important obstacles to improve our chances of success. A whole population cohort (n=18,000) including those within the HES will be recruited and followed to measure risk of progression to patient centred endpoints of treatment and visual impairment. A data warehouse will receive all relevant data from PWD streamed from primary and secondary care. A personalised method of calculating screen interval using a risk calculation engine fed from the warehouse will be developed and evaluated in a randomised controlled trial (RCT) of over 5000 patients. Comparison will be between our risk-based variable interval screening and usual care. Risk factors tested will be demographic (eg. age, deprivation, ethnicity), ocular (eg. previous and current retinopathy severity, previous treatment, vision) and systemic (eg. diabetes control and duration, blood pressure, lipids). Qualitative research methods will be used to assess patient and professional experience and acceptability of risk to underpin interval selection. Direct data collection on costs will allow new health economics insights to be developed and a cost-effectiveness analysis of the RCT. We will deliver new knowledge on patient-centred risks associated with DR and a validated individualised risk-based screening model ready for implementation in the NHS within 3 years of the end of the programme. Our findings will include data on cost-effectiveness, patient safety and acceptability, including of risk of missed disease, to underpin interval setting.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: EYE;METABOLIC AND ENDOCRINE