Individualised screening for diabetic retinopathy: the ISDR study-rationale, design and methodology for a randomised controlled trial comparing annual and individualised risk-based variable-interval screening

Abstract

Introduction: Currently, all people with diabetes (PWD) aged 12 years and over in the UK are invited for screening for diabetic retinopathy (DR) annually. Resources are not increasing despite a 5% increase in the numbers of PWD nationwide each year. We describe the rationale, design and methodology for a randomised controlled trial (RCT) evaluating the safety, acceptability and cost-effectiveness of personalised variable-interval risk-based screening for DR. This is the first randomised trial of personalised screening for DR and the largest ophthalmic RCT in the UK.

Methods and analysis: PWD attending seven screening clinics in the Liverpool Diabetic Eye Screening Programme were recruited into a single site RCT with a 1:1 allocation to individualised risk-based variable-interval or annual screening intervals. A risk calculation engine developed for the trial estimates the probability that an individual will develop referable disease (screen positive DR) within the next 6, 12 or 24 months using demographic, retinopathy and systemic risk factor data from primary care and screening programme records. Dynamic, secure, real-time data connections have been developed. The primary outcome is attendance for follow-up screening. We will test for equivalence in attendance rates between the two arms. Secondary outcomes are rates and severity of DR, visual outcomes, cost-effectiveness and health-related quality of life. The required sample size was 4460 PWD. Recruitment is complete, and the trial is in follow-up.

Ethics and dissemination: Ethical approval was obtained from National Research Ethics Service Committee North West - Preston, reference 14/NW/0034. Results will be presented at international meetings and published in peer-reviewed journals. This pragmatic RCT will inform screening policy in the UK and elsewhere.

Trial registration number: ISRCTN87561257; Pre-results.

Keywords: diabetic retinopathy; general diabetes; health economics; health policy; medical ophthalmology; medical retina.

Figure 1

Schematic of the ISDR RCT trial design.

Figure 2

Data flows. In step 1, data for consented participants are requested from OptoMize, passed to the DW and cleaned prior to storage. In step 2, data are exchanged between the DW and OptoMize (subjects whose risk needs to be calculated are sent to the DW, subjects for whom their risk and therefore recall interval has been calculated is returned to OptoMize for appointment letter generation). In step 3, the participants’ risk is calculated (when all the covariates are available); if randomisation is required, they are then randomised. The data are then stored in the study database and the DW. All processes in steps 1 and 2 involve identifiable data; the processes in step 3 all use pseudanonomised data for security reasons (the trial team with access to the trial database do not have a need to see raw identifiers). Step 1 occurs on a bimonthly period, steps 2 and 3 occur on a daily basis. Under ideal conditions, it takes 3 days for the data to pass through all parts of steps 1 and 2; this is due to an air gap (manual transfer) at step 2 between the DW and the National Health Service systems. CRF, case report form; DW, data warehouse.