Title: Monitoring for neovascular AMD Reactivation at Home: the MONARCH study
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Design: diagnostic test accuracy cohort study to estimate the sensitivity and specificity of home monitoring tests to detect active nAMD in patients previously diagnosed with nAMD. Participants will be followed for >=12 months,accruing on average 6 clinic attendances at which home monitoring and reference test results can be compared. Setting: Homes of patients being monitored by HES for nAMD in 5 NHS hospitals (Belfast,Moorfields,Southampton,Liverpool and Great Yarmouth). Target population: Patients being monitored by HES for nAMD, stratified by time since starting treatment (6-17 months; 18-29 months; 30-41 months) to ensure test performance is estimated across this range of duration of nAMD. Eligibility criteria:patients diagnosed with active nAMD (>=6 months earlier) and currently being treated with an anti-VEGF drug or monitored (i.e.with active or inactive nAMD) by the HES will be eligible. Exclusions are: vision in the eye being monitored limited by another eye condition;surgery in the study eye in the previous 6 months; refractive error >-6D; choroidal neovascularization not due to nAMD; inability to do one or more of the proposed tests during ‘training’; unable to understand English; home circumstances cannot support internet access. Health technologies being assessed: 3 home-monitoring tests spanning low to moderate cost and complexity (KSJ, adapted for UK use; MBT app* and mVT app).Participants will carry out these tests weekly. The KSJ is a booklet of near vision tests including a modified Amsler test, with results recorded in the booklet(booklets collected at the next clinic visit). The mVT and MBT apps are display visual stimuli on an iPod Touch, capture participant responses and transmit data by the internet (by home wi-fi or mobile broadband). Reference standard: Classification of eyes being monitored by the HES as active/inactive nAMD based on colour fundus photographs (CF),optical coherence tomography(OCT) fluorescein angiography (FFA) or other investigations carried out as part of usual care at the HES clinic attendance (‘blind’ to home monitoring results). Qualitative study: We will observe test completion and conduct one-to-one interviews during home visits (n=~75 across 3 sites). Carers will be interviewed separately via telephone or e-interview mode (n=~60). Transcripts will be analysed using established qualitative research methods. Sample size: Assumptions: reference standard will be ‘active’ for 30% of monitoring visits; correlations between tests and reference standard will be 0.6 for both active and inactive lesions[1]. We will recruit >=400 participants with test and reference data for about 2300 clinic visits (average 6 visits/participant, 5% attrition). Multiple visits per participant are not independent and measurement error will dilute power to discriminate test performance, so we have assumed an effective sample size of 1200 visits, giving 90% (80%) power to detect a difference of 0.06(0.05) in the area under the receiver operating characteristic curves (AUROC) for 2 tests if the AUROC is 0.75[1]. Projected timetable:Total duration,42 mths: set up sites, mths 1-6; recruit, mths 7-24; follow-up mths 8-36; analyses/draft study report, mths 37-42. Assuming that each centre has >500 patients being actively monitored (at varying times since diagnosis), that 60% will be eligible and >25% of eligible patients will consent, we estimate that sites will each recruit ~80 participants in 18 months.

Lay abstract: Wet age-related macular degeneration (AMD) is the commonest cause of blindness in the UK. It involves new vessels growing and leaking at the back of the eye. Recent treatments for wet AMD have led to a significant reduction in the number of wet AMD patients being registered blind. However, providing prompt access to clinics for regular surveillance and treatment has proved a major challenge for the NHS. Most patients need a series of monthly injections followed by a period of regular check-up visits in case more injections are required. AMD can often flare up after a period when treatment has not been required so check-ups are usually needed for several years. Home monitoring to detect the need for treatment could mean that patients would not need regular hospital check-ups, allowing HES clinic appointments to be kept for patients likely to require treatment. Patients would monitor their vision and request an urgent appointment if home monitoring indicated treatment might be required. This would be more convenient and less costly for both the patient and the NHS. The main aim of our study is to find out whether our chosen home monitoring tests can detect when wet AMD needs to be treated as well as the surveillance tests currently carried out at hospital checkups. We have chosen three home monitoring tests for which some promising results have already been reported. The tests span a range of both technical complexity and cost. The most simple and inexpensive is a paper booklet (KeepSight journal) of self-administered “reading tests” with space for patients to record their results on a weekly basis. Both the second and third tests display shapes or patterns on an iPod touch tablet and patients indicate by entering information on the screen which of four shapes is the odd-man-out or articulate what numbers appear briefly on the screen. Their responses are sent to the research team through the internet. Four hundred existing patients having treatment or check-ups at any of 5 hospitals (Belfast, Moorfields, Southampton, Liverpool, Great Yarmouth) will be invited to take part. They will be asked to perform the tests weekly at home in between standard hospital check-ups over a period of 1 to 2 years. To ensure our results will apply to most patients needing treatment or surveillance, we will recruit patients first diagnosed with wet AMD 6 to 30 months previously. Patients will be trained by an optometrist to perform the tests when they are recruited and will have the opportunity for refresher training throughout the study. A sample of patients and their carers will be interviewed to find out their experiences of performing the tests, focusing on the difficulties experienced and what could be done to make the home tests more acceptable. The team consists of medical experts and researchers who have worked together successfully over 10 years to provide important answers to research questions about the management of wet AMD studies. We are requesting research costs for the applicants, for the research team (study coordination, interviewer, data analyses, IT), the costs of the tests, staff to collect data at participating sites, consumables and travel for the research team. NHS costs cover discussing the study with patients and recruiting participants and training participants in performing the home monitoring tests.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE