Title: Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and economic analysis
Funder: Department of Health and Social Care

Abstract: Diabetic retinopathy is an eye disease occurring in people with diabetes. It causes abnormal blood vessels to grow on the retina at the back of the eye, which can lead to major sight loss over time. The current treatment is to use laser light surgery to prevent the growth of these abnormal blood vessels. Recently a new class of drugs called anti-vascular endothelial growth factor (anti-VEGF) drugs have been successfully used to treat other eye conditions but their value for diabetic retinopathy is less certain; with some concerns over their side effects and whether they are effective in the long-term._x000D_ _x000D_ It is of critical importance that people with diabetic retinopathy, or people who may develop it, have access to the best possible treatments. This will enable them to retain good visual health so that they can continue to work, drive, read, see what is going on around them, and remain independent for as long as possible. This project aims to support this by determining what is best practice for the treatment of diabetic retinopathy, in collaboration with leading clinicians and patient representatives. _x000D_ _x000D_ This project aims to determine whether anti-VEGF therapy is of value, by conducting a thorough review and re-analysis of all the trials where anti-VEGF has been used to treat diabetic retinopathy. As there are several types of anti-VEGF drug, a specialist statistical technique called network meta-analysis will be used, which allows fair and objective comparisons to be made between different drugs. To investigate which types of patient might benefit most from anti-VEGF the original trial data form larger trials will be requested and reanalysed, focussing on analysing the CLARITY trial, conducted in the UK, which compared the anti-VEGF drug aflibercept to laser treatment and included over 200 patients._x000D_ _x000D_ To evaluate whether anti-VEGF therapy is economically viable for the NHS a review of all relevant economic evidence will be performed, and a new economic analysis of anti-VEGF treatment, based on the findings of the project, will be undertaken._x000D_ _x000D_ In collaboration with clinical experts and patient representatives the findings of the project will be considered, and overall decisions made as to whether, and how, anti-VEGF drugs might be used, and whether more trials or investigations are needed before they could be recommended. The findings of the project will be published in an overall report, and in journal articles. Key clinical and patient groups will be made aware of the project and it will be promoted via suitable social media. Plain language and more technical summaries will be made available online to promote understanding of this research.

Lay abstract: Design: _x000D_ Systematic review, individual participant data (IPD) network meta-analysis and economic analysis_x000D_ _x000D_ Aim: _x000D_ To review and compare the effectiveness of all anti-vascular endothelial growth factor (anti-VEGF) drugs for the treatment of diabetic retinopathy, in comparison with laser photocoagulation therapy; also, to investigate whether anti-VEGF drugs are a cost-effective use of NHS resources._x000D_ _x000D_ Background: _x000D_ Diabetic retinopathy is a major form of sight loss in people with diabetes. Older people, men, South Asian groups, and more deprived populations are at higher risk. The most severe form of high risk proliferative retinopathy presents a high risk of severe bleeding, retinal detachment and vision loss. Laser photocoagulation is the primary treatment for proliferative diabetic retinopathy. It is known to be effective and long-lasting but can have side effects._x000D_ Anti-VEGF drugs are used to treat various eye conditions and may be beneficial for the treatment of diabetic retinopathy, but they may have adverse effects. Existing systematic reviews have found some evidence to support the use of anti-VEGF drugs, but most are limited and not up to date. Use of anti-VEGF would substantially increase the costs of treatment, with some concerns that effects may not be long-lasting. _x000D_ _x000D_ Methods: _x000D_ A systematic review of all published and unpublished randomised controlled trials (RCTs) of anti-VEGF and laser photocoagulation for the treatment of diabetic retinopathy will be undertaken. IPD will be sought from all larger trials. A review of non-randomised studies will be performed to identify evidence on outcomes not reported in the RCTs (specifically: long-term vison and adverse effects)._x000D_ All included studies will be pooled in meta-analyses. IPD will be used to identify key patient characteristics that may alter the effectiveness of anti-VEGF therapy. Network meta-analysis will be used to compare different treatments. Threshold analysis will be used to identify areas where existing evidence may not be robust._x000D_ A systematic review of cost-effectiveness studies will be performed to identify and critique previous economic models. A new decision-analytic model will be developed to assess the cost-effectiveness of anti-VEGF therapy. This will assess the cost per quality-adjusted life year (QALY) of included interventions. A Value of Information analysis will be performed to quantify the value of undertaking further research to resolve uncertainties in the existing evidence. _x000D_ _x000D_ Dissemination: _x000D_ A final report for the NIHR HTA Programme will be produced, along with the submission of manuscripts for peer-reviewed publication and conference presentations. The CRD website and social media will also be used to disseminate findings. In collaboration with patient representatives and clinicians, brief evidence summaries, plain language summaries and infographics will be produced to disseminate findings in a comprehensible way to the wider public. These will be disseminated online through the participation of major patient representative groups, including Diabetes UK.

Research activity codes: 6.1 PHARMACEUTICALS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: EYE;METABOLIC AND ENDOCRINE