Long-term outcomes of the Treatment of Advanced Glaucoma Study (TAGS): A multicentre randomised controlled trial comparing primary medical treatment with primary trabeculectomy for people with newly diagnosed advanced glaucoma

RESEARCH QUESTION: What is the relative effectiveness of primary medical treatment compared with primary trabeculectomy (glaucoma surgery) for patients presenting with advanced glaucoma in terms of patient reported health status, visual outcome; and cost effectiveness at 10-years?

BACKGROUND: Glaucoma affects 2% of the population over 40 in UK, it is the second most common cause of sight impairment. An aging population will result in increasing numbers with glaucoma. The biggest risk factor for lifetime blindness is advanced disease at presentation, 25% of patients have advanced disease at presentation. Determining the most effective treatment will reduce risk of vision loss and lifetime blindness

AIMS AND OBJECTIVES: to determine whether primary medical treatment or primary surgery treatment (trabeculectomy) is more effective and cost effective for patients presenting with advanced glaucoma DESIGN: pragmatic randomised controlled trial SETTING: 27 UK hospitals TARGET POPULATION: Adults presenting with advanced glaucoma recruited to TAGS who agreed to long-term follow-up (LTFU)

INCLUSION CRITERIA: Patients enrolled in TAGS who agreed to LTFU EXCLUSION CRITERIA: Patients enrolled in TAGS who withdrew or are unable to complete LTFU

HEALTH TECHNOLOGIES ASSESSED: Primary medical treatment (stepped escalation of medications) or primary surgery (augmented trabeculectomy) PRIMARY OUTCOME: Vision specific Quality of Life (QoL) measured with NEI-VFQ-25

SECONDARY OUTCOME: Clinical effectiveness measured with IOP, VA, VF. Safety of intervention. General Health status measured with EQ5D and HUI-3 and glaucoma related QoL measured with GUI. Cost-effectiveness

SAMPLE SIZE: The sample size is fixed by the original TAGS design. The primary outcome is collected from participants and currently about 79% of the 401 that consented to LTFU are still providing primary outcome data (N=316). At 10-years assuming the same standard deviation of 16 in both groups and assuming the same amount of attrition, we will retain approximately 250 (62%) of LTFU cohort, the anticipated width of the 95% CI will be 7.9.

Extra precision will be gained from using the yearly responses in a repeated measures analysis making use of all follow-up data.

MEASUREMENT OF COSTS AND OUTCOMES: Clinical, patient reported and economic outcome between the two treatments will be determined. All outcomes will be evaluated at 10-years, this is sufficient time to capture long-term differences in effects and accurately profile the different patient pathways associated with each primary intervention.

All 10-years data will be collected at a routine clinic visit. IOP will be measured using two observer technique to minimize bias and VFs will be graded by an independent reading centre. Data from years 5-9 will be collected from notes.

TIMETABLE: Prefunding: protocol development; ethics, HRA and R&D approvals; Months:1-3 Study initiation; assemble team NHS approvals, start site set up; Months 3-27:complete 10-year follow-up visits and upload of data; Months 27-30:close down, analysis, reporting.

ANTICIPATED IMPACT AND DISSEMINATION: NICE guidelines will be updated to reflect outcomes from 10-years. Robust evidence to inform choices of treatment for patients. We will have a knowledge exchange event and publish via the HTA webpage and specialist journals. The results will be presented at professional conferences and directly to patients via patient group meetings and the Glaucoma UK charity.