Core outcomes for geographic atrophy trials

Abstract

Background/AimsOngoing and recent clinical trials for geographic atrophy (GA) have used different outcomes. The goal of this study was to identify a core outcome set (COS) important for patients, clinicians and researchers, and to propose the use of COS in the design of future GA trials.MethodsFive-component project including: Delphi method with patients and experts, focus groups and interviews with patients, relatives and workers supporting patients. Three hundred and one patients (301) with age-related macular degeneration participated in round 1 of a Delphi exercise. Most subjects had GA; 183 patients (61%) were females and the median (range) age was 77 (50–99) years. In round 2, of the 301 of the first round, 100 participants were randomly selected of whom 76 agreed to take part. In a parallel Delphi exercise, panellists comprised a mix of non-clinical scientists and clinicians (43 in the initial and 21 in the final round). In addition, interviews and focus groups consisting of patients (n=20), family members (n=4) and support workers (n=5) were undertaken.ResultsCore outcomes identified as important for age-related macular degeneration trials were the health of the outer retina, multimodal estimation of lesion size, reading speed, best corrected distance and near acuity, low luminance visual acuity, patient reported visual performance and safety.ConclusionThis study identified a set of core outcomes that should be used in GA trials. The COS include patient-reported outcome measures, near visual acuity, reading speed and assessment of the outer retina.

Low luminance visual acuity as a clinical measure and clinical trial outcome measure: a scoping review

“…LLD is significantly reduced in patients with macular telangiectasia type 1, choroideremia and pseudoxanthoma elasticum when compared with healthy controls 44,45,50 . LLVA has been recommended as a clinical trial outcome measure for dry AMD, geographic atrophy and retinitis pigmentosa 25,37,75 . In an interventional trial assessing a potential treatment for geographic atrophy, LLVA was significantly reduced in subjects receiving higher doses, thus proving to be a useful safety marker of retinal toxicity 38 .…”

“…44,45,50 LLVA has been recommended as a clinical trial outcome measure for dry AMD, geographic atrophy and retinitis pigmentosa. 25,37,75 In an interventional trial assessing a potential treatment for geographic atrophy, LLVA was significantly reduced in subjects receiving higher doses, thus proving to be a useful safety marker of retinal toxicity. 38 In wet AMD subjects receiving anti-VEGF treatment, LLD showed strong prognostic value, independent of standard VA. A higher proportion of subjects with a small difference between standard VA and LLVA (i.e., small LLD) at screening subsequently experienced significant three-line and sixline standard VA gains compared to those with a larger LLD at screening, who went on to experience larger standard VA declines.…”

“…Efficacy comparisons have been challenging due to the variety of methodologies employed by different study groups ( Table 3 ). Nine investigations did not provide sufficient LLVA methodology details to replicate their study 36,37,42,49,53,58,61,63,65 . Even where detailed test methodology was reported, the luminance levels used appeared to be missing.…”

Core outcome set for three ophthalmic conditions: a healthcare professional and patient consensus on core outcome sets for amblyopia, ocular motility and strabismus (COSAMS Study)

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] To mitigate these issues and to increase the relevance of research, a core outcome set (COS) can be developed, which represents an agreed standardised set of outcomes that should be measured and reported in all studies for a specific area of health or healthcare. A search of the Core Outcome Measures in Effectiveness Trials (COMET) database revealed that there are several studies that have investigated important outcomes for the eyes and vision disease; examples include cataract, 21 22 glaucoma 23 and age-related macular degeneration, 24 but none have specifically looked at amblyopia, strabismus or ocular motility disorders. 25 The aim of this study was to develop COSs for use in clinical trials and routine practice for all intervention types for the treatment of amblyopia, strabismus and ocular motility disorders in children and adults that includes input from all stakeholders.…”

“… 4–20 To mitigate these issues and to increase the relevance of research, a core outcome set (COS) can be developed, which represents an agreed standardised set of outcomes that should be measured and reported in all studies for a specific area of health or healthcare. A search of the Core Outcome Measures in Effectiveness Trials (COMET) database revealed that there are several studies that have investigated important outcomes for the eyes and vision disease; examples include cataract, 21 22 glaucoma 23 and age-related macular degeneration, 24 but none have specifically looked at amblyopia, strabismus or ocular motility disorders. 25…”