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Koenraad Blot,1 Luc Duchateau,2 Benedicte Lescrauwaet,3 Nilani Liyanage,4 David Ray,5 Beloo Mirakhur,5 Aaron I Vinik6 1Alacrita Consulting Ltd, London, UK; 2Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium; 3Xintera Bvba, Ghent, Belgium; 4Ipsen Pharma France, Paris, France; 5Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 6Eastern Virginia Medical School, Norfolk, VA, USACorrespondence: Koenraad BlotAlacrita Consulting Ltd, 2 Royal College Street, London NW1 0NH, UKTel +32 472 846 377Email kblot@alacritaconsulting.comPurpose: The purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT.Methods: The post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis.Results: The three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06).Conclusion: The higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide.Trial registration: ClinicalTrials.gov identifier: NCT00774930.Keywords: lanreotide, patient-reported outcomes, neuroendocrine tumors, NETs

Benedicte Lescrauwaet,1 Koenraad Blot,2 Timothy L Jackson3 1Xintera, Outcomes Research, Ghent, Belgium; 2Xintera, Ghent, Belgium; 3Life Sciences and Medicine, King’s College London, Department of Ophthalmology, King’s College Hospital, London, UK Purpose: Vitreomacular traction (VMT) is a disease in which the vitreous exerts abnormally strong traction on the macula, the area of the eye responsible for detailed central vision. If this traction significantly distorts the macula then VMT can lead to troublesome distorted vision (metamorphopsia), sometimes occurring despite relatively preserved visual acuity. Ocriplasmin, administered as a single intravitreal injection, aims to release VMT and improve vision. While the effect of ocriplasmin on traction release and visual acuity is well characterized, the effect of symptoms like metamorphopsia is not.Methods: A systematic review and synthesis of the literature on patient reported outcomes (PRO) in relation to the use of ocriplasmin for the treatment of VMT was undertaken using MEDLINE and Embase databases, and the Cochrane central register of controlled trials (CENTRAL).Results: The review identified PRO data from 870 patients across three randomized controlled trials. The most commonly reported PROs were the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25), a broad measure of vision-related quality of life, and Visual Function Response (VFR), an outcome combining quality of life and visual acuity outcomes. Treatment with ocriplasmin produced significant patient benefit vs control (sham or placebo-injection). Ocriplasmin was associated with a higher proportion of patients experiencing a clinically meaningful improvement in visual functioning with a difference of 11.8% for VFQ-25 and 23.2% for VFR responder analyses, respectively.Conclusion: Patients with VMT have material impairment in visual functioning and quality of life, relative to their reduction in visual acuity. Ocriplasmin results in a significant improvement in visual functioning. Future research could include the development of new PROs specific to VMT. Keywords: macular hole, metamorphopsia, patient reported outcomes, symptomatic vitreomacular adhesion, vitreomacular traction, visual function questionnaire