title: Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study).
abstract: BACKGROUND
  The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis.
  
  
  OBJECTIVE
  To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness.
  
  
  METHODS
  This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands.
  
  
  RESULTS
  The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.m.schauwvlieghe@amc.uva.nl.
authors.forename: A M E
authors.initials: AM
authors.lastname: Schauwvlieghe
authors.affiliation: Department of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands. G.Dijkman@lumc.nl.
authors.forename: G
authors.initials: G
authors.lastname: Dijkman
authors.affiliation: Department of Ophthalmology, University Medical Center Groningen, Groningen, The Netherlands. j.m.m.hooymans@ohk.umcg.nl.
authors.forename: J M
authors.initials: JM
authors.lastname: Hooymans
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. f.d.verbraak@amc.uva.nl.|Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. f.d.verbraak@amc.uva.nl.|Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. f.d.verbraak@amc.uva.nl.
authors.forename: F D
authors.initials: FD
authors.lastname: Verbraak
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. C.Hoyng@ohk.umcn.nl.
authors.forename: C B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands. m.g.dijkgraaf@amc.uva.nl.
authors.forename: M G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.affiliation: Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands. r.vanleeuwen@umcutrecht.nl.
authors.forename: R
authors.initials: R
authors.lastname: Van Leeuwen
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. j.vingerling@erasmusmc.nl.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. j.vingerling@erasmusmc.nl.
authors.forename: J R
authors.initials: JR
authors.lastname: Vingerling
authors.affiliation: Department of Ophthalmology, VU University Medical Centre, Amsterdam, The Netherlands. a.moll@vumc.nl.
authors.forename: A C
authors.initials: AC
authors.lastname: Moll
authors.affiliation: Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.schlingemann@amc.uva.nl.|Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.schlingemann@amc.uva.nl.|Netherlands Institute for Neurosciences, Amsterdam, The Netherlands. r.schlingemann@amc.uva.nl.|Medical Retina Unit and Ocular Angiogenesis Group, Department Of Ophthalmology, Academic Medical Center, Room A2-122, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. r.schlingemann@amc.uva.nl.
authors.forename: Reinier O
authors.initials: RO
authors.lastname: Schlingemann
mesh_terms: D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000191:economics*; D000068258:Bevacizumab / Q000191:economics*; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics*; D004311:Double-Blind Method; D016527:Drug Costs; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics*; D008297:Male; D000069579:Ranibizumab / Q000191:economics*; D011795:Surveys and Questionnaires; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab