title: Using Patient-Level Data to Develop Meaningful Cross-Trial Comparisons of Visual Impairment in Individuals with Diabetic Macular Edema.
abstract: The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations.
  
  
  
  A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.5 mg pro re nata or laser photocoagulation monotherapy were predicted, assuming baseline characteristics equivalent to those in the VIVID-DME/VISTA-DME trials. These results were compared with the gain with aflibercept 2.0 mg every 8 weeks in VIVID-DME/VISTA-DME. Sensitivity analyses assessed outcome robustness.
  
  
  
  Baseline BCVA and central retinal thickness differed significantly between trials. In unadjusted data, patients in RESPOND/RESTORE receiving ranibizumab gained an additional 6.6 letters [95% confidence interval (CI): 4.5-8.7] compared with patients receiving laser monotherapy. After adjusting data to assume baseline characteristics equivalent to VIVID-DME/VISTA-DME, patients receiving ranibizumab were predicted to gain an additional 9.9 letters (95% CI: 7.3-12.4) compared with those receiving laser monotherapy. These results were similar (0.1-letter difference in favor of aflibercept; 95% CI: -2.9 to 3.2; P = 0.94) to the gain in BCVA in patients receiving aflibercept in VIVID-DME/VISTA-DME compared with those receiving laser monotherapy (10.0 letters, 95% CI: 8.3-11.7).
  
  
  
  After adjusting for baseline characteristics, the difference in letters gained between patients receiving ranibizumab versus aflibercept was non-significant across trials, highlighting the importance of adjusting for baseline characteristics in future comparisons.
  
  
  
  Novartis Pharma AG.
authors.affiliation: NIHR Biomedical Research Centre, Moorfields Eye Hospital, London, UK.|King's College Hospital, London, UK.
authors.forename: Sobha
authors.initials: S
authors.lastname: Sivaprasad
authors.affiliation: Novartis Pharma AG, Basel, Switzerland. stephane.regnier@novartis.com.
authors.forename: Stephane A
authors.initials: SA
authors.lastname: Regnier
authors.affiliation: Centre Ophthalmologique d'Imagerie et de Laser, Paris, France.|Hôpital Avicenne, Assistance Publique Hôpitaux de Paris, Bobigny, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Fajnkuchen
authors.affiliation: Numerus Ltd, Wokingham, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wright
authors.affiliation: St Michael's Hospital, Toronto, Canada.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Berger
authors.affiliation: University of Sydney, Sydney, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.|National Eye Clinic, Kennedy Center, Glostrup, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D003930:Diabetic Retinopathy / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D053685:Laser Therapy / Q000379:methods*; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D063868:Patient Outcome Assessment; D018579:Patient Selection; D000069579:Ranibizumab / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014786:Vision Disorders / Q000175:diagnosis / Q000209:etiology; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Aflibercept; Diabetic macular edema; Ophthalmology; Ranibizumab; Vascular endothelial growth factor