title: Demographics of patients receiving Intravitreal anti-VEGF treatment in real-world practice: healthcare research data versus randomized controlled trials.
abstract: BACKGROUND
  While randomized controlled trials (RCTs) are based on strict inclusion/exclusion criteria, non-interventional studies (NISs) might provide additional information to guide management in patients more representative to the real-world setting. The aim of this study was to compare baseline characteristics of patients receiving intravitreal treatment in the NIS OCEAN with those from published RCTs.
  
  
  METHODS
  The ongoing OCEAN study enrolled patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) or branch/central retinal vein occlusion (B/CRVO). Baseline patient characteristics were compared by indication within the OCEAN cohort. Furthermore, the characteristics were set in reference to those of published RCTs in the same indications. Confidence intervals (CIs) were calculated and assessed for statistically significant differences as indicated by non-overlapping CIs.
  
  
  RESULTS
  Patient characteristics in the NIS OCEAN were evaluated for 3,614 patients with nAMD, 1,211 with DME, 204 with BRVO and 121 with CRVO. Between these groups, significant differences in mean age, gender distributions, and mean baseline VA were seen, reflecting known differences between the indications. Compared to the patient characteristics of published RCTs (trials selected by literature search: nAMD: 13 RCTs, DME: 9, RVO: 5), the OCEAN patients' mean age was significantly higher in every indication. The gender distributions across the trials were comparable, with only few differences between OCEAN and the RCTs. Regarding the mean baseline VA, notable differences were found in nAMD and in DME, with VA significantly higher in some RCTs and lower in others.
  
  
  CONCLUSIONS
  The described differences underline the complementarity of NISs and RCTs. OCEAN covers a broader spectrum and more variability of patients than do RCTs. As baseline values may have impact on the treatment response (ceiling effect), there is an ongoing need for research in all patient subgroups. Country-specific assessments of patient populations can better reflect the real-world situation. NISs can deliver insights that RCTs may not, as NISs can include non-typical patients, patients with comorbidities, a broader age spectrum and patients of various disease stages.
  
  
  BACKGROUND
  The NIS OCEAN was registered on www.clinicaltrials.gov (identifier: NCT02194803 ).
authors.affiliation: Centre for Ophthalmology, Eberhard-Karls-University Tuebingen, Schleichstr. 12, Tuebingen, 72076, Germany. focke.ziemssen@med.uni-tuebingen.de.
authors.forename: F
authors.identifier: http://orcid.org/0000-0002-3873-0581
authors.initials: F
authors.lastname: Ziemssen
authors.affiliation: University Eye Hospital Goettingen, Goettingen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Feltgen
authors.affiliation: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors.forename: F G
authors.initials: FG
authors.lastname: Holz
authors.affiliation: University Eye Hospital, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Guthoff
authors.affiliation: Klinikum Dortmund, University of Muenster, Muenster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ringwald
authors.affiliation: Department of Ophthalmology, and Novartis Pharma GmbH, Georg-August-University Goettingen, Nuremberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bertelmann
authors.affiliation: Novartis Pharma GmbH, Nuremberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wiedon
authors.affiliation: Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Korb
mesh_terms: D017677:Age Distribution; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006302:Health Services Research; D006801:Humans; D015994:Incidence; D058449:Intravitreal Injections; D008269:Macular Edema / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D016032:Randomized Controlled Trials as Topic; D000069579:Ranibizumab / Q000008:administration & dosage*; D012170:Retinal Vein Occlusion / Q000188:drug therapy* / Q000453:epidemiology; D017678:Sex Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab
keywords: Anti-VEGF; Ceiling effect; DME; Demographic characteristics; Epidemiology; NAMD; Non-interventional study; RVO