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.

Trial registration: The NIS OCEAN was registered on www.clinicaltrials.gov (identifier: NCT02194803 ).

Keywords: Anti-VEGF; Ceiling effect; DME; Demographic characteristics; Epidemiology; NAMD; Non-interventional study; RVO.

Fig. 1

Start dates of randomized controlled trials by indication. Legend: RCT start dates shown in relation to EMA and FDA ophthalmological marketing authorisation dates for Eylea®, Lucentis® and Macugen®. For sources of details and study periods for the RCTs see Additional file 2: Table S2. Abbreviations: BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; DME: diabetic macular oedema; EMA: European Medicines Agency; FDA: US Food and Drug Administration; nAMD: neovascular age-related macular degeneration; RCT: randomized controlled trial; RVO: retinal vein occlusion

Fig. 2

Baseline age distribution in OCEAN and patient age for OCEAN and RCTs, by indication. Legend: Age distribution in years by age group for OCEAN and mean age in years (with SD) for OCEAN and RCTs. Mean age is given overall per study (black square) and as mean with SD for each individual treatment group (grey circles with error bars). If the mean was not available, the median is shown (grey squares) with 25^th/75^th percentiles. The data for the individual treatment groups of each RCT are shown in the same order from top to bottom as the treatment groups are presented in Tables 2, 3, 4. ^ano SD available ^bData provided as median (25^th, 75^th percentile). ^cData provided for number of eyes, not number of patients. Abbreviations: BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; DME: diabetic macular oedema; nAMD: neovascular age-related macular degeneration; RCT: randomized controlled trial; SD: standard deviation

Fig. 3

Gender distribution in OCEAN study and in selected RCTs, by indication. Legend: Proportion of female patients (red) and male patients (blue) at baseline. ^aHatched columns: Gender group not explicitly provided in source data; data for respective other gender used for calculation of percentage (may include missing/unavailable data). ^bData provided for number of eyes, not number of patients. Abbreviations: BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; DME: diabetic macular oedema; N: number of patients; nAMD: neovascular age-related macular degeneration; RCT: randomized controlled trial

Fig. 4

Baseline visual acuity distribution in OCEAN and visual acuity for OCEAN and RCTs, by indication. Legend: Visual acuity distribution in ETDRS letter analogues by group for OCEAN and mean visual acuity (in ETDRS letter analogues with SD) for OCEAN and RCTs. Mean visual acuity is given overall per study (black square) and as mean with SD for each individual treatment group (grey circles with error bars). If the mean was not available, the median is shown (grey square) with 25^th/75^th percentiles. The data for the individual treatment groups of each RCT are shown in the same order from top to bottom as the treatment groups are presented in Tables 2, 3, 4. ^aThe visual acuity results for SAILOR are provided for four treatment groups. ^bData provided as median (25^th, 75^th percentile). ^c Data provided for number of eyes, not number of patients. Abbreviations: BRVO: branch retinal vein occlusion; CRVO: central retinal vein occlusion; DME: diabetic macular oedema; ETDRS: Early Treatment Diabetic Retinopathy Study; nAMD: neovascular age-related macular degeneration; RCT: randomized controlled trial; SD: standard deviation