Study Finds Population Differences Between Randomized Controlled Trials, Real-World Studies of Ranibizumab

Ellen Kurek

DME patients in non-interventional studies notably older than in RCTs.

Randomized controlled trials, or RCTs, have strict inclusion and exclusion criteria that can limit the applicability of their findings in routine clinical practice. In contrast, non-interventional studies often include non-typical patients, those with comorbidities, or atypically old or young patients. In addition, the study group in non-interventional studies may comprise a greater range of disease stages.

Thus, non-interventional studies can obtain more generalizable data on the effectiveness of treatments than RCTs can. Moreover, non-interventional studies can provide a more accurate picture of the long-term safety and tolerability of treatments in the real world.

Because most diseases treated with anti-vascular endothelial growth factor (anti-VEGF) agents are age-dependent and often accompanied by substantial comorbidities, age and comorbidity status can be particularly influential in studies of these agents. And because the life expectancy of women is greater than that of men, these retinal diseases are more likely to develop in women, so sex as well as age affects their occurrence and management.

In addition, baseline values may affect treatment responses. Researchers refer to this influence as the ceiling effect: The better a patient’s visual acuity when treatment begins, the more improvement can be expected. The potential impact of the ceiling effect indicates the need for research in all patient subgroups.

The prospective, non-interventional, open-label OCEAN study of the anti-VEGF agent ranibizumab (Lucentis/Roche) is the largest German observational study pursued in ophthalmology so far. OCEAN stands for Observation of treatment patterns with LuCEntis and real-life ophthalmic monitoring, including optional optical coherence tomography (OCT), in Approved iNdications.

Because OCEAN is a non-interventional study, it includes a broader spectrum of patients and has more variability of patients than RCTs do. Therefore, OCEAN may provide valuable data on how to manage patients who are more representative of those in the real world than RCT patients are.

The OCEAN investigators recently compared the baseline characteristics by indication of the 5,606 patients enrolled in their study with those of patients in published RCTs to determine how these baseline characteristics differ. Treatment indications in OCEAN were neovascular age-related macular degeneration (nAMD) in 3,614 patients, diabetic macular edema (DME) in 1,211, and retinal vein occlusion (RVO) in 741.

The OCEAN investigators then calculated confidence intervals (CIs) for the presence of the baseline characteristics and assessed statistically significant differences in these CIs for each type of study as indicated by non-overlap. To make this comparison, the study group searched the literature to select relevant RCTs. They found 13 nAMD trials, 9 DME trials, and five RVO trials they deemed suitable for comparison.

The investigators found that, for patients with DME, the mean age of the OCEAN patients was statistically significantly higher than that of the RCT patients. In contrast, the sex distribution of the study group in OCEAN was comparable with those in the RCTs for all indications.

Moreover, for nAMD and DME, the investigators found notable differences in baseline visual acuity between study groups in OCEAN and in the RCTs. Mean baseline visual acuity was significantly higher in some RCTs and lower in other RCTs than in OCEAN.

“Across the trials and indications, the results from OCEAN tended to show higher or similar SDs [standard deviations] than the RCT data” in patient characteristics, the OCEAN study group noted. Findings from their demographic study also led them to highlight the complementarity of non-interventional studies and RCTs.

A report on the study, “Demographics of patients receiving intravitreal anti-VEGF treatment in real-world practice: healthcare research data versus randomized controlled trials,” was recently published online in BMC Ophthalmology.

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