Application of machine learning methods to bridge the gap between non-interventional studies and randomized controlled trials in ophthalmic patients with neovascular age-related macular degeneration.

Purpose: The effectiveness of intravitreal anti-vascular endothelial growth factor agents is usually lower in real world settings compared with randomized clinical trials (RCTs), often limiting the use of real-world evidence (RWE) in regulatory and healthcare decisions. The current analysis aimed to develop and validate an algorithm to explain the difference in outcomes between RWE studies and RCTs in patients with neovascular age-related macular degeneration.

Methods: The algorithm was developed using ranibizumab real world data (RWD) from the US and validated on Australian and UK RWD. A decision model was developed using machine learning principles, in which the model learns how to partition the most influential factors (out of 59 variables) so that they maximally relate to the change in visual acuity (VA) over 12 months.

Results: The algorithm identified baseline VA <73 Early Treatment Diabetic Retinopathy Study letters, presence of baseline subretinal fluid, and administration of three loading doses by Day 90 from drug initiation as the characteristics with the greatest impact on VA at month 12. When applying the different criteria, RWE outcomes became similar to those obtained in known RCTs.

Conclusion: Machine learning techniques can be used to classify real world cohorts and identify subsets of patients who benefit to the same extent as that reported in RCTs. This methodology may support the translation of clinical trial findings to treatment performance in the clinical practice setting.