Regulatory and Developmental Aspects of Biomarkers in the Treatment of Ocular Surface Disease.

Abstract

The ideal biomarker would be a simple laboratory or clinical evaluation before treatment, which would predict subsequent therapeutic response. This might include selection of which patients might respond to that treatment. While other disciplines such as neurology and oncology have biomarkers, ophthalmology is limited to one-elevated intraocular pressure as a surrogate for progressive glaucomatous field loss. US law in 2016 required the Food and Drug Administration (FDA) to set up a system to qualify biomarkers. The system now exists-with most validated or pending biomarkers limited to safety and infection. The American Academy of Ophthalmology selected dry eye disease as one of three diseases in which to standardize outcomes in ophthalmology research. There have been a number of biomarkers proposed for evaluating ocular surface disease and its treatment. None currently meets the scientific or regulatory basis for being a valid biomarker-however, additional research may result in validity. Given the FDA's scientific basis, it is unlikely that an unproven biomarker could be used for regulatory approval, even for a "SubPart H" conditional new drug application. Elsewhere in ophthalmology, we know that even patients who share the same disease gene or mutation may differ substantially in penetrance and clinical expression. Thus, it is not unexpected that ocular surface disease, a heterogeneous disease with a variable presentation of signs and symptoms, has yet to have validated biomarkers that reach the level of evidence that allows their use for diagnosis, prognosis, therapy, and for making decisions in drug development.