Researchers Query FDA About Updating Requirements For Drug Approval

Researchers from the National Institutes of Health's National Eye Institute (NEI) and major US universities and research centers met in a roundtable discussion with FDA representatives before an audience of their peers on November 28-29, 2006 in Washington DC.

The discussion among the 30 participants focused on endpoints and clinical trial strategies for evaluating new treatments for age-related macular degeneration (AMD), diabetic retinopathy and other severe retinal disorders.

The exchange is the subject of "Report from the NEI/FDA Ophthalmic Clinical Trial Design and Endpoints Symposium," an article in the February 2008 issue of ARVO's peer-reviewed journal, Investigative Ophthalmology and Visual Science. The authors are Karl G. Csaky of Duke University Medical Center, Elaine A. Richman of Richman Associates and Frederick L. Ferris III, of NEI.

The FDA currently recommends that clinical study sponsors compare changes in visual function (measured on a visual acuity chart of letters and numbers) as a primary endpoint in assessing the effect of a new compound for treating a disorder of the eye.

Many scientists feel that the FDA parameters may not be sensitive enough for studying diseases that progress very slowly or for studying the effect of new anti-VEGF agents for treating AMD. They query whether new technologies could more efficiently detect a treatment's effectiveness, thereby hastening the translation of clinical trials into better treatments in the doctor's office.

Such new technologies include optical coherence tomography (OCT), a scanning technology that maps, in 3-D, the minute hills and valleys of the retina.

Scientists suggested the FDA consider other endpoints, like OCT-detected changes in the thickness of the retina or the disappearance of problem blood vessels.

The FDA position is firm yet open. FDA representatives reminded researchers that the FDA sets a high bar for new drug approvals.

The agency might consider a lower bar and different endpoints for clinical trials, provided the degree of risk to the patient is correspondingly smaller and the trial sponsor is able to justify the clinical relevance of the new endpoints.

The FDA representatives also explained several new standards for drugs when two products are used in combination (called combination products or multi-agent products).

The report also reflects discussions about drug safety, post-marketing drug surveillance between eye study designs, mechanisms for obtaining and substantiating data for retinal disease post-marketing, and whether statistically significant differences in visual function outcomes are clinically important.

The symposium was supported by the NEI. It evolved from a series of meetings between members of the eye and vision research community and the FDA Center for Drug Evaluation and Research (CDER).

Symposium co-hosts were Janice M. Soreth, MD, Director of the Division of Anti-Infective and Ophthalmology Products of the CDER, and Karl G. Csaky, MD, PhD, then an NEI senior investigator. ARVO managed the symposium.