Nothing About Us Without Us— this mantra lies at the heart of Fighting Blindness, especially our advocacy work. This phrase is particularly important in vision research. We should be involved in the research process, providing information to scientists about how our vision loss affects us and what it is we want from a therapy.
One way of doing this is by advocating for patient reported outcome measures and patient relevant endpoints in clinical trials. We want clinical trials to measure things that are important to us and for participants to be able to give feedback on what they experience.
An example of one clinical trial that effectively used a good outcome measurement was outlined at the recent Retina 2016 Public Engagement Day. Dr Daniel Chung from Spark Therapeutics first gave an overview of the development of the gene therapy to treat inherited retinal diseases caused by the RPE65 gene; this includes some forms of Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). He then explained how they developed a test to measure functional vision, the vision we use day to day for different tasks.
This test, the multi-luminance mobility test (MLMT) is a maze that assesses a person’s mobility. It encompasses aspects of visual field, visual acuity, light perception and contrast sensitivity. The MLMT is a grid of arrows which a participant must follow, stepping over and around obstacles to reach a door at the end.
One of the first things that causes a problem for people with RPE65 diseases is difficulty seeing in dim light, so the participants in the Spark phase 3 trial were asked to complete the maze at different light levels. The levels go from one lux which is like a moonless night, to 400 lux, like a very brightly lit office.
For each participant they first found a light level the person could pass the test at and a light level they would definitely fail the test at, this was different for each participant. People completed the test at both of these light levels again after they received the gene therapy intervention, they were asked to do this in a certain time frame. The change in the number of light levels was used as a determinant of how much change there was in vision between baseline, or before intervention, and after intervention.
Dr Chung finished his presentation by showing a video of one of the participants going through the maze at a low light level before and after she received the therapy. Before the trial intervention, the participant bumped into obstacles and went off course. After receiving the therapy she walked correctly through the maze, didn’t bump into anything and opened the door at the end.
Spark Therapeutics found this performance based testing very effective at measuring functional vision. They are now in the process of making a submission to the Food and Drug Administration (FDA) to have the gene therapy approved so that it can go on the market in the US. They plan to follow this with a submission to the European Medicines Agency (EMA) to gain market approval here.