We are well aware that changes in pulmonary function occur as Duchenne progresses. In Duchenne, respiratory muscles (including the diaphragm) weaken and it becomes more difficult to take full breaths in, fully expand the lungs, hold full breaths, breath full breaths out, and to cough effectively. And we know that these changes occur first during sleep.
Measures of Pulmonary Function
There are many tests used to demonstrate changes in respiratory function:
Clinical trials that hope to improve pulmonary function include many of these measures of pulmonary function as “pulmonary outcome measures.” But using pulmonary outcome measures creates a whole series of questions we need to clarify.
Addressing the Issues
As such, PPMD and an expert steering committee are facing these questions head on. Thanks in part to support from Santhera Pharmaceuticals, Catabasis Pharmaceuticals, and Pfizer, PPMD will gather experts in Duchenne pulmonary care and evaluation, to discuss these questions in April.
PPMD 2016 Pulmonary Outcomes Meeting Leadership
Asking the Right Questions
Some of the questions we will be exploring at our meeting in April include:
These questions have been important in Duchenne care, but are becoming increasingly more important as industry seeks to show drug efficacy by demonstrating improvements in pulmonary function.
The goals of this “Pulmonary Outcomes Meeting” include:
We will look at the pulmonary function measures that pulmonary care providers and industry are using now. Several natural history data sets have collected pulmonary function measures, and we will discuss how those measures have shown changes throughout the natural history of Duchenne. We will then look at the how measures of pulmonary function have correlated with other areas of patient evaluation (skeletal muscle strength and function, incidence of upper respiratory infections/pneumonia/antibiotic use). We will discuss how pulmonary data is analyzed, and discuss whether data sets can be compared and whether standardized protocols might enhance the reliability of pulmonary outcome measures.
We have invited members of the FDA Divisions of Neurology and Pulmonology to give their views on what they may feel to be appropriate and meaningful pulmonary outcome measures. Pulmonary outcomes collected from a variety of trials will be discussed, as well as novel assessments that might be implemented in future trials (such as home based pulmonary monitoring, diaphragm ultrasound, etc.) and future directions that pulmonary monitoring might lead. A report of this meeting will be published.
It is our hope that this meeting will help to clarify much of the confusion around pulmonary outcome measures. We must begin by agreeing on which pulmonary outcome measures to collect, how to analyze these measures, and the meaningfulness of these measures. If we can agree on these issues, we can begin to demonstrate the efficacy of drugs on pulmonary function and, hopefully, speed up the drug approval process. It’s a lofty goal but, with this panel of experts, we think we are up to the task.