VANCOUVER -- As the FDA more seriously considers including patient-reported outcomes (PRO) as part of its approval processes, a forum it held with Parkinson's and Huntington's disease patients and their caregivers revealed that these groups care deeply about non-motor symptoms, researchers reported here.
During the FDA's Patient-Focused Drug Development Initiative gathering for Parkinson's and Huntington's disease in September 2015, the groups said sleep disturbance, cognitive impairment, and depression and anxiety were some of their most significant symptoms, according to Klaus Romero, MD, of the , a non-profit supported by FDA that aims to improve drug development.
"There are a lot of non-motor features that are important -- and that's obvious, but FDA needs to hear that, because this provides the ammunition to go back and look at how these things are measured right now," Romero said during a poster presentation at the Movement Disorders Society meeting here. "Now we can we go back to the FDA and tell them about the review that we did, and if they give their stamp of approval, that means companies can make use of those tools in confidence, without wondering whether the review process is going to get hung up on whether they used a certain biomarker or not."
Patient perspectives haven't historically been included in drug development, but the tide has been turning at the FDA. The agency held its first Patient-Focused Drug Development Initiative meeting in 2013, and since then.
During the Parkinson's and Huntington's meeting, 260 Parkinson's patients and caregivers attended, along with 110 Huntington's patients and caregivers.
For Parkinson's, the daily symptoms that have the greatest impact on their lives included motor symptoms as well as sleep disturbances, cognitive impairment, fatigue, and constipation, as well as their increasing reliance on others and their inability to perform work activities.
Regarding therapeutics, most said that the benefits of existing medications are limited, often giving way to adverse events and advancing disease -- thus there's a need for drugs that are effective in delaying the onset or slowing of progression, they said. And their ideal drug would, of course, be a once-daily pill that controls all symptoms.
For Huntington's disease, symptoms that mattered most to patients included cognitive impairment, speech impairment, dystonia, depression and anxiety, sleep issues, gastrointestinal issues, neuropathy, and weight loss -- again, many of which fall into the non-motor realm.
Since current treatments don't stop the most disabling disease features from worsening, this group touted the benefits of non-drug therapies including exercise, dietary modification, lifestyle changes, and meditation, and said there's an urgent need for medications that can slow disease progression.
Romero emphasized that subjective aspects of any disease lend themselves to measurement with patient-reported outcomes. Development of pain therapeutics has served as one model, he said, given that these drugs have been approved via subjective outcomes.
Beyond that, however, there are no instances where FDA has approved a drug based on patient-reported outcomes, with the exception of some label claims for asthma medications and certain oncologic indications, Romero said.
But that is likely to change in the near future: "I don't think it's a matter of 'if' [FDA will use patient-reported outcomes]," Romero said. "It's a matter of when."
"The whole field is evolving," Romero continued. "If there's an aspect of the disease that's subjective and it's clinically meaningful, that's perfect for PRO."
The Critical Path Institute is a non-profit organization supported by the FDA and charged with carrying out the agency's , which launched in 2004. The initiative, in turn, is supposed to develop the necessary legal, scientific, and regulatory infrastructure to foster improved drug and device development. The Institute currently has about 15 different consortia focused on various conditions, according to Romero.