Next Steps for Patient-Centered Drug Development: Room for More Input, With Limits

Patient advocates are pushing the Food & Drug Administration to take the next step in the agency’s patient-focused drug development initiative and more directly incorporate the patient experience into regulatory decisions. While that’s a welcomed ask, FDA officials say, it’s not as easy as it looks.

FDA Center for Drug Evaluation & Research Director Janet Woodcock, MD, acknowledges that the agency has a lot to learn from patients about drug development and regulatory policy.

“We understand that people with chronic diseases are experts in that disease, as far as the symptoms and the impact on quality of life, and what might be acceptable trade-offs on risk and uncertainty,” Woodcock said during her keynote address at TheRPM Report’s annual FDA/CMS Summit for Biopharmaceutical Executives in December. “We hear from patients about this all the time.”

But the challenge for FDA, Woodcock said, is incorporating that knowledge in a way that accurately informs regulatory decisions. “How can we meaningfully collect that knowledge in a rigorous manner, given there’s a spectrum of opinions and a spectrum of disease burden in any given disease?”

“We’ve had a lot of suggestions over the years that we get one patient and put them into meetings” with the FDA review team. “We do that sometimes. But one person does not represent the spectrum of the disease,” Woodcock said. For example, if an individual is well enough to participate in the process, “they really may not reflect the actual impact of the disease.”

Office of New Drugs Director John Jenkins, MD, echoed those remarks in a separate keynote address at the FDA/CMS Summit. “How do you gain the ‘patient perspective’ when you’ve got hundreds, if not thousands or millions of people with a particular disease,” he asked. Multiply that times the number of diseases and conditions, and “it’s hard to figure out how to integrate that into the process.”

Patient advocates have found some success in engaging FDA during the formal patient input meetings held as part of the FDA Safety & innovation Act’s patient-centered drug development initiative. Of the 20 patient-focused meetings planned by FDA this user fee cycle, 11 have been held so far, with five additional meetings slated for the remainder of fiscal year 2015. (Also see "Disease-Of-The-Quarter Club: FDA Plans 20 Patient Network Meetings Over Five Years" - Pink Sheet, 18 Jun, 2012.)

Those patient-input meetings have been labeled by patient advocates as a “good start,” but stakeholders want to better understand how the information shared during those meetings is used, and how they can directly inform regulatory decisions.

Woodcock acknowledges that sentiment. The discussions are “going well,” she said, “but it’s clear they reflect a broader trend that is gaining traction, and people want to know the next step.”

Wanted: A Systematic Approach

Stakeholders have been vocal about what those “next steps” should be, and there are a few specific examples of how patients have played a direct role in review decisions. (Also see "Patient-Focused Drug Development High On Industry’s List Of PDUFA VI Tweaks" - Pink Sheet, 29 Sep, 2014.) Patient groups have hosted briefings with review teams on specific diseases outside of the 20 patient-input meetings, and consulted FDA on the relevance of clinical trial endpoints for BioMarin Pharmaceutical Inc.’s Vimizim. (Also see "Patient Advocacy And PDUFA VI: Next Steps Could Include Involvement In Reviews, More Scientific Briefings for FDA Staff" - Pink Sheet, 18 Jul, 2014.)

But patient advocates want a more systematic approach to their involvement in drug development. That desire is prominently reflected in the House Energy & Commerce Committee’s first draft of the “21^st Century Cures” legislation, which begins with a section on patient-focused drug development that would direct FDA to use patient-experience data in constructing a risk/benefit framework. (Also see "New Rx Approval Standards, Faster Pathways Offered In Cures Legislation" - Pink Sheet, 2 Feb, 2015.)

FDA, however, seems more comfortable with the qualitative feedback about symptoms and disease burdens, which can then help broader or strengthen the endpoints for trials.

One area where patients can be particularly useful, Jenkins said, is by explaining the endpoints that are most important to study in clinical trials for their particular disease or condition. “Maybe we need to move to endpoints that affect the symptoms and daily lives of patients and move away from endpoints doctors focus on,” he said.

Jenkins even suggested a possible commercial advantage to including patient-reported outcomes in clinical trials: “a greater impact and a greater relevance to the patient when they hear that a new drug has been approved. It’s not based on some laboratory measure that it’s not so meaningful for them, but on a PRO for symptom improvement or activities for daily life.”

FDA officials have spoken publicly about the importance of patient-reported outcomes, but drug sponsors have been slow to routinely use PROs when designing registration trials. FDA doesn’t require sponsors to consider PROs in clinical trials, and historically, hasn’t done much to encourage their use. But there are signs that sentiment is turning around, at least in certain drug review divisions. (Also see "Getting With The PRO-gram: Making Patient-Reported Outcomes Work" - Pink Sheet, 24 Nov, 2014.)

Jenkins also suggested that patient representatives could use their expertise to help FDA draft guidance documents to industry. “I think that’s a pathway that could be fruitful to help get them to help us focus and collate all the information that they can put forward as a suggestion of how the agency might want to formulate its own guidance.”

He pointed specifically to Parent Project Muscular Dystrophy’s submission of a draft guidance for drug development in Duchenne muscular dystrophy as an example of how patients can be directly involved in the regulatory process. FDA is “incorporating” the issues outlined in PPMD’s draft “into our thinking as we’re working to issue an agency guidance in that area.”

Overall, patient-centered drug development has been a “great initiative,” Jenkins said. “We would like to think that we’ve always been patient-focused in our oversight and regulation of drug development. But clearly, there’s a lot of room for more input from patients into the drug development and approval process. I think we welcome that.”

Woodcock agreed, but cautioned that there is work to be done.

“Many patient groups and non-profits are getting involved in evaluating these issues, and we have to assess how such input can be translated to acceptable endpoints in drug development guidance,” she said. “We’re going to have to think of a framework of translating that patient input – developing it, collecting it and then translating it to actionable steps for drug development.”