FDA And Pharmaceutical Companies Welcome Patient Voices To New Drug Development –- But Will It Last?

It may not be obvious from your medicine cabinet, but patients have more say than ever in the way drugs are developed in the U.S. Pharmaceutical companies and the government now welcome patients’ thoughts on their diseases, symptoms and treatment options at virtually every stage of the process.

Many stakeholders from health policy experts to physicians to patients’ groups are broadly in support of this shift. But the U.S. Food and Drug Administration isn’t quite sure how to handle the resulting flood of information, anecdotes and opinions that comes from a patient-centered focus. As a result, there is ambiguity about if and how patients’ feedback will be incorporated into the process by which new medicines progress from an idea in a lab to a finished product on the shelf.

In particular, the FDA offers little guidance on how so-called “patient-focused outcomes” might be used to support a new treatment proposed by a drug company, or whether such results eventually could be published on a label next to side effects. Companies eagerly have echoed the FDA’s patient-centric mindset, but without clear instructions on how to standardize and incorporate patient opinions it may be difficult to translate that enthusiasm into better medicines or higher sales.

“I believe the whole patient-centric movement really signals a pretty profound change but I also have this fear that if we don't implement this correctly, we'll lose our patience,” said Ken Getz, director of sponsored research at Tufts Center for the Study of Drug Development.

Meanwhile, the FDA is working to renew the Prescription Drug User Fee Act (PDUFA), which permits the agency to collect user fees from major drug companies. It could use these funds to develop meaningful ways to incorporate patient opinions into clinical trials and eventually product labels -- a move requested by the industry group Pharmaceutical Research and Manufacturers of America (PhRMA) during a public comment period that ended Monday.

“We have heard from pharma and bio that -- and they’re using the term ‘science of patient input’ -- is one of the most important items of discussion for the reauthorization of PDUFA,” said Theresa Mullin, director of the Office of Strategic Programs at the FDA Center for Drug Evaluation and Research. “They're identifying this as a high-priority area.”

In the past, clinical trials have attempted to capture similar information from patients such as how tired they feel or whether they are able to complete basic tasks such as getting dressed in the morning through questionnaires or asking people to rank their sleepiness on a 10-point scale. But such tools must be validated to confirm any blips in the results are a consequence of the treatment rather than random chance. Some pharmaceutical companies have begun tracking patient-focused outcomes with tools and instruments during clinical trials, but only on a pilot basis and the vast majority have not been validated.

“What we really need for patient experience data is a set of standards and appropriate ways to collect that data and submit it to the FDA,” said Gregory Daniel, director for evidence development at the Brookings Institution’s Center for Health Policy.

While the FDA offers some guidance on how to verify devices and submit outcomes as part of a clinical trial, it has yet to spell out exactly how this data might be used during a drug’s evaluation. Companies say the agency needs to more clearly define the standards they require for patient-focused outcomes to become a true measure of a drug’s success.

“This will be an important element of us in moving forward to try to get agreement with the FDA on how to validate these endpoints, and how to move forward with labeling,” said Vas Narasimhan, global head of development for Novartis Pharmaceuticals. “And I'm not convinced the FDA actually knows the answer.”

Dr. Anne Beal, who was hired to fill the newly created position of chief patient officer for Sanofi in 2014, would love to see the agency offer a list of best practices on how to incorporate patient-focused outcomes into clinical research. She formerly served as deputy director and chief of patient engagement at the nonprofit Patient-Centered Outcomes Research Institute, and says the industry is actively looking for opportunities to develop and share this research.

Mullin at the FDA is well aware of these requests. She said guidance from her agency likely will come as a series of steps for the industry to follow to test and verify instruments or tools to assess these new outcomes.

David Gortler, a former FDA senior medical officer and drug safety expert at FormerFDA.com, said that promise is hard for drug companies to hang their hats on. If the agency can’t offer the industry clear guidance on how to proceed with including patient-focused outcomes in clinical trials, the movement could fall flat.

“My main gripe with it is that talk is cheap,” he said. “The FDA, they've got to put their money where their mouth is.”

Perhaps the most important symbol to date of the FDA’s commitment to this ideal is the creation of patient workshops focused on specific diseases the agency hosts at its campus in Silver Spring, Maryland. Any patient who wishes to discuss a condition and symptoms or bemoan the lack of treatment may do so during these meetings.

All that information winds up in a report called the “Voice of the Patient” that is posted to the FDA’s website and which contains details such as a narcolepsy patient who described feeling “brain fog” and another who underscored the disorienting aspects of the disorder by saying he once placed the TV remote in a box of fish sticks. Since 2012, the FDA has held 14 workshops.

This information does not naturally lend itself to the scientific rigor required to scrutinize a drug in a clinical trial, but Mullin said it provides important context. The agency directs advisory committee members who rule on new medicines to these reports if they are relevant to treatments they are considering.

While he admires the sentiment, Gortler also said this laser-like focus on patients may not ultimately prove useful to companies and the agency unless there is a standardized way of incorporating the information it yields.

“Too much data is bad as well,” he said. “When you have too much information to look at, it can be overwhelming, add costs to the drug development process and be counterproductive in that it will actually take even longer to approve the drug.”

Keeping Patients In Trials

Pharmaceutical companies’ enthusiasm for the patient-centric shift has been deafening. Sanofi and Pfizer have rolled out patient engagement teams. Earlier this year, Novartis issued a Declaration for Patients, which includes a pledge to ask patients to provide input into clinical trial design.

“We've really been reflecting quite a bit on how we can respond to the needs of patients and make patients the center of everything we do,” Narasimhan said. “We're trying to look at it across the drug development process from when we first conceive the trial through the end.”

But pharmaceutical companies also are interested in pulling patients into the drug development process for another reason -- they struggle to recruit patients and keep them enrolled in clinical trials.

“Our recruitment and retention rates are the worst they’ve ever been in history,” Getz said.

By inviting patients into their offices for a focus group before a trial starts, they may be able to tweak its design to make it more patient-friendly and increase the likelihood participants will stick it through. Since pharmaceutical companies spend an average of $7,600 on recruitment and retention efforts for each patient in a trial, it’s worth it to invest in measures that will keep them there. The government is in support of this effort -- Congress established the Patient-Centered Outcomes Research Institute through the Affordable Care Act partly to fund clinical trials that ask patients to weigh in on trial design.

Getz has heard anecdotal evidence from several companies that suggests involving patients in the clinical trial process improves retention but believes “it’s too early to say” whether the strategy will stick. He cautions this push for patient-centeredness may not last if it doesn't result in savings or if the FDA doesn’t create a way for pharmaceutical companies to validate and submit this data for consideration.

“Unless these patient-centered approaches deliver a return on investment, many of these initiatives will go away,” Getz at Tufts said.

Gortler is skeptical the FDA and pharmaceutical companies can figure out a way to assemble the wave of patient data collected in workshops and by companies into a meaningful way for the drug development process.

“The big thing is whether the FDA will or will not use that data as part of their evaluation process. I'm not convinced they could,” he said. “I think it sounds good to keep the consumer happy. I don't really know what the end game is or what they expect other than to please consumers who know nothing about the scientific process or the drug development process.”

Glen de Vries, president of the health technology company Medidata Solutions, said regardless of whether data is considered by the FDA, patient-focused outcomes have a role to play in the pharmaceutical industry. They could even help companies boost sales of a drug. Patients may be more likely to purchase or stick with a treatment if it can relieve the symptoms they worry about most even if those symptoms are different from the ones that the FDA studied in a review.

Narasimhan at Novartis also is optimistic even if it's not yet clear how the FDA intends to move forward.

“I think there’s a commitment on both sides to really try to work this through,” he said.