FDA Needs Formal Mechanism To Integrate Patient Input, Groups Say

Although FDA says its drug reviewers are benefiting from the patient-focused drug development meetings under PDUFA V, stakeholders say a formal methodology is needed to incorporate patient input into the benefit-risk framework and drug review process.

FDA needs to create a transparent, formal methodology for incorporating information learned from patient engagement, particularly the PDUFA V disease-area meetings, into its drug review process while also alleviating barriers to industry interactions with patients earlier in the drug development process, stakeholders said during a Feb. 19 FasterCures webinar.

The first five patient-focused drug development meetings “have been great,” said Eric Gascho, assistant vice president of government affairs at the National Health Council. “We have reports that have come out of them, but at the end of the day we need to be sure this information is actually being incorporated into the review process and that industry actually feels that there is a reason for them to be incorporating patients into their research process,” particularly regarding the clinical outcomes that will be important to patients.

FDA and industry have made great strides in patient engagement but “we still have a ways to go,” NHC’s Gascho said.

Gascho said the needle has moved quite a bit within FDA and industry in the past five or six years for incorporating patient engagement but “we still have a ways to go.”

Growth In Patient Preference Research

Academics are working to assist in this process, said Kim McCleary, director of strategic initiatives at FasterCures, which sponsored the webinar on benefit-risk framework and patient-focused initiatives created under the latest authorization of the Prescription Drug User Fee Act.

The number of publications on patient preferences for benefit and risk tolerance is increasing, McCleary said. While most are based in the social sciences, there are starting to be a number of publications and disease areas where scientists and academics are working to quantify patient risk-benefit preferences for use by drug developers and regulators in making decisions.

McCleary pointed to a collaboration between the patient advocacy group Parent Project Muscular Dystrophy and Johns Hopkins University to survey the parents of boys with Duchenne muscular dystrophy to understand what treatment benefits they would look for in exchange for trade-offs on risk. The groups have also worked with FDA to help frame the issue from a regulatory standpoint.

The PDUFA V patient-focused drug development meetings are designed to systematically gather patient input on disease burden, available treatments and tolerance for risk in a given disease area or condition. FDA reiterated during the webinar that the questions posed at those meetings are intended to help fill in the first two parts of the new benefit-risk framework used for evaluating products under review – the “analysis of condition” and “current treatment options” sections (Also see "“Patient Voice” Report Puts Chronic Fatigue Symptoms, Treatments In Benefit/Risk Framework" - Pink Sheet, 7 Oct, 2013.).

But stakeholders may not want to get their hopes raised that FDA can create a formal process for incorporating patient opinions into its regulatory decision-making. At a recent Institute of Medicine workshop, Center for Drug Evaluation and Research Deputy Director for Clinical Science Robert Temple said how patients’ opinions influence approvals likely will remain subjective because such views are very individualized and involve several assumptions that would be difficult to fit into a formal system (Also see "Systematizing Patient Views Unlikely, FDA’s Temple Says" - Pink Sheet, 24 Feb, 2014.).

Limits On Industry Interactions With Patients

Gascho also said there are a number of barriers preventing industry engagement with patients, limiting companies’ ability to use and seek patient feedback. “For example, there is a concern that if they speak with patients before the clinical trial phases it might be considered pre-approval marketing,” he said. “We really need to think about how we might be able to remove these barriers.”

Gascho said the National Health Council is looking into solutions that might “dovetail nicely” with PDUFA VI negotiations.

There are some legal limitations on the extent and types of interactions that companies can have with patient groups, Andrew Emmett, Biotechnology Industry Organization managing director of science and regulatory affairs, said in a November interview with “The Pink Sheet.”

These include issues related to confidentially and confidential commercial information that need to be taken into account when talking about a specific development program, as well as limitations about how companies can speak about an investigational drug so as not to be viewed as promoting an unapproved or off-label medicine. “Companies of course are cautious about that and want to be responsible in their communications with patient groups and the general public,” he said.

Emmett said there are opportunities for industry and patient groups to partner after the PDUFA V disease-area meetings to develop new patient-reported outcome instruments and endpoints. Many companies have patient advisory boards or are developing patient registries to better understand the natural history of a disease, he said.

Emmett said he did not know whether companies are engaging patient groups in advance of specific disease-area meetings, but BIO is not doing this because it wants to make sure the meetings are seen as an independent, credible process that is not influenced by industry.

As feedback from patient-focused drug development is incorporated into FDA’s benefit-risk framework, Emmett said it would be helpful for industry and FDA to include this framework in earlier stages of drug development to make sure sponsors and the agency are on the same page around the disease, benefit-risk and current treatment options. This, in turn, “may help inform go/no-go decisions for companies when they’re making their R&D investment.”

Drug Reviewers Find Meetings Helpful

FDA’s drug review staff has found the patient meetings helpful, said Andrea Tan of CDER’s Office of Strategic Programs.

“One thing that’s been unique about this process is the feedback has been unanimously positive and the different reviewers that we’ve worked with, some have been extremely engaged and excited to have these meetings,” she said. “Almost all of them have said that they have learned a lot from these meetings, so I think it’s personally impressive to see how responsive the review staff has been to these meetings.”

This news is likely a good sign since FDA medical reviewers may not know much about the target condition for a product they are reviewing; many are general practitioners reviewing drugs for diseases with which they may not have much experience (Also see "FDA Looking To Patient Advocates To Answer Benefit-Risk Questions" - Pink Sheet, 2 Dec, 2013.).

Gascho was optimistic that the patient-focused meetings will impact disease areas beyond those that garnered one of the lucky 20 spots in the PDUFA V program, something that could help squelch some of the concern that FDA was creating a priority list of sorts for agency approvals (Also see "20 Is The Loneliest Number: FDA Disease Meeting Schedule Leaves Some Worried About Exclusion" - Pink Sheet, 23 Oct, 2012.).

“This is helping us learn how to seek this information from patients,” he said, explaining that the meetings will help create a framework for speaking with and learning from patients and filling out the FDA’s benefit-risk framework for disease areas that don’t go through the formal meeting process.

However, Gascho said it is important that FDA make the processes for patient group communication with the agency outside of these formal meetings clear, and he noted that some groups have more connections with the agency than others.

Tan said FDA is taking steps to make the FDA-patient interaction process more systematic but that it “has a ways to go.” Patients can engage with FDA outside of the patient-focused meetings through the Office of the Commissioner’s Office of Health and Constituent Affairs patient network portal, she said.

FDA also has participated in meetings on patient-focused drug development run by external groups and is open to more of this type of interaction. “We just don’t have the capacity to really put on 7,000 meetings for the 7,000 rare diseases but would be open to exploring if say a patient group wanted to run their own meeting and invited FDA to attend,” Tan said.

When asked if FDA was looking at online patient communities and what it was doing to make sure it was hearing from patients not associated with a specific organization or group, Tan said FDA tries to do outreach to all different kinds of patients. “We do recognize that we are not getting a complete random sample from patients in the U.S. We do our best to make sure as many patients know about these meetings as possible.”

FDA is aware of social media platforms such as Patients Like Me and others and is “still exploring how to best leverage those tools and see how that fits in with the conversations that we are having in the in-person meetings,” Tan added.

Quality Of Life And Real-World Medication Use

Gascho said it’s important that both individual patients and patient organizations interact with the agency, noting that the larger organizations may offer more valuable input. “We realize there are certainly points of input where it might be more appropriate to speak directly to patients and in a lot of cases it might make sense to speak to patient organizations who often can give you a wider view of the entire patient community.”

NHC has developed a patient information tool to help capture patient input. It is composed of three sections: identification of subpopulations; description of disease diagnosis and impact; and description of treatment and management options.

Aspects of the tool that FDA has taken particular interest in include areas that delineate a disease’s impact on social factors, such as the ability to work, the role of family or caregivers in decision-making and the impact of the condition on comorbidities and daily activities, as well as how patients view and use available treatment options.

FDA is “really curious to know how conditions might impact someone’s life. For example, is it impacting the ability to work and support a family? This is something that FDA typically has not had as much information on in the past. … I think often times the actual biological impact on people is sometimes a little easier to understand. So they really need to learn more about how a condition might impact people in their daily life,” Gascho said.

The agency also seems very interested in learning more about how people view available treatment options and patients’ access to these treatments. “There is often going to be a lot of data at FDA about how many drugs have actually been approved,” Gascho said, but the agency is often not aware of which drugs patients actually use.

“Just because there have been products approved doesn’t mean they are actually being prescribed to patients for a whole host of reasons,” he said. So while FDA might understand that there are four or five drugs to treat a condition, if patients aren’t receiving the drugs they aren’t actually treating the condition. “It’s important for people to realize what happens once it actually gets through FDA and how [drugs] will actually get to patients.”

The Pharmaceutical Research & Manufactures of America is also testing a system to collect and share patient perspective data with FDA. PhRMA is funding a Genetic Alliance initiative to help groups representing three diseases collect patient-reported symptoms and life-impact data through website surveys (Also see "PhRMA Wades Into FDA Patient-Focused Data Collection: Website Systems for Crowd-Sourced Info" - Pink Sheet, 6 Nov, 2013.).

Sue Sutter contributed to this story.