Is the FDA doing enough to incorporate the patient perspective in the drug review process? This was the key question considered at a panel of regulatory experts held at last month’s annual BIO International Convention in San Diego. The consensus: while FDA deserves high marks for effort, both in reconciling the diversity of patient organization views and interpreting the often vague stipulations to engage found in the 2012 FDA Safety and Innovation Act (FDASIA), it is not enough.
More must be done to institutionalize the relationship, particularly in defining medical need from a more patient-centric perspective. That requires setting metrics to raise the bar in demonstrating how patient engagement actually shapes and drives FDA decisions, especially around the critical underlying construct of benefit-risk, and spilling over to areas like clinical trial design, marketing authorization, or labeling updates to include patient-reported outcomes.
The law itself is fairly straightforward. As enacted by Congress, FDASIA, specifically in its section on creation of a Patient Focused Drug Development Program, mandates the FDA pursue three broad objectives in liaison with the patient community. These are (1) including a patient perspective on disease severity and medical need as part of the NDA advisory and review process; (2) establishing a framework to allow patient representatives to participate in meetings with investigators, advisory panel members and product sponsors; and (3) initiating a new work stream to categorize, clarify and make transparent FDA actions relating to risk-benefit assessments of individual drugs.
The centerpiece of FDA implementation efforts to date is synthesizing feedback from advocates on what matters to patients in 20 different disease areas. These “voice of the patient” surveys are designed to collate patient testimonial experience in each disease area, which are then synthesized in a benefit/risk grid – fully reflecting the patient perspective – and scored for each disease. Eight of 20 such reports – covering cancer, HIV, chronic fatigue, and sickle cell anemia, among others – have been completed. All the BIO panelists said the reports were thorough, well designed and thus had value, even though how these actually shape actions at the advisory committee level and other key markers toward product approval remains unclear.
Panel moderator David Verbraska, Vice President for Regulatory Policy and Intelligence at Pfizer, noted the FDA stood at an “inflection point” in transitioning from simply engaging with patient groups to demonstrating how patient needs and outcomes rest at the center of drug review, based on clear metrics understood by all. As FDA tries to work out the finer points of the law, Pfizer relies on a simple metric in advancing the patient perspective. “Our goal is to innovate in bringing new therapies to patients that significantly improve their lives. We leave it to each patient to define what ‘significantly’ means, based on their own unique experience – it could be in helping to establish the right endpoints in a trial or shaping a post-marketing approval study that tracks safety and side-effect profiles.”
At the FDA, however, engagement with the patient is still more of an experiment, with highly variable expectations coming from each side – and industry is often caught in the middle. “Patient groups will say they desire more contact, or that things are not moving fast enough at the FDA for them. We then have to ask what level of involvement do you want, and to what end?” No one yet has a definitive response to these questions.”
Instead of having to constantly reframe the discussion, Verbraska says what the industry needs is a clearly articulated pathway to collaborate with patient groups in informing and shaping decisions on market authorizations from the FDA.
The panel – which included, in addition to Verbraska, Andrew Emmett, Managing Director for Scientific and Regulatory Affairs at BIO; Marc Boutin, Chief Operating Officer of the National Health Council, and Kimberly McCleary, Director of Strategic Initiatives at Faster Cures – suggested a number of improvements to the “Voice of the Patient” process, as follows:
Include three key cross-practice measures of patient vulnerability — fatigue, pain and poor cognition — in each patient survey. Any new therapy should show it can mitigate or slow such symptoms. Including these metrics would end up improving the design of trials, with appropriate endpoints to better pinpoint overall outcomes.
Highlight risk-benefit indicators across a staged five platform continuum, covering drugs, devices, diagnostics, delivery and access. Benefit should be found to be distributed across all five platforms.
To promote knowledgeable patient engagement, build more in-house capabilities on the FDA process within patient groups. “There is a tremendous lack of understanding among these groups on how the FDA bureaucracy actually works,” said Kimberly McCleary of Faster Cures. More training and outreach can help remedy this.
Address the representativeness gap among various patient constituencies. Groups invited into the “voice of the patient” process need to have “crowd credibility” along with the reach to ensure that their input is relayed back to the wider community. One way to extend representativeness is for the FDA to focus more on quantitative tools and measures in gathering feedback rather than the current emphasis on qualitative analysis based on a limited number of contacts. It was noted that only 20 patient representatives were present at the patient voice event on lung cancer – in person meetings are challenging to scale, so what other ways can the FDA get the word out?
Perhaps the biggest area for improvement is making these contacts something more than an episodic encounter. “Where is the pull-through that takes this work and applies it directly to key agency goal posts like the integrated pathway applications or breakthrough authorizations?,” asked the National Health Council’s Boutin. “Is there is a vehicle that makes it simply for industry to incorporate this input into its own development cycle plan?”
Boutin rates the FDA performance on patient engagement a “promising but marginal two out of ten,” largely because it has so far failed to try state-of-the-art tools for engagement like focus groups, peer jury exchanges, crowd sourcing, or conjoint/behavioral analysis. “The FDA is relying on a tactical approach without first defining a strategy,” said Boutin. “The pregnant question for patients is: what is the end game?”
No one on the panel expects these basic issues to be resolved overnight. Improvements are likely, but the pace will be gradual. Ironically, the legal process will compel attention to the patient perspective, as FDASIA and its companion, PDUFA V, require a three year implementation plan with periodic progress reports from the FDA on the patient focused drug development provisions. It’s a full employment guarantee – for both the regulator and the regulated.