An important part of the 2012 user fee reauthorization cycle is Congressional efforts to push FDA toward approving drugs and biologics more rapidly. Most of industry and a large number of patient groups agree. Proposals to speed up FDA are already in play.
Since these proposals have a common purpose, it is easy to think of them as alike. However, most are different from each other—in focus, intent, and likely impact on the agency’s existing decisionmaking process. This is FDA Matters’ analysis of why proposals to speed up drug approvals can’t be lumped together and why FDA may support some, but not others.
Is FDA really too slow? Efforts to speed up drug approvals start with an implicit assumption: FDA is approving drugs too slowly. The conventional wisdom is that FDA’s positioning swings over time like a pendulum. FDA allegedly gets "too easy" with its approvals, but then a few years later is faced with a major product recall over safety issues.
The FDA then hunkers down and the pendulum swings toward being slow and rigid. Finally, the bad experience becomes less immediate in the agency's mind and the pendulum swings back toward “too easy” and the cycle starts again.
The FDA mindset. FDA hates this metaphor, but secretly fears it might be true. As a result, the agency has been working toward being more consistent….and less prone to the alleged pendulum swing. Among other things, the agency is trying to publish more official guidances and handle perceived blockages proactively (e.g. prospects for obesity drugs seem to have improved since the failure of three such drugs to gain approval in 2010).
Some of this spirit of change is reflected in the agency’s October 2011 white paper, Driving Biomedical Innovation: Initiatives to Improve Products for Patients. Likewise, as part of the new user fee workplans, FDA and industry agreed to work together, particularly earlier in the development process, so that there are fewer surprises and more approvals.
Proposals for speeding up drug approvals. Improving the existing accelerated approval process is the goal of the Faster Access to Specialized Treatments or FAST Act (HR 4132) and section 301 of the Transforming the Regulatory Environment to Accelerate Access to Treatments or TREAT Act (S. 2113).
Accelerated approval allows surrogate endpoints as the basis for demonstrating efficacy. FDA uses this example: “instead of having to wait to learn if a drug actually can extend the survival of cancer patients, the FDA might now approve a drug based on evidence that the drug shrinks tumors because tumor shrinkage is considered reasonably likely to predict a real clinical benefit.”
The two bills would broaden the means to demonstrate clinical benefit by encouraging use of emerging scientific methods and tools and allowing a wider range of surrogate and clinical endpoints. The bills would explicitly codify the accelerated pathway in law.
A different approach is taken in the Advancing Breakthrough Therapies for Patients Act or the Breakthrough Act (S. 2236). This bill would “provide more flexibility when a drug or treatment shows dramatic responses early in development, while still ensuring drug safety and efficacy. For patients, this proposal would allow FDA the ability to move towards more innovative clinical trials, such as minimizing the number of patients enrolled in trials and shortening the duration of trials, when scientifically appropriate.”
This reflects a reality: FDA often feels constrained in situations where common sense dictates special handling. An example might be a new melanoma treatment that was approved in August 2012, after receiving significant assistance from FDA to move the drug forward rapidly. However, after reading an earlier NY Times article, it is easy to imagine that FDA might have been even more flexible, but felt constrained.
Finally, some commentators have included former FDA Commissioner Andrew von Eschenbach recent Wall Street Journal article in their discussion of “speeding up FDA approvals.” He advocated “creating FDA pilot programs to bring promising therapies to patients more quickly by allowing them to be approved based on safety, with efficacy to be proven in later trials.”
Speculation on FDA’s position. FDA is certain to oppose Dr. von Eschenbach’s proposal if offered as a legislative amendment. However, FDA is still deciding its position on FAST/TREAT and the Breakthrough Act.
In response to a Congressional question, FDA spoke favorably of the Breakthrough Act. The key is that FDA is given discretion to provide more rapid and higher level process, but is not directed to change the standard of proof or the meaning of efficacy or safety.
FDA has been more hesitant about FAST/TREAT. Informally, it opposed a prior iteration because, among other things, it lowered standards by not requiring prior validation of a surrogate endpoint. My understanding is that FDA is considering whether its concerns have been addressed by these later versions of the bills.