The following is information from an informal Q&A session with parent advocates:

“I read through the discussion topics but it isn't clear to me what they would do with our answers. Seems like it is mostly about life with an affected person.”

FDA wants to hear 3 things:

First what are the mosttroublesome aspectsof your disease associated with the neurological manifestations. They want to make sure when clinical trials are investigating the safety and effectiveness of new treatments the trials are evaluating the impact of the treatment on the symptoms that are of most important to patients. And the most important people to hear from regarding which symptoms are most troublesome are the individuals constantly dealing with the symptoms.

Second, FDA wants to get a handle on thedegree of need. How much is your quality of life impacted by these symptoms. This will help FDA a lot as they are developing the benefit risk matrix. The greater the need the greater the regulatory flexibility. If a patient has a need that makes their life really difficult, then the patient is willing to take a lot more risk taking a drug that may or may not help them, and may have side effects. Cancer is a great example, for a woman with early stage breast cancer thedegree and robustnessof evidence confirming the safety and effectiveness needs to very convincing, FDA are willing to tolerate little doubt when determining the benefit risk ratio, whereas, if the same patient has progressed to stage IV breast cancer the degree of risk for the patient and the degree of risk FDA is willing to take determining approvability is vastly different for a patient with few months left to live.

Third, FDA wants to hear if a disease has acurrently approved treatment what are the drawbacks. Here PKU is a great example. The diet is so horrible many adult patients refuse to take it. So this translates into FDA determining if another treatment is developed for the same diseases, is the 2ndtreatment considered fulfilling an unmet medical need. This is a big deal from the reg perspective, Not only is it 4 months shorter review time for an unmet medical need, but more importantly thedegree and robustnessof evidence confirming the safety and effectiveness for an unmet medical need is far less.

“It isn't clear to me how our answers will be adapted into change on their side. Any thoughts on that?”

FDA are saying we want to learn. If they want to learn, this means they are saying we recognize and admit we do not know. They are in the drivers seat, it would be good if the driver knew how to drive and if the driver knew how to get from A to B. There are multiple ways the info can be used:

  1. FDA becomemore informed about the severityof the diseases and the impact on day-to-day living and the desperate need for effective treatments
  2. Moreinformed about the degree of unmet medical need, thereby impacting the benefit/risk ratio and the importance of getting a treatment available for patients
  3. FDA are naturally risk averse, and Congress and Public Citizen is adding fuel to the fire putting them on the guillotine when there is a safety issue with an approved product. However, FDA are somewhat less risk averse in the face of desperate need. This is the opportunity for the pts to prove how much is that need.
  4. FDA has limited resources. FDA will place the most resources on the greatest needs, and those that are not a great need will always be at the back-of-the-pack. The resources could be faster reviews, generation of guidances or more attention to meetings on development of a specific drug. The perfect example of this is DMD. The DMD patient organization has successfully got the attention of the hill and the attention of FDA. It sounds like FDA are collaborating with the DMD pt orgs trying to figure out what is the best and fastest way to get a drug on the market. The DMD Patient Grp successfully convinced FDA we have a desperate need and you need to exercise your flexibility to help address our need. Do you think it would be worth collecting up all the patients we know who are planning on participating in the June 10thmeeting to hear from Pat Furlong what she felt has got them to this point. I know there is the Sarepta situation, and the DMD Policy meeting on Dec 12th. But speaking up and telling FDA these are our needs, our needs are desperate will get the attention of FDA and what can FDA do to move along/collaborate on treatments in development or for the future INDs for molecules currently in research.
  5. Another example of the power of these meetings is the Chronic Fatigue Syndrome Patient-Focused meeting in April 2013. This was the first formal patient-focused meeting. 11 months later FDA came out with a draft guideline. Eleven months is very fast based on precedence!. But more important, now not only is there a stake in the ground, it starts the conversation but even more importantly it is actually more flexible than most guidances I have read. The majority of the guidance discusses developing a tool to measure patient reported outcomes (PROs). There are 5 main steps to this process and multiple minor steps, it can take 2 to 5 years and millions of dollars. At least per the draft guidance there is a lot more flexibility in the degree and robustness of date required and flexibility in substituting other data to speed up generation and qualification of the tool.
  6. Finally FDA are obligated per the law to report back to congress what they heard and what actions they have taken as a result of what they heard.