Anavex Life Sciences Corp (AVXL)

[nidan7500]

In other words is the dominance of the FDA by BP facilitated by the User Fee Act (PDUFA) since that is what funds the FDA that BP can chase the resources of the FDA down rabbit holes so they do not have the time and resources to divote to promising or even paradigm shifting new drugs of smaller innovative Biopharm Companies and therefore retain their dominant positions in the Drug Industry?

How would Dr Peter Singe analysis the PDUFA dilemma?

Excellent question and yes, you may have identified at least an initial root cause for the continued systemic failures with this process.
You may know that Dr. Senge has initially identified a number of Archetypes for systems which recur in business and nature. These systems repeat with variation and, when diagramed, can reveal the leverage or weakness point for discussion/resolution. In this case you have identified a key weakness...but it is not obvious or easily corrected.

From his book, "The Fifth Discipline", the archetype most likely applicable here is called, " tragedy of the commons". He describes this as, " Individuals use of a commonly available but limited resource solely on the basis of individual need. At first they are rewarded for using it; eventually they get diminishing returns, which causes them to intensify their efforts. Eventually, the resource is either significantly depleted, eroded or entirely used up."

So, consistent w/your observation. If the FDA is used up all resources chasing BP trial path (lets face it, that would be easy to do w/massive resources and influence capabilities available to them). Then what happens, the FDA process becomes saturated w/perhaps incomplete/repeated/weak trial thesis which they are obligated by rule to assess. This sucks up all their resources/time and satisfies political guidance and blows out all time lines. Micro Bio interest cannot sustain themselves waiting in the queue to starve. BP, keeps the system pretty well filled up often chasing rabbits that are incompletely researched (Like multiple attempts at AMYLOID THESIS trials). They sucked up all resources for years and produced continued failures but the BP-political system was happy. Finally, after decades Dr.G. pulled that AD plug, but the problem should have been identified long before his appointment. The fact that he had to kill all Amyloid thesis trials should have been taken as evidence by upper management that they have a broken process. BUT...THE FDA DOES NOT DO HELP.

Problem Early Warning Symptom:

P. Senge

"There used to be plenty for everyone now things are getting tough". My analysis of this, we/FDA have limited resources which have been loaded down w/projects/trials many of which have dubious futures but which can only be removed by running the trial b/c they ticked all the system boxes. And, everyone keeps their jobs, keep the line moving. We can easily see why this current system of trials and who gets in is destined to fail exactly as it has. The emphasis on a solution has to be to require better/stronger science be done before they are even considered for trials. Make the BP do stronger science and insist in changes in the system (like Biomarkers, ERP's, more RWE/RWD before discussion on plans.) Make it a lot more challenging.

IMO, the Precision Medicine process initiatives are clearly designed to get the ball moving down a different/better path. In no case should continued trials(like Amyloid Thesis) be allowed to suck up all the oxygen in the room. The PDUFA w/obvious conflicts as you point out have served only to self reinforce the process now in place. Continued to use a process which could by design go nowhere due to built in constraints. Any decent management staff should have seen this and fixed it.

By any analysis one must conclude the current system is not effective. It would take a lot more time and resources than we have here to resolve every issue. The Precision Medicine initiative should work if it emphasizes biomarkers w/solid RWD/RWE. More powerful Preclinical and clinical investigations need to be established as the place where money and resources gets spent. As Dr.M. has said P2+/3 must be used to verify(demonstrate/prove by objective evidence). Shift the burden so that proof at P3 is simply a formality for regulatory purposes, having already ensured certainty of efficacy through protocol design.