Friday Flailing: Medical Gasses and the Law of the Excluded Middle

Buried

Aristotle never actually said "principium tertii
exclusi", mostly because he didn't speak Latin.

under the mass of attention and conversations surrounding the ACA last week, the FDA Safety and Innovation Act (FDASIA) contained a number of provisions that will have lasting effects in the pharmaceutical industry.  What little notice it did get tended to focus on PDUFA reauthorization and the establishment of fees for new generic drug applications (GDUFA).

(Tangent: other parts of the act are well worth looking into: NORD is happy about new incentives for rare disease research, the SWHR is happy about expanded reporting on sex and race in clinical trials, and antibiotic drug makers are happy about extra periods of market exclusivity.  A very good summary is available on the FDA Law Blog.)

So no one’s paid any attention to the Medical Gasses Safety Act, which formally defines medical gasses and even gives them their own Advisory Committee and user fees (I guess those will be MGUFAs?)

The Act’s opening definition is a bit of an eyebrow-raiser:

(2) The term ‘medical gas’ means a drug that is--

‘(A) manufactured or stored in a liquefied, non-liquefied, or cryogenic state; and
‘(B) is administered as a gas.

I’m clearly missing something here, because as far as I can tell, everything is either liquefied or non-liquefied.   This doesn’t seem to lend a lot of clarity to the definition.  And then, what to make of the third option?  How can there be a third option?  It’s been years since my college logic class, but I still remember the Law of the Excluded Middle – everything is either P or not-P. 

I was going to send an inquiry through to Congressman Leonard Lance (R-NJ), the bill’s original author, but his website regrets to inform me that he is “unable to reply to any email from constituents outside of the district.”

So I will remain trapped in Logical Limbo.  Enjoy your weekend.

DDMAC to weigh in on trial design?

The FDA Law Blog has an incredibly interesting entry regarding last week's Untitled Letter from the FDA's Division of Drug Marketing, Advertising, and Communications (DDMAC) to Novartis.

The letter, regarding a detail aid for Novartis's Focalin XR, accuses Novartis of making "unsubstantiated superiority claims" for Focalin XR in comparison to Concerta. What is interesting -- and completely new as far as I can tell -- is that the claims DDMAC are taking exception to are, in fact, primary endpoints of two controlled clinical trials:

Treatment for ADHD consists of symptom relief over an extended time period; thus, ADHD medications must control disease symptoms over the entire treatment course. However, the referenced clinical studies only focused on one specific time point (2 hours post-dose) as the primary efficacy measure in the treatment course of Focalin XR and Concerta. By focusing on the 2 hour post-dose time point, the studies did not account for the different pharmacokinetic profiles and subsequent efficacy profiles associated with Focalin XR and Concerta over the entire treatment course.

So, in essence, DDMAC appears to be taking exception to the trial design, not to Novartis's interpretation of the trial results. This would seem to be a dramatic change in scope.

I am not familiar with the trials in question -- I will post an update with more information shortly. Of special interest to me would be to understand: Were these pivotal trials that played a role in Focalin XR's approval? If so, did the FDA review them in a Special Protocol Assessment (and therefore are two distinct branches of FDA providing divergent opinions on these endpoints)?