Why the Fuck?

Sorry about that; a@hackingla.com and I sent you email :-)

I was considering trying to make custom pro-biotics but the cost are extreme, with that said; this is still an area I am very interested in. I have reason to believe that probiotics custom tailored to the patient could be an order of magnitude more effective.

Lot of important points to engage there, and generally agree with the spirit of the comments. I think many biotech startups would instantly take a deal that gave them and their patients the ability to opt-out of FDA, in exchange for some demonstration that they aren't using public funds (e.g. committing to not use some fraction of the research literature, ineligibility for all govt grants, etc.).

Regarding patents, they are a form of artificial scarcity on the sales end. Regulation is a form of artificial scarcity on the R&D end. That's why regulatory affairs and IP are the two most important departments in any pharma company.

It's useful to think about what the pharma industry would look like with no FDA and no IP protection. It'd look a lot like food, energy drinks, or supplement manufacturers, making commodity products with marketing as the primary source of margin. Generic drug manufacturers are a good first step towards this; we'll see more of this in the near future with the pharma cliff and end of many major drug patents.

Incidentally, the intersection between regulation and IP produces some extremely bizarre behavior:

http://www.fda.gov/downloads/Drugs/.../Guidances/ucm079342.p...

  This guidance is intended to provide industry with 
  information on how the Food and Drug Administration (FDA) 
  is applying the 180-day generic drug exclusivity provisions 
  of the Federal Food, Drug, and Cosmetic Act (the Act) in 
  light of recent court decisions. The guidance
  addresses the issue of the elimination of the "successful 
  defense" requirement, which required an abbreviated new 
  application (ANDA) applicant to be sued for patent 
  infringement and to prevail in the litigation to receive 
  the 180-day period of marketing exclusivity.

How crazy is that? For many years official FDA policy was that a generic maker had to actually be sued for patent infringement - and win in the lawsuit - as the condition for receiving a 180-day monopoly!

I can get into the duct-tape upon duct-tape that led to this bizarre state of affairs, but think about how perverse it is that the FDA was telling companies to break patent law (or at least risk a civil lawsuit) as a matter of policy. That's the kind of thing you uncover when you actually look at how regulations are implemented.

Finally, regarding funding, yes, NIH spends about $31B per year, which is a lot. However, drug companies spend $4B per drug approved[1], which is an incredible amount of money when multiplied across all drugs. I'm not sure exactly how one could stop drug companies from profiting from public domain research as you propose. Are you saying that NIH should get into the business of drug development and/or not allow its funded academics to publish papers or start drug companies?

If you are saying the former, I actually happen to agree that NIH would be reasonably good at drug development, as Francis Collins has proposed, because as a fellow .gov it would be able to play hardball with the FDA in a way that no normal company could. Among other things, it wouldn't fear going out of business, and would be able to appeal to the HHS secretary if FDA retaliated against it. On the other hand, this new NIH-to-FDA pipeline would lose a lot of checks and balances; it'd sort of be like HHS as the large drug co with NIH as the scientists and FDA as the regulatory affairs, without any real check by the market other than the nationalized drug companies of other countries.

Think about how the FDA fast tracked [2] things like TSA body scanners and you'll get a sense for what its actual commitment to safety is when it's a fellow .gov that is sponsoring a drug/device.

As a final point, if you meant instead that NIH should be abolished and academics should stop publishing papers, I think we will actually see the implosion of the US higher ed research establishment over the next 5-10 years due to MOOCs and budget cuts, so that may come to pass as well.

[1] http://www.forbes.com/sites/matthewherper/2012/02/10/the-tru...

[2] http://arstechnica.com/science/2010/11/fda-sidesteps-safety-...

So, a few points (I didn't downvote you).

1) First, FDA fast-tracks many bad things. Hundreds of millions of people were irradiated by scanners that FDA waved on through because a fellow .gov agency (TSA) sponsored them. So: even the risk-averse can't trust a single centralized regulator to be "risk-averse" rather than "pro-government". We need multiple regulators (see my posts elsewhere in the thread), where you can use things approved by the slower/expensive/safest one while I can use items approved by the faster/cheaper/riskier ones.

http://arstechnica.com/science/2010/11/fda-sidesteps-safety-...

  Dr. Holdren passed the letter on to the Food and Drug 
  Administration for review. But, in the FDA's response, the 
  agency gave the issues little more than a data-driven brush 
  off. They cite five studies in response to the professors' 
  request for independent verification of the safety of these 
  X-rays; however, three are more than a decade old, and none 
  of them deal specifically with the low-energy X-rays the 
  professors are concerned about. The letter also doesn't 
  mention the FDA's own classification of X-rays as 
  carcinogens in 2005.

2) Second, the formal IND fast-track program you mention is very political to get into (on the device side there's something similar called Pathway to Innovation). Moreover, FDA doesn't count days like you and I count days. It's like an NFL game which is 60 minutes but actually takes three hours; every time they email you back, it stops their clock. And they can email you back to ask for data that takes months to gather. This is from a device consultant but the principle is the same for drugs:

http://www.myraqa.com/blog/how_long_is_90_days

  By law, FDA must respond to your 510(k) within 90 days, and 
  typically they do. The thing you have to understand is that 
  FDA measures 90 days about the same way the NFL measures 
  the 60 minutes in a football game. It's not unusual for the 
  clock to spend more time stopped than running.

3) Third, regarding thalidomide, as you probably know there were three major catastrophes that increased FDA power (1906 publication of the Jungle which birthed proto-FDA, 1938 elixir of sulfalinamide, and 1962 thalidomide) and another major catastrophe in the early 90s that reduced FDA power (FDA delays on AZT and slowdown of AIDS drugs).

Thalidomide in particular is to the FDA what 9/11 is to the TSA, it's the justification for everything they do. If you get into the history books you'll see that Frances Kelsey never actually suspected teratogenic effects; she suspected neurological issues. Moreover, thalidomide was actually a very efficacious drug for morning sickness, it was just unsafe. Yet the 1962 revision to the FD&C act added efficacy testing on top of safety testing.

That's weird. The thing is, toxicological/safety testing, even aggressive safety testing is "only" in the tens of millions, not billions. It's efficacy testing (and then comparative effectiveness) that really piles on the dollars. If the lesson of thalidomide was that we should do aggressive safety testing, then no one got the message, because Kefauver & Harris' 1962 amendments to FD&C meant we ended up spending several hundred billion dollars on efficacy instead.

Perhaps then the lesson from thalidomide might be that pregnant mothers should be much more risk-averse in what drugs they take. It's not really a lesson that says "we need to delay all drugs more", because due to pharmacogenomics some side effects are only going to be apparent when you introduce them into humans on a large scale anyway.

Moreover, risk can't be eliminated, and different people will have different risk profiles. What if a 70 year old man with terminal cancer wants to take an experimental, non-FDA approved drug? Do you sue like the FDA did in Cowan vs. US to prevent him from doing so?

For that matter, what if a 25 year old pregnant woman wants to take a new drug? Do we prevent her from doing so? Maybe we should, but we currently don't stop pregnant women from drinking alcohol or smoking cigarettes.

One has to think very carefully about whether every tragedy means one must ban or mandate something with a federal law.

For money, obviously.