What Was The FDA's Statutory Authority For Granting Marketing Exclusivity On Colchicine?

Maybe this seems obscure, but it gets to the heart of something I've wondered about for quite some time: how did URL Pharma get a licensing exclusivity on colchicine? Colchicine is a drug made from the autumn crocus, Colchicum autumnale, and has been known since antiquity as a curative for gouty arthritis. From Wikipedia:

An unintended consequence of the 2006 U.S. Food and Drug Administration (FDA) safety program called the Unapproved Drugs Initiative — through which the FDA sought more rigorous testing of efficacy and safety of colchicine and other unapproved drugs^[27] — was a price increase of 2000 percent ^[28] for "a gout remedy so old that the ancient Greeks knew about its effects."^[28] Under Unapproved Drugs Initiative small companies like URL Pharma — Philadelphia drugmaker — were rewarded with licenses for testing of medicines like colchicine. In 2009, the FDA reviewed a New Drug Application for colchicine submitted by URL Pharma. URL Pharma did the testing, gained FDA formal approval and was granted rights over colchicine. With this monopoly pricing power, the price of colchicine increased.

In 2012 Asia’s biggest drugmaker — Takeda Pharmaceutical Co. — acquired URL Pharma for $800 million including the rights to colchicine (brand name Colcrys) earning $1.2 billion in revenue by raising the price even more.^[28]

Oral colchicine had been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings.^[29] On July 30, 2009 the FDA approved colchicine as a monotherapy for the treatment of three different indications (familial Mediterranean fever, acute gout flares, and for the prophylaxis of gout flares^[29]), and gave URL Pharma a three-year marketing exclusivity agreement^[30] in exchange for URL Pharma doing 17 new studies and investing $100 million into the product, of which $45 million went to the FDA for the application fee. URL Pharma raised the price from $0.09 per tablet to $4.85, and the FDA removed the older unapproved colchicine from the market in October 2010, both in oral and intravenous forms, but gave pharmacies the opportunity to buy up the older unapproved colchicine.^[31] Colchicine in combination with probenecid has been FDA-approved prior to 1982.^[30]

In August 2009, colchicine won FDA approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever.^[32][33] It had previously been approved as an ingredient in an FDA-approved combination product for gout. The approval was based on a study in which two doses (1.2 mg and 0.6 mg) an hour apart were as effective as higher doses in combating the acute flare of gout.^[11]

 The Unapproved Drugs Initiative page is singularly unhelpful when attempting to decipher where the FDA thought they were entitled to take this action, but the FDA's page on the colchicine enforcement action is, particularly citing Familial Mediterranean Fever as an excuse the justification for attaching "orphan drug" status to it (21 U.S.C. 360bb). This allowed URL Pharma to get marketing exclusivity for the drug, and all the rest. It's not clear that the Wikipedia page entry's blaming of Hatch-Waxman is appropriate.

Credit to @molratty on Twitter for background assistance.

Justice As An Explicit Roll Of The Dice: How Many Men Are Rapists?

One of the things we heard constantly during the Brett Kavanaugh confirmation hearings was the old saw that false reports of rape amount to "2 to 8%". Some while back, Scott Greenfield some while ago published a fine review of the statistics of false reports, which found a disparity in terminology that left us with this:

True-ish: 35.3%
Definitively False: 5.9%
Inconclusive: 58.8%

But the thing I wanted to look at was the reverse of the "2 to 8%" figure (actually, 2-10% per Greenfield). If we're supposed to "believe" accusers on the basis of a low reported false accusation rate, why isn't it equally valid to decide guilt based on the number of genuinely innocent men? That is, shouldn't also "believe" men who claim innocence, on exactly the same evidentiary grounds? But how innocent? Let's try to figure out the percentage of the male population that are rapists. We start with Uniform Crime Report data. This counts reported rapes since 1960; the data tool provides data to 2014. So, using the "Legacy Rape" data*,

• Sum the number of reported rapes from 1960-2014: 4,002,079
• Divide by the 2014 population (318,857,056): 1.26%
• Multiply by 2 (because men are half the population):  2.51%
• Adjust for the RAINN estimated 69% non-reporting rate: 3.64%

The above assumes a 1:1 ratio of rapes to rapists, which contradicts the repeat offender theory of David Lisak and others. It also assumes that the number of rapists is not in part diminishing, because the oldest rapes in that count includes some that might have been committed by men now dead. This is important, because it artificially raises the male rapist percentage. Nonetheless, if we were to say that the number of false rape reports is a reason to "believe" the accusers, the even smaller percentage of male rapists in the general male population (versus the high end of false accusers at 8% or 10%) is an even stronger reason to acquit.

Of course, both of these are stupid; we don't roll the dice to determine guilt or innocence, but look at the individual circumstances of the charges and the presented evidence. N.b., I also didn't investigate actual convictions, because the Bureau of Justice Statistics website is presently broken.

---

*"Legacy rape" corresponds well to men raping women; the "Revised Rape" tallies include "penetration, no matter how slight, of the vagina or anus with any body part or object, or oral penetration by a sex organ of another person, without the consent of the victim", which would obviously include prison rape.