-- Louis Gottlieb/1961
That likely describes the situation FDA petty bureaucrats find themselves in today. On the one hand, one of its earliest heroes passed away. On the other, Amarin won its lawsuit. Quaking galore.
Frances Kelsey didn't believe the manufacturer of thalidomide:
"I had the feeling," she wrote after a meeting with company executives, "that they were at no time being wholly frank with me, and that this attitude has obtained in all our conferences, etc., regarding this drug."
Merrell's data wasn't enough to convince her. What's odd is that the thalidomide fiasco is credited with the FDA's emerging efficacy persnicketyness that continues to this day. But the issue with thalidomide wasn't efficacy. In actually did its job quite well, which is why it was widely prescribed in Europe. FDA, from the beginning, had drug safety as its primary remit. It was safety that Kelsey focused on; age old FDA business.
... attention focused on her partly because the Kennedy administration and its allies in Congress wanted to use the case to pass stronger drug regulations. The 1962 law required tighter proof of the safety and effectiveness of new drugs, full disclosure of side effects and generic names, and swift removal of unsafe drugs from the market.
Which brings us to the quaking. It's rather a long and torturous story, but the short version is that Amarin developed a highly purified fish oil, that was shown to lower LDL substantially. The FDA approval was for those with sky-high LDL, which is a small market. Amarin want to expand the label to include more moderate, but still high, LDL; a much larger market. Along the way FDA had said, "leap this hurdle, and you get the expansion". Amarin did so. Then FDA decided that lowering LDL wasn't a meaningful measure of a drug's effectiveness vis-a-vis heart attacks and such, so Amarin wouldn't get its expanded label. Amarin sued, on the basis that it had the First Amendment right to promote the drug with its data.
The preliminary ruling in U.S. District Court could strengthen the pharmaceutical industry's ability to distribute information about drug uses that have not been cleared by the FDA. That issue has been contested for years by the FDA and the companies it regulates.
Hmmm?? See why the quaking?
Now, it has been true for decades, if not forever, that doctors can prescribe FDA approved drugs for use not on the label, "off label" use as they say. But manufacturers and such aren't allowed to promote, advertise, or claim use not on the label. Amarin now has, modulo successful appeal by FDA, the right to actively sell its drug to anyone with high LDL. The ruling sets precedent, certainly not yet tested, for all drug companies to promote any use for which there is "truthful" data. For those who follow drug approvals, drug companies don't always play fair with trials. In particular, they have the habit of cherry-picking sub-groups from failed trials which show stat sig numbers. Strictly speaking, such stat sig results aren't "truthful" because the trial design, in most cases, isn't powered to support such a posteriori sub-groups. Just to be clear, Amarin didn't apply to expand using such tactics. It ran a trial approved by FDA, and met the endpoints. Basically, FDA changed its mind after the fact. Kind of the same sort of sleight of hand used by drug companies.
This will definitely get interesting.
To further the murk, thalidomide is usefully prescribed today for leprosy and cancer.
In the 2000s, the combination of thalidomide and dexamethasone, often in combination with melphalan, became one of the most common regimens for patients with newly diagnosed multiple myeloma.