August was a rough month for the Food and Drug Administration. On August 7, a federal judge in New York entered a preliminary injunction in Amarin Pharma, Inc.’s lawsuit against the FDA, holding that the FDA could not prevent a drug manufacturer from marketing its drug for uses that haven’t been approved by the FDA, so long as the marketing was “truthful,” a loaded word we’ll get to in a moment. Then, on August 20, Forbes published an analysis that concluded the FDA approves 96% of new drugs or; in essence, “the FDA is basically approving everything.”
Let’s start first with the Amarin lawsuit. The primary weapon in the FDA’s legal arsenal is the “misbranding” statute, which allows the FDA to prosecute anyone who markets a drug or medical device “if its labeling is false or misleading in any particular.” For decades, the FDA has attempted to keep pharmaceutical companies in line by telling them that, if they market a drug for uses that were not approved by the FDA, so-called “off-label marketing,” the FDA will prosecute them. However, the pharmaceutical industry, emboldened by Citizens United, has tried to make this into a free speech issue in recent years.
On the one hand, the pharmaceutical companies have a point: why shouldn’t drug companies be allowed to “truthfully” market their drugs?
On the other hand, this argument about the “truth” falls apart when we consider the complexity of drug efficacy and safety, and when we recognize the billions of dollars that drug companies will use to push their “truth” on unwitting doctors and patients.
Amarin makes a prescription drug called “Vascepa,” which is essentially an expensive version of fish oil. The FDA approved Vascepa for use in patients with severe hypertriglyceridemia based on the results of a single clinical trial. The FDA did not, however, approve Vascepa’s use in patients with very high triglycerides for the rather straight-forward reason that it doesn’t work. Read for yourself the FDA’s 94-page Advisory Committee Brief. Vascepa lowers triglyceride levels, but it hasn’t been shown to actually reduce the risk of cardiovascular disease. This isn’t some sort of attack on Amarin or Vascepa particularly; medical science as a whole has come to realize that, apart from severe hypertriglyceridemia, omega-3 supplementation doesn’t do anything to reduce patients’ risk of “all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke.” As a matter of medicine, unless a person has truly severe hypertriglyceridemia, omega-3 supplementation isn’t going to make much of a difference.
From the FDA’s standpoint, this was a no-brainer: Amarin failed to show that Vascepa was effective. I doubt anyone at the FDA figured they would lose in court over this one.
That said, for all the noise that has been made in the press about the Amarin ruling, it wasn’t a complete victory for the company. Although the court’s injunction allows Amarin to amend the Vascepa label to include information about the lowering of triglyceride levels, the court also held the FDA could force Amarin to include on the Vascepa this disclaimer:
Vascepa is not FDA-approved for the treatment of statin-treated patients with mixed dyslipidemia and high (≥ 200 mg/dL and < 500 mg/dL) triglyceride levels due to current uncertainty regarding the benefit, if any, of drug-induced changes in lipid/lipoprotein parameters beyond statin lowered low-density lipoprotein cholesterol on cardiovascular risk among statin-treated patients with residually high triglycerides. No prospective study has been conducted to test and support what, if any, benefit exists.
Slip op. at 60.
That’s better than nothing, but at its core there’s a huge problem: judges aren’t experts on science, medicine, or statistics. How, exactly, did the court reach the factual finding that there is “current uncertainty” about omega-3 supplementation on cardiovascular risk? As the FDA’s Advisory Committee Brief showed:
Since 2007, multiple interventional cardiovascular outcome trials in patients receiving omega-3 [fatty acids] have been published with varying effect on the primary cardiovascular endpoint. In recent years, the majority have reported negligible impacts on cardiovascular events.
Within the last two years, two large, randomized, placebo-controlled cardiovascular outcome trials have failed to demonstrate an effect of supplementation with omega-3 [fatty acids] on the risk for cardiovascular events.
In addition to these trials, several meta-analyses of clinical trials of omega-3 [fatty acids] and cardiovascular events have been published recently. The majority have failed to confirm cardiovascular benefit from EPA and DHA supplementation, but despite large overlap in the studies reviewed, one meta-analysis did suggest possible cardiovascular benefit.
The scientific consensus is that omega-3 supplementation — and thus use of drugs like Vascepa — either do nothing at all or might provide “negligible impacts” and “possible” benefit.
To me, the Amarin case is another unfortunate example of a problem I decried over at TortsProf two years ago: the rise of judicial omniscience. However gifted a judge may be — and the Amarin opinion is certainly the work of a gifted judge — judges simply aren’t in the position to decide these types of issues, and our court system isn’t set up to make judges the final arbitrators of scientific issues.
When it comes to something this complicated and fact-specific, we really only have two options. Either we trust the FDA to do its job appropriately when approving drugs — and based on the Forbes article it seems the FDA is, if anything, extremely liberal when it comes to those approvals — or we leave it to juries to sort out these questions. The latter would seem the most appropriate course under our existing case law, given the Supreme Court’s recognition in Wyeth v. Levine that “because the [misbranding] statute contemplates that federal juries will resolve most misbranding claims, the FDA’s belief that a drug is misbranded is not conclusive.”
At first blush, it seems odd to trust to a jury a scientific determination that we wouldn’t trust to a judge, but that’s not the point. The problem with the Amarin decision is that the court went beyond merely deciding if the label Amarin wanted to use was false — which is all that the jury in a misbranding prosecution would decide — and instead tried to fashion a remedy by diving into the deeper substance of what should, and should not, be on the label. That took the court too far from the field of law and too deep into the substance of science. There’s a role for judges in every case; the problem comes when the judge acts as judge and jury.
We don’t have just a First Amendment, we have Sixth and Seventh Amendments, too, both of which reinforce the primacy of the jury in resolving disputed facts in our legal system. The checks and balances on the FDA’s misbranding statute aren’t to be found wearing robes, they’re to be found in the jury box.