Posted 16 March 2016
By Zachary Brennan
Two Harvard professors are taking issue with the recent landmark court decision allowing some "truthful and non-misleading" off-label pharmaceutical marketing in a new paper, saying “informativeness in asserting scientific facts, rather than truthfulness, ought to be the gold standard for evaluating commercial speech about pharmaceuticals.”
The US Food and Drug Administration (FDA) generally does not allow pharmaceutical companies to promote drugs for unapproved (i.e., off-label) indications.
Along comes the small Ireland-headquartered Amarin Corp., which developed the FDA-approved fish oil drug Vascepa (icosapent ethyl) to treat “very high” levels of triglycerides. However, the company wanted to market the product to physicians for patients with moderate triglyceride levels, as well (≥200 mg/dL and <500 mg/dL) to reduce those patients’ risk of cardiovascular disease.
While the drug was still in development in 2009, the company made a deal with FDA under which the agency would approve Vascepa as a treatment of moderately high triglyceride levels provided that Amarin completed a clinical trial demonstrating that Vascepa reduced persistently high triglyceride levels among statin-treated patients.
But while this study was underway, other clinical trials involving the non-statin cholesterol-lowering drugs niacin and fenofibrates failed to show that reduction in lipid levels with these drugs correlated with a reduction in cardiovascular disease.
FDA used these results to nullify its commitment to approve Vascepa, which, as the authors point out in PLOS Medicine, is “an action which [FDA] has only taken ten times in approximately 1,000 such agreements over the past 7 years.”
Amarin ended up suing FDA in May 2015 over its right to distribute off-label statements on this unapproved indication under the First Amendment, asserting that because the statements were “truthful and non-misleading,” it has the right to make them to doctors. In August 2015, a federal court agreed with Amarin and a little more than a week ago, the two sides settled the case.
At issue for the professors, Spencer Phillips Hey and Aaron Kesselheim, both of whom work for the Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, is the fact that the off-label promotional statements from Amarin are not actually truthful because they are not informative about the current state of scientific evidence.
To illustrate that Amarin’s argument is “faulty, because the so-called ‘truthful and non-misleading’ statement is a tautology,” the authors slightly alter the language of the Amarin statements distributed to doctors: “Supportive but not conclusive research shows that consumption of EPA [acid eicosapentaenoic acid] and DHA [docosahexaenoic acid] omega-3 fatty acids may ormay not [bold is theirs] reduce the risk of coronary heart disease.”
“All this qualification really ‘says’ is that non-conclusive research has been conducted, but then the second half of the claim expresses nothing at all about the clinical import of that research,” the authors say.
Amarin’s successful lawsuit provides it with the ability “to make truthfully-ambiguous claims when marketing its prescription drug products is troubling,” the authors concluded. “There can certainly be disagreement over the state of evidence and the warrant of inferences. But this does not mean that anything goes. The FDA rescinded its agreement with Amarin because of a qualitative shift in the accumulating state of scientific evidence, transforming what would have been a valid scientific claim into an invalid one. This is unfortunate for Amarin, but uncertainty about how evidence will evolve is an intrinsic feature of the scientific enterprise. The truth must evolve accordingly.”
An Uninformative Truth: The Logic of Amarin’s Off-Label Promotion