The FDA is considering letting pharmaceutical companies give information to doctors and insurance companies on prescription off-label drugs.
This practice, usually referred to as “off-label promotion or marketing,” has been prohibited since 1962, when Congress passed a law requiring drug companies to establish, through rigorous testing and clinical trials, a drug’s safety and effectiveness for each intended use.
The FDA held a public hearing on off-label promotion on November 9 and 10, 2016. Some 50 people testified, including drug company representatives, academics, insurance company executives, doctors, public health experts and consumer advocates.
Occurring the day after the election, the mood was somber amid Donald Trump’s surprise win. Because almost all the speakers read from prepared statements, few addressed the question that hung over the meeting: What now, under Trump, for the FDA and drug regulation?
Trump’s transition website lists FDA reform as a healthcare priority, but there are no details. He campaigned on an anti-regulation platform. In recent days, media outlets have reported that FDA leadership would be replaced. The thinking among many at the hearing was that a Trump administration would look favorably on loosening rules for drug companies.
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Will There Be an Easing of Off-label Regulations?
That’s certainly the drift of things legally, which is what prompted the hearing. In 2014 and 2015, the U.S. Supreme Court, in 2 decisions, strengthened First Amendment protection for companies. That is, the Court extended their “free speech” rights, equating those rights to those of citizens’ in a way that had not been done before.
The pharmaceutical industry has interpreted the decision as giving them more leeway to communicate to doctors, hospitals and insurers more openly about their products. Indeed, the industry has won several court cases that have weakened the FDA’s authority to regulate off-label marketing.
In 2 cases, courts found that drug company off-label marketing materials for off-label uses were “truthful and non-misleading.” And in March, the FDA settled with one company, Amarin Pharmaceuticals, which had sued the FDA to gain the right to push its fish-oil drug Vascepa for unapproved uses. The company got what it wanted in the settlement. As part of the deal, it dropped its First Amendment lawsuit.
That settlement was widely seen as setting a precedent that could open the gates for similar requests from other companies, even though the larger legal issue of whether the FDA’s restrictions on off-label marketing are unconstitutional remains unresolved.
Predictably, drug and biotech company executives testified in support of more FDA flexibility on off-label promotion. But most company-affiliated speakers acknowledged the risks involved in opening the gates too widely or too rapidly.
Michael Labson, a lawyer who testified on behalf of the Pharmaceutical Research and Manufacturers of America (PhRMA), said the FDA should establish “safe harbors” for communicating certain types of information outside a drug’s approved labeling with doctors and payers.
But Labson also urged the FDA to adopt rules that would allow drug companies to use “real world evidence” — such as from studies of doctors’ results using a drug off-label — on “medically accepted unapproved uses” to promote products.
The Opposing View
FDA Deputy Commissioner Rachel Sherman suggested that was overreaching and consumer advocacy groups were adamantly opposed. Sherman asked: “What is a ‘medically accepted unapproved use’ that should be communicated versus one that might not be?”
Sidney Wolfe, a doctor and founder of Public Citizen’s Health Research Group, as well as a long-time FDA critic, was assertive: “The FDA would be reckless to weaken rules and allow the pharmaceutical and medical device industry to promote products… not proven to be safe and effective,” Wolfe said. “Opening the door to the promotion of potentially dangerous products undermines the entire FDA approval process. The FDA needs to slam this door shut.”
Wolfe cited research indicating that 80% of off-label prescription drug use lacks any or sufficient evidence of effectiveness, and is associated with a more than 50% increase in side effects compared to on-label uses.
Doris Peter, testifying on behalf of Consumer Reports and its prescription drug education initiative Consumer Reports Best Buy Drugs, also spoke in opposition. She said findings from a recent survey of 1,000 consumers indicate that “Americans do not want the FDA to allow the pharmaceutical industry to promote off-label uses of medications….The FDA will abandon its mission if it allows off-label promotion,” Peter testified.
The Consumer Reports survey found that 78% of respondents said it was either extremely or very important to them that the FDA fully vet the safety and effectiveness of medications for any specific use. And 84% opposed advertising of medicines for unapproved uses.
The Danger
Somewhere between 12% and 20% of all prescriptions are for off-label uses. Doctors are permitted to prescribe any approved drug off-label because there’s no law or regulation prohibiting it.
The reasons for that are complex, but basically doctors’ trade organizations (like the American Medical Association) didn’t want the FDA — or anyone — to be able to dictate the practice of medicine. Congress went along with that. Regulate the approval of drugs, yes. Tell doctors what to do, no.
The core problem with opening the gates to drug company off-label promotion — as opposed to physician prescribing — is that companies would have even more financial incentive to do it. And that incentive is already powerful, as I pointed out in a recent MedShadow blog.
Two numbers tell the story. Over the past 25 years, the federal government has collected around $15 billion in civil and criminal fines from pharmaceutical companies for off-label promotion. But experts estimate that sales of the drugs involved in those cases yielded pre-tax profits that are at least 10 times that amount — $150 billion.
Advice
Doctors and research agree that some off-label uses are warranted. Cancer drugs are routinely prescribed off-label, for example, with acceptance. But bear in mind, as mentioned above, that the vast majority of off-label use is not well grounded in science or backed by strong evidence.
In addition, it’s usually much riskier because off-label uses are less studied. In a study published in January, the rate of side effects was 54% higher for off-label uses than on-label uses.
Most doctors know when they are prescribing off-label, but they don’t always tell patients. Neither do pharmacists. So, you have to ask, and always should with every new prescription, especially if the drug is being prescribed in an inherently risky or high-stakes situation, such as cancer treatment.
Make it routine practice as well to check every drug you take online. The approved indications are easy to find. Try the DailyMed website run by the National Institutes of Health. Search by drug, then click Indications & Usage.
What takes more digging is finding out if an off-label use is widely accepted and backed by good evidence. Web sites like drugs.com and WebMD often don’t have information about off-label use. You have to Google it. And, of course, circle back to your doctor if you don’t find the information you need.
If you are prescribed an expensive drug off-label, you are likely to hear about it from your pharmacist or health insurer. It may not be covered. That’s another reason to be proactive in getting the information up-front from your doctor.
