Off-Label Promotion: The Game Is UpOff-Label Promotion: The Game Is Up

FROM THE EDITORS

When it comes to off-label promotion, FDA and industry have been engaged in a cat-and-mouse game for years. And in March, Congress got involved, too.

The House Committee on Oversight and Government Reform wrote to Johnson & Johnson and Boston Scientific to announce an investigation into the marketing of drug-eluting stents. Committee chairman Henry Waxman (D–CA) was inspired by the December hearings on drug-eluting stent safety, in which it was revealed that the products are used off-label about 60% of the time. If the percentage of off-label use is so high, Waxman deduced, then perhaps the manufacturers are doing something improper to encourage it. The firms announced they would comply with the investigation.

Just days later, CDRH officials met with manufacturers of coronary and bile-duct stents to remind them about guidelines against off-label promotion. In particular, the agency warned against promoting bile-duct stents for coronary applications, and it admonished some firms for advertising them at a cardiology meeting. According to one published report, 90% of bile-duct stent sales are to catheterization labs, where presumably they are used primarily for vascular applications. Again, by deductive reasoning, authorities must figure that if that number is so high, there must be some off-label promotion going on. It gave bile-duct stent manufacturers three weeks to change their marketing tactics.

“People had known for a long time that a lot of stents are used off-label,” says attorney Robert J. Klepinski of Fredrickson & Byron (Minneapolis). “This news is not a surprise, but I wasn't expecting it to happen right now.” Klepinski is an expert on promotion and marketing of devices.

This sort of give-and-take has gone on for years. Device manufacturers are not allowed to promote off-label uses directly. But the federal courts have held that some forms of indirect off-label promotion, such as certain kinds of references to independent studies of off-label uses, are allowed. FDA is not allowed to regulate the practice of medicine. It has no control over what doctors do, but it does have control over what manufacturers do. Therefore, FDA leans on manufacturers to try to prevent unapproved use of devices.

“FDA is not allowed to go down that road [of regulating the practice of medicine], but it has been gradually working that angle for a long time,” says Klepinski.

What's resulted is a situation in which FDA is trying to get around its prohibition on influencing the practice of medicine, and industry is trying to get around its prohibition on off-label promotion.

Klepinski believes that firms resort to off-label promotion because “the premarket approval bar is set so high” and because doing clinical trials for new indications can be prohibitively expensive. Yet, he says, FDA doesn't allow real-world off-label experience to be considered when deciding whether to approve a new indication. That makes getting a new indication approved burdensome and may tacitly encourage firms to try to flout the promotion rules instead. “So FDA traps itself in a vicious cycle. What we need is a less shortsighted approval process. Sometimes FDA's pursuit of so-called good science lags behind the real science of treating patients.”

It's time to bring the issues into the open. Step up surveillance of any safety problems related to off-label use. But acknowledge that it does happen and allow the real-world data to be used more freely. That acknowledgment could create a more streamlined, less burdensome process for new indication applications, and it could cut down on unsafe use of devices. The current system encourages, albeit unintentionally, breaking the rules, at a potential cost to patient safety. It's time to encourage companies to follow them.

Erik Swain for the Editors