Legal expert explains WLF decision

On July 28, a district court judge in Washington ruled that some provisions of the FDA Modernization Act are unconstitutional because they violate pharmaceutical companies' rights to free speech. Judge Royce Lamberth's controversial decision, which will affect the FDA's ability to control the dissemination of off-label uses information, is a landmark that has legal experts, the FDA and the pharmaceutical industry abuzz with speculation: How will the FDA proceed from here? Will pharmaceutical sales reps incorporate off-label uses into their product details? And if pharmaceutical companies can promote products to physicians for unapproved indications, will they bother to go through the FDA's formal, time-consuming and costly approval process?

Sandra J.P. Dennis, a partner at Morgan, Lewis & Bockius spoke with Pharmaceutical Representative about the WLF vs. Henney case, its meaning and its possible implications for the industry and the FDA.

PR: What does the WLF case mean for the pharmaceutical industry?

Dennis: The WLF case means that pharmaceutical and medical device companies can have more flexibility and opportunity to disseminate the results of research on approved drugs and devices. If the [research results] are published in bona fide peer-reviewed journals or textbooks, even if they discuss off-label uses, the WLF decision allows the dissemination of those materials.

Prior to this, there were far more limitations on what could be disseminated. For example, the FDAMA provisions would have permitted the dissemination of such materials only if the sponsor was seeking approval of the uses, which meant they could have a supplemental application filed or they could certify that they were going to apply for supplemental indication. The most significant result of the recent decision is that companies may disseminate peer-reviewed off-label information without seeking a supplemental approval.

Now, if companies are savvy, they are going to put more effort into supporting clinical research of off-label uses and to having those results published in peer-reviewed journals. That's the opportunity for companies. They can encourage research on off-label uses in a form where the results can be disseminated.

PR: Where does this leave the FDA?

Dennis: Significantly, it means the FDA's power to limit information distributed by pharmaceutical companies is not absolute. FDA has extensive authority but FDA may have projected that authority to be all encompassing. The court, in the WLF case, did not agree with that.

The court's decision demonstrates that companies can disseminate off-label scientific information. The FDA is not prohibited in regulating that information somewhat, but FDA cannot regulate it excessively.

PR: Why was the FDA able to restrict off-label uses information for so long?

Dennis: The guidances in FDAMA weren't issued until 1996 and 1997, and they were challenged right away. It's not a case of years and years of misleading the industry. Prior to FDAMA, the FDA based its internal policy on whether or not the information was false or misleading but began, over the years, to take the position that any information that was not FDA-approved was inherently false and misleading. The court vehemently disagreed with this. There's a great quote from [Lamberth's 1998 ruling]: "FDA exaggerates its overall place in the universe by asserting that any and all scientific claims…regarding prescription drugs are presumptively false and misleading until the FDA has had a chance to review them."

PR: Why did the FDA argue that it had a right to regulate it in the first place?

Dennis: The FDA argued that the dissemination of the information was conduct, not speech. But, in its 1998 decision, the court looked at this information as speech, and speech is protected by the First Amendment. Then, the court looked at whether it is commercial speech, which is less protected than other speech. It is protected, but there is a valid government interest in restricting that information. The court decided that it is commercial speech.

Once the court decided it was commercial speech, it ultimately found that the valid government interest here is having companies gain FDA approval of off-label uses. That's the reason why FDA presumably would seek to limit the information. If companies can distribute information unfettered, they might never seek approval for any additional use. Therefore, there is a valid public health reason and a valid reason for FDA to encourage companies to obtain supplemental approval. However, the restrictions that FDA imposed were found by the court to be excessive, more excessive than would be necessary to protect that government interest.

PR: So, what can the FDA regulate about off-label uses and what can't it regulate?

Dennis: The journal articles that are distributed must be in peer-reviewed publications; the text books must be reference textbooks published by a bona fide independent publisher; CME seminars, if sponsored by a company, must be monitored by an independent provider that is accredited; that FDA can still - and this is a primary part of the statute - prohibit the dissemination of any information that is false or misleading. And that FDA can require companies to disclose any financial interest (support for seminar or article) and disclose the fact that the use has not been approved by the FDA. Those limits are viewed by the court as reasonable. Other [limits] were determined to be overly restrictive.

PR: Does this mean pharmaceutical sales reps can talk to physicians about off-label indications?

Dennis: Not exactly. The case really only permits the dissemination of scientific, peer-reviewed articles. A sales rep's discussion is not peer-reviewed. While the sales rep can hand out the article and say to the doctor, "Here's an article talking about research on our drug in this particular area," it's still not permissible for the sales rep to engage in a substantive discussion. If the doctor has questions, the sales rep should direct the doctor to the medical department of the company.

PR: Will pharmaceutical companies bother to go through the formal, time-consuming process of getting products FDA-approved for new uses if they can disseminate off-label information?

Dennis: There are definitely instances where the companies will find it doesn't make sense to go through the supplemental indication process because they can disseminate information without it. There are advantages to taking this route, but there are also limitations. It's a stretch to call disseminating articles "promotion," in the full sense of how a company might want to promote a product. Without the supplemental indication, they can't use direct-to-consumer advertising, they can't advertise in medical journals, they can't distribute brochures or handouts, they can't have sales aids and sales people can't engage in discussion.

Companies will have to decide if it's worth it on a case-by-case basis. It will depend on the type of drug, the therapeutic area, the competition and the marketplace factors. PR