Keep Limits On Off-Label Promotion, Consumers And Patients Say

Prescribers can get information they need through continuing education programs and scientific conferences, non-industry stakeholders tell US FDA during second day of meeting on manufacturer communications for unapproved uses.

Continuing medical education, professional meetings and scientific conferences are adequate mechanisms by which drug manufacturers can share data about unapproved uses, consumer advocates and academic researchers said Nov. 10 in arguing against any relaxation of FDA restrictions on off-label communications.

During the second day of a two-day FDA hearing, agency officials listened to more than two dozen individuals, the majority of whom suggested that allowing more communications about off-label use would increase prescribing for uses that have not been proven to be effective or safe, potentially leading to devastating adverse events.

Consumer and patient advocates said allowing more communication about off-label data would increase prescribing for uses that have not been proven safe or effective, potentially leading to devastating adverse events.

Although some patient advocates said they favored allowing a greater flow of information between manufacturers and prescribers, many talked of injuries to themselves or loved ones, and the deaths of family members, following off-label use of prescribed drugs.

"Promotion by manufacturers of off-label uses to medical professionals upsets the balance of informed medical decision-making," said Margaret McCarthy, executive director of the Collaboration for Research Integrity and Transparency at Yale University. "We support the agency's longstanding authority to regulate such communications and recommend that any changes that the agency implements will strengthen and not weaken its regulations."

The comments were in stark contrast to the input FDA received on the meeting's first day, when biopharmaceutical and medical device industry representatives said the agency must modernize its regulatory regime to align with First Amendment case law and enable better-informed decision-making by health care providers, patients and payers. (Also see "Off-Label Communications: Industry, FDA Debate Role Of Peer Review" - Pink Sheet, 9 Nov, 2016.)

Communication Mechanisms Already Exist

FDA officials asked speakers how study results about off-label uses should be communicated if the current limitations on manufacturer communications about unapproved uses of approved products are not changed.

FDA Senior Policy Advisor Kristin Davis noted that medical product industry representatives have asserted a more effective way to communicate about data regarding unapproved uses is needed because health care providers cannot wade through all the available published literature on such uses.

"Do you have any thoughts about if there is robust data for an off-label use, whether there is a communication mechanism for providers that you would support to make them aware of that outside of the literature," Davis asked McCarthy.

"I think that there already are mechanisms in place for that," McCarthy said. "I think a good example is practice parameters that are evidence-based. … Medical societies produce those already, and those are based on careful review of the literature and also experience gained from practice."

"I think that the difficulty is that if there were direct marketing allowed, more than is already allowed by the pharmaceutical companies directly to physicians and other prescribers … many prescribers simply lack the time to accurately assess it," McCarthy said.

Particularly in the primary care setting, providers "may not have access to these journals. They don't typically have a subscription," McCarthy said. "I think that professional associations, conferences, are a more appropriate way to convey that information."

CME Programs A 'Well-Oiled Machine'

Lisa Gill, deputy content editor for Consumer Reports' Best Buy Drugs, highlighted the prolific use of continuing education programs to discuss data on off-label uses.

Before joining Consumer Reports, Gill held a job that involved in ghost-writing and editing continuing medical education (CME) programs for doctors and continuing education for pharmacists. She also developed educational grant requests submitted to pharmaceutical companies.

"I can assure you that the mechanism for off-label communications between drug companies and prescribers already exists," Gill said. "It's a well-oiled machine, and for a time I was part of that machine."

She drew a contrast between her experience and the statements made by medical product industry representatives a day earlier.

"We heard half a day's worth of industry testimony yesterday where it sounded very dire, it sounded as though doctors were unaware of potential off-label uses and they weren't getting the important information that they needed," Gill said. "That continuing medical education mechanism is in place. It's been in place for a really long time. …That is a sort of safe harbor communication that exists and it's there."

"I find it sort of irresponsible to come up and try to tell the public, 'Well, doctors have no clue.' Well, that's not exactly the case, especially in specialty areas," Gill said.

Industry is trying to "change the conversations into one-on-one conversations that really can't be monitored or regulated at all." – Georgetown's Fugh-Berman

Adriane Fugh-Berman, a Georgetown University professor and director of PharmedOut, a research and education project that analyzes the effects of pharmaceutical marketing on prescribing practices, said FDA needs to regulate off-label promotion more, not less, and this includes regulated industry-funded CME.

"The fact that industry-driven avenues of communication already exist is not justification for dropping all barriers," she said. New uses of approved medicines "should be discussed in scientific meetings. They can be discussed in medical journals."

"Industry is trying to get around this to change the conversations into one-on-one conversations that really can't be monitored or regulated at all, and there are already good and self-correcting venues for having these discussions, and that's where it should be," Fugh-Berman said. "These discussions should be public. If it's really scientific exchange, then it should be done in a scientific format. And if they really have great evidence from randomized, controlled trials, then they should be applying for an indication and a label change."

Sharfstein Weighs In

The FDA panel also heard from former agency Deputy Commissioner Joshua Sharfstein, who is now associate dean for public health practice and training at Johns Hopkins University.

Like other speakers, Sharfstein questioned "what is the greater advantage of off-label communication over and above what's allowed."

"What is the greater advantage of off-label communication over and above what's allowed?" – Johns Hopkins' Sharfstein

"We're not talking about whether things can be communicated at all," he said. "It's above and beyond the medical literature, professional communications, clinical practice guidelines, and the permitted practices of answering questions and distributing peer-reviewed research."

Sharfstein said that although there may be some cases where there are benefits of more off-label promotion, "it would exist in narrow specific circumstances and FDA should review that basic setting and really be able to feel comfortable that there's value."

Despite the skepticism voiced by many of the second-day speakers, some change in FDA policy seems inevitable. The meeting also included discussion of how FDA would pay for the additional reviews of off-label materials that it may soon undertake. (Also see "Off-Label Communication Growth: Could FDA Afford To Police It?" - Pink Sheet, 10 Nov, 2016.)

Rare Disease Groups Back Off-Label Communications

Some patient advocates had a different view on the need for more off-label communications, particularly in the rare disease setting.

Katherine McGahey with the 1 Million 4 Anna Foundation, a Ewing's sarcoma patient advocacy group, said that when it comes to pediatric cancers, off-label use is the norm.

"No one has died from too much truthful, non-misleading information," she said, distinguishing between promotion and communication. "When you impede the flow of information, our children die."