Debating whether drug and device companies should be able to discuss scientific information about the off-label uses of their products may be an interesting academic exercise for some, but access to that information could be a matter of life or death for patients whose only treatment options are off-label.
That's the point Katherine McGahey made Thursday during the FDA's public hearing on what companies can say about their products and to whom they can say it. Speaking on behalf of the 1 Million 4 Anna Foundation, McGahey noted that in a vacuum of reliable information, useless and often dangerous snake oil remedies will flourish.
"The absence of information fuels . . . nonsense," she told the FDA panel.
McGahey took issue with hours of testimony from attorneys, consumer advocates and patients harmed by off-label uses who confused the exchange of scientific information with promotion. Citing personal experience and the billions of dollars in fines assessed against companies for repeated off-label promotion, many of the speakers warned the FDA that any loosening of its regulations on industry speech would lead to disastrous consequences.
Looser standards could further blur the fine line between product promotion and the exchange of scientific information, said Jeanie Kim, a research scholar at Yale Law School.
Promotion and communication are not the same thing, McGahey countered. Saying that a company sharing reliable, needed information with a doctor and patients is the same as a TV ad is callous and insulting, she claimed.
Patients and their families need transparency and a two-way flow of information, McGahey said, noting that it's often up to them to research possible options, especially when it comes to rare pediatric cancers, because oncologists don't always have the time and resources to do that research. Recognizing the varying reliability of available data, she advised that companies be required to disclose the source of information they share and to protect its integrity.
Bristling at testimony condemning all off-label use and questioning doctors' ability to weigh the information, Doyle Stulting, of the American Society of Cataract and Refractive Surgery, said that in many cases, doctors would be guilty of malpractice if they didn't use some products off-label, as that may be the standard of care.
Doctors understand the development of scientific data and are skeptical about case reports, Stulting said. While they have confidence in randomized, controlled trials, doctors can't always wait for the FDA to update labeling based on those trials. Yet current regulations interfere with companies sharing that information. He recommended that companies be required to inform doctors when they're sharing off-label data and that they be restricted to providing only truthful and non-misleading information. He also suggested including a paragraph in the labeling to the effect that the label is based on clinical trials, but after-market use may provide new data about a product's safety and efficacy.
Several of those urging the FDA to maintain or strengthen its regulations about off-label communication were patients who were harmed by the off-label use of drugs. In every instance, they were unaware the drug was being prescribed off-label. They called on the FDA to require patient informed consent before such use. However, the agency can't regulate medical practice.
There are things the FDA can do. For instance, it could quicken the pace in which it shares safety information about off-label uses. The agency takes two months to two years to recommend a device recall when adverse events occur, Device Events founder and CEO Madris Tomes said. That delay means doctors don't always have the best advice to share with their patients or inform their decision-making.
As of Sept. 30, Tomes said that, according to the agency's database of device adverse events reports (AERs), nearly 24,000 adverse events – including more than 14,000 injuries and 777 deaths – have been associated with the off-label use of devices.
Even more concerning are adverse events associated with uses that are contraindicated on the label. Tomes cited 5,121 such AERs, including more than 3,400 injuries and 461 deaths. She noted that many of the AERs are based on reports doctors submitted to the companies. She said doctors should be able to submit them directly to the FDA.
As a basis for defining new regulatory standards on sharing truthful, non-misleading information with health care payers and professionals, Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization are proposing nine principles grounded on a commitment to science-based communication, the provision of an appropriate context about the data and an accurate representation of that data.
New standards are needed, given an increasingly data-driven, value-based health care system in which prescribing decisions are no longer made by independent physicians, PhRMA President and CEO Stephen Ubl said when the principles were released this week.
Today, prescribing decisions are influenced by integrated delivery systems or financial incentives created by health plans. "In this changing environment, it is important that biopharmaceutical companies be able to share appropriate science-based information" with the true decision-makers, Ubl said. But that's not possible under current federal regulations.
For instance, restrictions on conversations between drug companies and payers before a drug is approved could stymie efforts to move to a value-based pricing system, Holly Campbell, senior director of communications at PhRMA, told BioWorld Today. Such restrictions also leave payers unprepared when transformative, disease-modifying therapies come to market. (See BioWorld Today, Nov. 8, 2016.)
Those opposed to letting industry have those conversations fear such exchanges would be fueled by their bottom line and would undermine the FDA's review processes, as companies would have no incentive to conduct trials for new indications. Increased off-label use also would discourage patients from participating in trials, Kim said.
FDA officials noted that much off-label use involves drugs that have gone generic. They asked who's going to conduct those trials.
In addition to requiring patient informed consent for unapproved uses, opponents encouraged the FDA to improve training for doctors about off-label prescribing, use plain English and brand names when issuing safety information and updating label warnings, and develop a database of off-label experiences.
FDA Commissioner Robert Califf repeatedly expressed the need for such a database that could show when and why doctors use a product off-label and what the results were. While the agency doesn't have the authority to require that information from doctors, he wondered whether they would be willing to provide it.