FDA hearing on off-labels use of devices explores risks to patients

SILVER SPRING, MD. – First, health policy expert Diana Zuckerman displayed huge photos of the disfigured, bruised faces of two babies who had been implanted with Medtronic's Infuse Bone Graft product in their skulls.

Then Zuckerman, who is president of the National Center for Health Research, put up on the same projector screen the language of the Food and Drug Administration's 2015 warning that the product had never been approved for use in children and could be dangerous for them. The warning does not include the commercial name of the Medtronic product, nor does it include a ban on using it in kids.

"That's a pretty calm and un-disconcerting warning, especially when they don't even name the products," Zuckerman said Thursday during a presentation on the second day of a two-day FDA hearing. The agency called the meetings to gather fresh perspective on a growing conflict it faces in trying to regulate whether companies can use First Amendment rights to promote uses of devices and drugs that have not been studied.

The first day of commentary aired the perspectives of medical-supply companies who chafe at the FDA's tight restrictions on commercial speech.

The second day of the hearing included stories of patients who were injured after devices and drugs were used on them in unapproved ways, including Medtronic's Infuse Bone Graft.

The perspectives of injured patients drove home the stakes in an ongoing legal and ethical debate over what companies can say and do when they sell products for uses not described on the FDA-approved labels.

Doctors are legally allowed to use devices and drugs in unapproved ways that they think will benefit patients. The question for the FDA is how far manufacturers should be allowed to go in explaining products for applications the FDA has neither approved nor cleared, a practice known as off-label use.

Zuckerman said the Infuse Bone Graft is "contraindicated" for children. But the FDA's 2015 warning didn't ban the product in kids because some children have such significant bone defects or such rare bone disorders that they would be willing to accept the risks.

Although both kids and adults are susceptible to risks from Infuse like excess bone growth, kids are more vulnerable because their bones are still growing and they have less space to absorb unexpected swelling.

Medtronic has repeatedly denied allegations in lawsuits that it promotes Infuse for off-label uses.

Asked Thursday about Medtronic selling Infuse to children's hospitals, spokesman Fernando Vivanco said via e-mail: "Medtronic's company policies and extensive training expressly provide that we promote our products only for those uses that are consistent with the labeling approved by the FDA. If a licensed hospital contacts us to order one of our products, it would be inappropriate to make assumptions about the intended use or ultimately interfere with a physician's judgment about patient treatment."

The parents of Hailey Reuter, whose injury photo was one of the two Zuckerman displayed at the FDA hearing Thursday, have said in a lawsuit that no one informed them Infuse was going to be used in what they called an "experimental" surgery on their 5-month-old daughter at a children's hospital in Cincinnati.

"Most consumers have no idea when they are given a drug or device off-label," Minnesotan Kim Witczak told the FDA panel Thursday. Witczak became a patient advocate after her husband killed himself in 2003 after being prescribed the antidepressant Zoloft for insomnia, which she blames for causing his death.

Witczak was among roughly 30 witnesses Thursday, most of whom said companies don't need more leeway to spread information about product applications on which the FDA has not ruled.

The comments offered a counterpoint to the hearing's first day, when dozens of trade groups, industry lawyers and companies argued that the First Amendment guarantees companies a constitutional right to communicate about off-label uses of products and to train doctors in those uses, so long as those promotions are truthful and not misleading. Some lawyers argued that commercial speech cannot be restricted even if it could hurt people.

Challenges in medical treatment of children were a common theme at Thursday's hearing. Some speakers noted that off-label use of medical products in kids is virtually inevitable, because so few products have been approved for them.

Katherine McGahey, whose daughter has cancer, said off-label use saves the lives of children who do not have time to wait for research. Communication about off-label options is different from commercial "promotion" of those uses, McGahey said, in calling for broader dissemination of information about off-label uses.

Steven Francesco, who said his son died from careless off-label prescribing, believes the answer is a strong commitment to much more pediatric research.

"Seventy to 90 percent of medications prescribed to children is off-label," said Francesco, a former pharmaceutical executive. "Where you have no data, you have the Wild West."

Jim Spencer • 202-662-7432

Joe Carlson • 612-673-4779