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HEALTHLINE NEWS

The Debate Over ‘Off-Label’ Drug Uses

The battle is intensifying over whether companies should promote their drugs and whether doctors should prescribe them for uses other than approved by the FDA.

off-label drug use

As a screenwriter, Jeremy Lew creates fiction for a living.

As a patient, he found fact stranger than fiction.

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In 2009, while bringing his newborn son home from the hospital, he was struck by a hit-and-run driver.

His son escaped without injuries. Lew, however, underwent surgery nearby at the University of California, Los Angeles (UCLA), where a surgeon inserted a plastic device and synthetic grafting material.

Things seemed better … for a while.

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By 2012, Lew was in “unrelenting” pain and could barely pick up his children. Further surgeries at other facilities would help ease his discomfort, but he continues to have health problems.

As it turned out, the device implanted in Lew’s neck wasn’t designed for the small bones in the cervical spine.

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The surgeon who performed the procedure was using the device “off-label,” or for something not approved by the Food and Drug Administration (FDA). That doctor was also being paid by the company that made the device, according to government records.

To Lew, these details he learned years after his accident spotlight a crucial point in the doctor-patient relationship. Among other things, Lew said, it creates more conflict of interest and takes away a patient’s ability to legally consent to a procedure involving significant rik devices.

The device was approved by the FDA for use in the mid- to lower spinal column, even though medical experts have said the device is too small to fit there. Instead, surgeons are opting to use it in the smaller and more anatomically complicated cervical spine.

“If you would try to put it there, you would kill the patient,” Lew told Healthline. “It’s like using a pair of gloves as a pair of shoes.”

Since his procedure and subsequent legal action, Lew has been an advocate against the off-label use of medical devices and medications.

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“It’s a scam,” he said.

Read more: What’s wrong with our prescription drug trials? »

A push to loosen ‘off-label’ recommendations

Currently, the FDA forbids manufacturers from directly marketing uses for a drug or device that haven’t been approved by the agency.

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Those uses and the drug’s side effects must be listed on the side of the drug or device’s packaging for doctor and patient review. These are known as “on-label” uses.

However, physicians are allowed under FDA rules to prescribe drugs or devices for uses other than what the drug was initially approved for. The thinking is that if a drug is safe, it’s safe no matter what condition you are using it for.

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This practice is known as “off-label.”

There are reasons doctors would resort to off-label uses, namely in the cases of patients with rare or terminal illnesses.

Rare diseases are less likely to be researched because there are fewer profits to be gleaned from sparsely used therapies, while doctors are going to try the best medicine available for patients who are facing potentially fatal illnesses.

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A 2007 report in JAMA Medical News and Perspectives suggests that up to 75 percent of drugs used in cancer care in the United States are used off-label. Up to 90 percent of people with rare diseases are given at least one drug off-label, and three-fourths of drugs on the market don't have indications for use in children.

That’s changed a lot of lives. For the better, and for the worse.

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Read more: Why the antibiotic pipeline is running dry »

Concerns over off-label uses

Getting FDA approval for a drug — for labeled uses — requires a large investment, in both time and money. These costs are footed by people set to reap the largest financial benefit.

Both sides of the proverbial medical coin don’t dispute that.

The problem lies in the standard of scientific evidence and medical necessity that brings a drug or device to market and what they can be used for.

One side wants the relationship between medical corporations and doctors to be closer, while others object.

Proponents of off-label uses have even invoked the First Amendment, saying companies have the right of free speech to promote their products.

However, opponents fear increasing the influence drug and device makers have over the doctor-patient relationship could do more harm than good when companies are contractually obligated to reap profits for their shareholders.

What is to prevent a company from promoting a drug off-label for a condition for which the company already knows the drug is ineffective?
Dr. Adriane Fugh-Berman, Georgetown University Medical Center

One of those people is Dr. Adriane Fugh-Berman, an associate professor of pharmacology and physiology at Georgetown University Medical Center. As the director of PharmedOut.org, a nonprofit organization dedicated to exposing the effects of pharmaceutical marketing on prescriptions, she’s a critic of off-label promotion.

Fugh-Berman was one of dozens of people to testify at the FDA hearings about off-label promotion in November. She testified that drug companies don’t seek labeled indications because they’re afraid the benefits of the drug won’t outweigh the risks, among other things.

“What is to prevent a company from promoting a drug-off label for a condition for which the company already knows the drug is ineffective?” she testified.

She also spoke about ways companies can circumvent the FDA process. One such way is having industry insiders ghostwrite commentaries about off-label uses of drugs in medical journals — with or without peer review — which are then distributed to doctors.

“It’s really off-label promotion,” she told Healthline. “It’s terrible for public health.”

Off-label communications, properly done, advances precision medicine, delivering speedier positive patient outcomes.
Peter J. Pitts, Center for Medicine in the Public Interest

At the hearings, drug manufacturers and device makers expressed the benefits that could come of expanding their ability to recommend similar off-label uses to doctors.

These include increasing a patient’s options for treatment, less dependency on direct-to-consumer advertising, and the ability to disseminate observational data, which, in the scientific and medical community, is considered the weakest form of evidence.

Peter J. Pitts, a former FDA associate commissioner, and president of the Center for Medicine in the Public Interest — an industry-funded nonprofit — filed testimony in favor of loosening restrictions.

“Off-label communications, properly done, advances precision medicine, delivering speedier positive patient outcomes, and reducing costs to our healthcare system,” he wrote. “Off-label communications provide patients with more options for effective medicines.”

Some critics, like Fugh-Berman, disagree, and say current practices, like corporate ghostwritten articles in biomedical journals, highlight a problem that doesn’t need to get worse.

Read more: Taking drugs the correct way »

A settlement for ‘off-label’ use

Lew also testified at the FDA hearings, telling agency heads about his experience with his cervical implant and grafting material, as well as the subsequent complications.

“I’m here to speak for those whose lives were ripped away by something no bigger than a dime, that can only fit into the neck, yet the labeling states it’s not supposed to be there,” he testified. “If these are the liberties that the FDA is already extending to industry now, imagine what will happen should off-label regulations be loosened.”

Lew’s story, however, does have some closure, at least for now.

In July, he was part of a two-plaintiff lawsuit settlement against Medtronic, the makers of his device, and the UCLA Health system.

The lines have become so blurred.
Jeremy Lew, surgery patient

According to Lew’s lawsuit, a representative of Medtronic was in the operating room while a device was surgically implanted in a crucial part of his body. Also, the doctor who performed his surgery didn’t disclose his financial conflict of interest with Medtronic.

No party admitted any wrongdoing.

“[The doctor] was not paid for using the Medtronic products used in the surgery, and as of the time of the surgery involving Mr. Lew, he was not a consultant for Medtronic,” the company said in a statement to the LA Times.

While Medtronic’s payout remains undisclosed, Lew’s settlement with the U.C. Board of Regents was $4.2 million.

Lew couldn’t comment on the settlement, but he did say lowering the standards of communication between drug and device manufacturers and medical professionals will continue to erode the doctor-patient relationship.

“The lines have become so blurred,” he said.

Those lines may become even more indistinguishable in the near future.

Last March, the FDA reached a settlement with Amarin Corporation that allows the company to engage in truthful and nonmisleading promotion of its fish oil product, Vascepa, for off-label uses.

A blog on healthaffairs.org stated the decision “marks a significant change in FDA policy for an off-label use.”

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