Drug and medical device makers, insurance companies, lawyers and patients packed a room for two full days of public hearings at the Food and Drug Administration's campus in Silver Spring, Maryland, this week to debate those rules.
A lot is at stake: Companies spend about $27 billion a year to market their products.
Dr. Robert Califf, the FDA commissioner, said that ultimately, the review of the regulations is to ensure that the system "best protects and promotes the public health and the well-being of patients."
What is the solution? It depends on whom you listen to.
Companies testified that current marketing regulations are too restrictive. Words like "chilling," "stifling," "a limit to innovation" and a "violation of the First Amendment" were often used in their testimony.
Patients who testified, some of them through tears, argued that loosening these rules would be a "public health disaster." Wider marketing, they believe, would lead to more conflicts of interest, which could lead to patient harm and even death and could further erode the authority of the FDA. Even with the current regulations, there are a number of cases of people who were harmed.
Here's how the issue could affect you.
How the rules work now
To get FDA approval for a drug or medical device, a company must put its product through a rigorous and expensive testing process. It then submits medically sound data to the FDA to prove that the product works.
If the company gets FDA approval for a specific use of a product, it can market the product
only for that. Marketing includes advertising and communication, such as training with doctors.
Your doctor, however, doesn't have the same limitations. They can use a drug or medical device in any way they see fit and recommend that use to colleagues, even if there wasn't FDA approval for that particular illness, dosage or demographic. As long as the doctor thinks it will be safe and effective, they can use the drug or device in what the industry calls an off-label fashion.
The 'off-label' dilemma
Doctors prescribe off-label drugs frequently, studies show,
although the majority of patients don't know that the drug they are taking may not be approved
for use in that way.
Doctors have no legal obligation to tell you, even though studies have found that off-label drugs more often cause harm than those that have been tested for a specific purpose, and 80% of off-label prescribing is not based on strong medical evidence
. That could be a problem, as about two-thirds of patients in a
new survey said that if they had known their drug was off-label, they would not have taken it.
But there can be benefits.
Pediatricians often use drugs off-label, since many pharmaceutical companies don't test their medications on children. Oncologists often use off-label drugs when there is no other approved option to treat a certain cancer.
Doctors who work with rare diseases, mental illnesses or diseases that don't have a lot of FDA-approved options also prescribe them. In the case of lupus, its two main standard treatments are off-label, the Lupus Foundation said at the meeting Wednesday.
A company must file a supplemental drug application if it wants to expand the list of maladies a drug or device is approved to treat. Some companies don't bother, because the cost of that application may never be offset by the revenue generated from newly approved uses.
That's where doctor discretion can come in. Though doctors do have a wide variety of information available to them about the way off-label drugs and devices work, including studies in journals, Clinical Practice Guidelines and information requested
about them from firms, pharmaceutical companies are also eager to speak with them further
about off-label possibilities.
Pharmaceutical companies want to be able to train and communicate with doctors about off-label uses in order to share information, but doing so is prohibited by the FDA.
"Manufacturers are the best experts on our own medicine," testified Pfizer's Dr. Andrew Koening.
Sandra Kalter, who testified on behalf of the medical device manufacturer Medtronic, complained that "innovation is chilled" and that it's hard to keep doctors up-to-date.
Kalter added that even if a company learns about risks associated with off-label use, it is not allowed to communicate that to doctors.
Dr. Edith Perez, who testified on behalf of the device maker Genentech, said she learned about a leukemia drug that showed "unprecedented" success for 25 out of 26 patients, but because it was off-label, the company was not allowed to tell patients who might be helped by it.
Looser rules would let the industry help doctors cut through the volume of studies that come out each month.
The companies also argued that these regulations violate their First Amendment rights to free speech. A couple
(PDF) of recent court decisions
(PDF) followed that reasoning.
Danelle Miller, who testified for Roche, explained anyone else can communicate with the doctor about off-label use -- nonprofit groups, professional associations, other doctors -- but the companies that make the products can't.
"The more questions we can answer, the more lives we can save," Miller said.
At least one company admitted that it had decided on occasion to ignore these regulations if doing so could save a patient's life. But that has produced mixed results.
The problems with off-label
Johnson & Johnson subsidiary Acclarent paid the government $18 million this summer to settle False Claims Act allegations that the company violated these regulations.
The FDA cleared use of the company's Stratus sinus device with saline solution, but a Department of Justice statement said the company never intended to use it this way. Instead, the company designed Stratus to be used with corticosteroids, a class of drugs used to treat immune system problems, inflammation and other issues.
A company training video showed Stratus being used with the corticosteroid, even though the FDA rejected the company's 2007 request to expand the approved uses to include that drug. In January, Acclarent's former CEO and its vice president of sales will be sentenced for introducing an adulterated and misbranded medical device into interstate commerce.
Without the proper testing required by FDA approval, drugs used off-label can also be dangerous and "expose patients to risky and ineffective treatments," according to a 2009 study
An example used in the public hearing concerned the off-label use of Fen-Phen. The FDA approved the drugs phentermine hydrocholoride and fenfluramine hydrochloride separately, but some doctors started telling patients to use them together, after an article described dramatic weight loss from the combination. Many patients did lose weight, but this off-label use gave some severe heart valve problems. The drugs were taken off the market in the 1990s.
Critics say that if the regulations are any looser, it could lead to waste, fraud and even more danger. A number of people told the FDA that they'd been harmed by off-label use and tried to make a case against relaxing regulations.
When a driver hit Jeremy Lew, a California-based screenwriter who worked on the TV show "Miami Vice," hurting his neck, doctors used a device in an off-label way that further injured his neck. He has not fully recovered from that 2009 surgery.
Through tears, he described the deep, life-altering pain created by this device and the surgeries he needed to repair the damage. "If these are the liberties the FDA is already extending to industry, imagine what will happen should the regulations be loosened," he said.
Other experts testified that pharmaceutical companies already have ways to communicate about how to use their drugs off-label.
Linda Gill, now with Consumer Reports, used to ghost-write continuing education materials for the pharmaceutical industry.
"I'm embarrassed to say we would use terms like 'emerging therapies' or 'advancement in clinical practice,' " and those were "code for off-label drug uses" that were well-known, she said. The companies would also use well-known paid consultants to communicate messages about off-label uses.
"My point here is that this mechanism definitely already exists," she said. "It is a well-oiled machine."
Loosening the regulations would "undermine the integrity of the FDA drug approval process," argued Sarah Christopherson of the National Women's Health Network
When it comes to medical devices, Madris Tomes, a former public health analyst with the FDA, who now runs her own company Device Events, testified that she used the agency's own database to pull data about adverse events related to off-label uses.
She found that for the past 20 years or so, there have been at least 23,809 adverse event
s reports that reference off-label use of a medical device. Over 14,000 involved injuries, and 777 patients died. And that's only reported incidents, which are probably on the low side: A 2009 report from the Office of the Inspector General found that only 14% of adverse events are reported to the FDA, and 99% of those reports went through the manufacturer first.
There are also concerns that if more marketing is available about these drugs, more doctors will chose the newer ones because they've heard so much about it, regardless of its effectiveness. It's a problem even now.
"Overuse is a big national problem," said Dr. Vikas Saini of the Lown Institute, a health care reform group. "Even without the looser restrictions."
Saini argues that an abundance of caution with these off-label uses of drugs is always warranted. An independent arbiter like the FDA is always necessary. Otherwise, he said, "we risk the explosion of 21st-century snake oil."
The FDA will consider the oral testimony and will get written suggestions by early January.
The agency will compile these suggestions into a larger document and can, at some point, decide whether it should change the longstanding rules that govern speech as it involves the use of off-label drugs and medical devices.
There is no timetable for that decision.