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FDA to Clarify Position on Off-Label Uses of Drugs

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Off-label use of prescription medications, a common practice that healthcare providers have long relied on and that pharmaceutical companies have profited from, has become the subject of a great deal of controversy. Billions in settlements have been paid out to patients who were allegedly harmed as a result of the off-label use of prescription drugs such as Zofran and Risperdal. Now, drugmaker Amarin Pharma has attempted a pre-emptive strike – not against patients who might file Zofran or Risperdal lawsuits, but against the FDA, whom Amarin Pharma claims is violating its First Amendment rights.

The pharmaceutical company has filed a lawsuit against the government agency, claiming that its right to free speech has been inhibited by FDA regulations that prohibit the promotion of medications for uses that have not been approved by the agency. The FDA is also facing pressure from Congress. A new bill, 21st Century Cures, proposes to accelerate the introduction of new drugs into the stream of commerce. If it’s signed into law, the FDA may consider adding more wiggle room to its guidelines. Regardless, agency representatives will discuss these matters during a public meeting this summer.

Current FDA rules

Under the current regulations, the FDA allows healthcare providers to prescribe a medication for whatever purpose they deem appropriate. For example, trazodone is an antidepressant that may also be prescribed for insomnia. Zofran is an anti-nausea medication approved for use by surgery and cancer patients, yet it was sometimes prescribed to pregnant women to combat morning sickness. And Risperdal, which is an antipsychotic, has been prescribed to treat symptoms of attention deficit hyperactivity disorder (ADHD).

However, while a doctor could prescribe a drug for off-label use, it is against FDA regulations for a pharmaceutical company to actively promote a medication for a use for which it has not been approved. In 2013, Johnson & Johnson agreed to pay more than $2.2 billion to resolve civil and criminal investigations that concerned allegations involving payments of kickbacks to physicians and the promotion of Risperdal for off-label uses. More families may continue to file Risperdal and Zofran lawsuits.

Current regulations do allow pharmaceutical companies to give doctors information from well-controlled clinical trials that were published in reputable reference texts and medical journals. They are not allowed to give doctors information from early clinical trials. These companies are even allowed to discuss off-label uses of drugs during medical conferences and respond to unsolicited questions from doctors about their products, so long as they give equal attention to the drug’s risks as well as potential benefits. However, pharmaceutical companies want free rein to discuss information that arises from pre-clinical trials, which may have more questionable results.

Many healthcare experts are opposed

Some healthcare experts have vehemently opposed relaxing FDA regulations, arguing that a decision in favor of freedom of speech could compromise public safety.

“People do not realize that the consequences of this new ideological approach to the First Amendment will be measured in lives,” said Dr. Joshua Sharfstein, a former principal deputy commissioner at the FDA.

Often, the real dangers of a drug are not well known until it has already been in use for many years. Elderly patients with dementia were previously given drugs to treat schizophrenia (an off-label use), yet this practice was later revealed to increase mortality among elderly patients.

Premarin, a menopause drug, was widely prescribed to reduce the risk of coronary disease, yet it was later determined that patients suffered an increased risk of heart attack and stroke instead.

Furthermore, if drug companies are allowed to distribute data from early trials, there is a possibility that this data would not reflect an accurate safety profile. A study published in 2012 revealed that up to 75 percent of pre-clinical trial results were not reproducible.

Possible FDA proposals

At the FDA public meeting this summer, the agency is expected to discuss two of its recent proposals. The agency is considering allowing pharmaceutical companies to distribute clinical practice guidelines to healthcare practitioners. These sometimes include suggestions for off-label use. The FDA is also considering allowing companies to provide medical literature that suggests the side effects on the label of a product might be exaggerated.

  1. Reuters, Under pressure, FDA to hold public meeting on off-label use,
  2. The New York Times, Drugmaker Sues F.D.A. Over Right to Discuss Off-Label Uses,
  3. The U.S. Department of Justice, Johnson & Johnson to Pay More Than $2.2 Billion to Resolve Criminal and Civil Investigations,