TUESDAY April 12, 2016, 2016 — Use of the word “breakthrough” in the U.S. Food and Drug Administration expedited approval process could mislead doctors about the new drugs’ actual benefits, researchers warn.

The U.S. Congress in 2012 gave FDA the power to designate a drug as a “breakthrough
therapy” if preliminary clinical evidence suggests an advantage over existing medications.

But a survey of nearly 700 doctors revealed that many tended to misinterpret “breakthrough.” Doctors often believed the drugs were supported by stronger evidence than the law requires to achieve that designation, said lead author Dr. Aaron Kesselheim. He is a faculty
member at Brigham and Women’s Hospital in Boston.

“When people hear ‘breakthrough,’ it gives them an inappropriately elevated sense of what the drug might do,” Kesselheim said. “It may give physicians false reassurance about the outcomes they might expect to receive when they prescribe it.”

In the survey, nine out of 10 doctors chose one hypothetical drug over another identical one solely based on the “breakthrough” designation, even though both were taken on the same schedule, had similar side effects, and were equally covered by the patient’s insurance.

In addition, 52 percent incorrectly believed that strong evidence from randomized trials is needed to earn the breakthrough designation, the researchers found.

“They thought when a drug is labeled as a breakthrough therapy it actually is a breakthrough, and that’s not necessarily the case,” Kesselheim said. “Many drugs labeled as breakthrough therapies are not true
breakthroughs, because they don’t provide substantially advanced treatment over what’s already available.”

The results were published April 12 in the Journal of the American Medical Association.

Brawley also said he is “convinced there are still some doctors who still tend to think the new drugs are better than the old drugs.”

He noted the case of Prilosec, a heartburn medication made by AstraZeneca. When it came time for Prilosec to go generic, AstraZeneca marketed a new heartburn drug called Nexiumfor which it could still charge premium prices.

“They never said that Nexium simply contained the same active ingredient as their old drug Prilosec,” Brawley said. “If you’ll recall, Nexium became one of the best-selling drugs for years. There are people who are surely prescribing it because it is newer.”

For more on “breakthrough” therapies, visit:
U.S. Food and Drug Administration.

• FDA Alert: Proton Pump Inhibitors (PPIs) – Drug Safety Communication: Clostridium Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs, February 8, 2012

• AcipHex (rabeprazole sodium)
• Dexilant (dexlansoprazole)
• Nexium(esomeprazole magnesium) 
• Omeprazole (omeprazole) Over-the-Counter (OTC)
• Prevacid (lansoprazole) and OTC Prevacid 24hr
• Prilosec (omeprazole)  and OTC
• Protonix (pantoprazole sodium)
• Vimovo (esomeprazole magnesium and naproxen)
• Zegerid (omeprazole and Sodium bicarbonate) and OTC

 ISSUE:
FDA notified the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve. The FDA is working with manufacturers to include information about the increased risk of CDAD with use of PPIs in the drug labels.

FDA is also reviewing the risk of CDAD in users of histamine H2 receptor blockers. H2 receptor blockers are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and heartburn.

BACKGROUND: Proton pump inhibitors (PPIs) are marketed under various brand and generic drug names as prescription and over-the-counter (OTC) products. They work by reducing the amount of acid in the stomach. Prescription PPIs are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus. Over-the-counter PPIs are
used to treat frequent heartburn.

Clostridium difficile (C. difficile) is a bacterium that can cause diarrhea that does not improve. Symptoms include watery stool, abdominal pain, and fever, and patients may go on to develop more serious intestinal conditions. The disease can also be spread in hospitals.  

RECOMMENDATION: Patients should immediately contact their healthcare professional and seek care if they take PPIs and develop diarrhea that does not improve. Information for Healthcare Professionals:

• A diagnosis of CDAD should be considered for PPI users with diarrhea that does not improve.
• Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs.
• Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

To learn more

[02/08/2012 – Drug Safety Communication – FDA]