What does 'breakthrough' mean to docs and consumers? It's not the FDA definition

Dartmouth Institute Steven Woloshin
Dartmouth Institute researchers and physicians Steven Woloshin and Lisa Schwartz. (photo by Dartmouth-Hitchcock)

According to the dictionary, the word breakthrough means “a sudden, dramatic and important discovery or development.” However, what many doctors don’t know is that it doesn’t have the same meaning in the FDA drug approval process. 

Some 77% of physicians think when the FDA designates a drug as a breakthrough therapy, it means there is “high-quality evidence” that the drug is more effective than current treatments, according to a study recently published in the Journal of the American Medical Association. The reality is that the FDA can give drugs a breakthrough therapy designation simply if early clinical evidence suggests an advantage over current options for serious or deadly diseases.

“When you hear the word breakthrough, it’s understandable to think that it means something definitively or a game changer,” said study co-author Dr. Steven Woloshin, a professor of medicine at the Dartmouth Institute. “But it gets confusing because the FDA uses it in a very different way.”

The problem--confusing the dictionary definition with the FDA usage--stems back to the birth of the designation. In 2011, advocates led by nonprofit Friends of Cancer Research lobbied Congress to expedite approval for promising drugs to treat serious or life-threatening diseases by creating a breakthrough therapy designation, meant to ensure patient access to emerging “revolutionary” drugs as quickly as possible. Bipartisan lawmakers senators Orrin Hatch (R-UT), Michael Bennet (D-CO), and Richard Burr (R-NC) introduced the “Advancing Breakthrough Therapies for Patients Act,” and it was passed into law in July 2012 under the FDA’s Safety and Innovation Act.

Some of the same scientists are authors of the new study, including Woloshin, who did a similar study with general consumers on the “breakthrough” drug designation last year. In the earlier study, they discovered that the words “breakthrough” and “promising” increased consumers’ positive beliefs about a drug’s effectiveness by double-digit percentages. When people were asked which drug they would take for a possibly deadly condition, one labeled breakthrough or one not, 92% chose the breakthrough drug. 

However, “breakthrough” isn’t the only problem. The newer study also found inaccurately optimistic beliefs among doctors simply over FDA approval of a drug. Seventy-three percent of doctors believed that FDA approval of a drug meant the treatment was just as effective as other drugs already approved. 

The overall effect of all of the misunderstandings regarding the FDA approval process and the breakthrough designation is that people and doctors are potentially more enthusiastic about new drugs than maybe they should be.

“The FDA has a number of programs to expedite drugs, and that’s a good thing,” Woloshin said. “There’s no question, especially for drugs for conditions that are really serious or there aren’t any treatments at all available, that it’s really good to try to move things through the process quickly provided the FDA maintains standards and is transparent. We’re just saying the terminology that they use can confuse people and can mislead doctors and patients into believing that drugs are more effective or safer than what the data say.”

- see the 2016 and 2015 studies in JAMA
- read the FDA fact sheet on breakthrough therapies