'Breakthrough' confusion prompts FDA to explain its terms

FDA sign

What does "breakthrough" mean? The FDA set out to explain the designation last week after academic studies and the media reported widespread confusion about the term.

The FDA posted a two-part Q&A on its website addressing more than just the breakthrough tag. Dr. Richard Moscicki, deputy director for science operations at the Center for Drug Evaluation and Research, outlined the terminology of all of the FDA’s expedited programs, specifically addressing the “breakthrough” issue first.

“Perhaps we should have used the term ‘potential breakthrough’ when the program was named to cut down on confusion," he said, "although I suspect it even then that the word 'breakthrough' would have appeared on its own in media stories."

Moscicki goes on to reveal stats-to-date about the breakthrough therapy program. Since it began in 2012, CDER has received 342 requests from pharma companies and granted 111 breakthrough designations. Of those 111 drug candidates, 41 have gone to market.

About half of the breakthrough-designated drugs approved are cancer drugs, with remaining drugs divided between infectious disease, rare inherited disorders and “other.”

However, just recognizing the confusion isn’t enough, one researcher said. “I think it’s good that they’re acknowledging that there’s a problem, but clearly the best thing would be to abandon the term and use different terms," said Dr. Steven Woloshin, professor of medicine at Dartmouth Institute and an author of two academic studies showing consumer and physician confusion over FDA's expedited programs.

"These are marketing and advertising terms, like breakthrough, and part of FDA’s job is to regulate advertising, not participate in it," he said.

In studies, Woloshin and his colleagues found that consumers and physicians mistakenly substitute the dictionary version of “breakthrough”--meaning a sudden, dramatic and important discovery--when they hear about the FDA designation. However, under the FDA program, the status is granted simply to drugs that show early clinical promise, which may or may not continue to be the case as the drug moves through the approval process.

The term “breakthrough” seems to have originated at the FDA during the early stages of the program's development. An FDA spokeswoman said CDER Director Dr. Janet Woodcock recalls that she first brought up the term "breakthrough" during initial FDA discussions about ways to expedite certain drugs. As Woodcock remembers, the term then began being discussed more widely among advocates and legislators.

The result of the designation--along with four other expedited approval programs the FDA uses--has been the passage of more drugs more quickly. Whether that’s good or bad depends on your perspective. Friends of Cancer Research, one of the original organizations that lobbied for the breakthrough program, recently published a study of the cancer drugs approved through the program and concluded the breakthrough program has had a positive impact in oncology.

However, as The New York Times reported last year, speedy drug approvals are now the rule instead of the exception. The article quoted Dr. Aaron Kesselheim, an associate professor of medicine at Harvard Medical School who worked on a breakthrough terminology study with Woloshin. The article said the popularity of the expedited programs could be worrisome because the quicker pathways to approval “typically require less evidence of a drug’s efficacy or safety than the standard process.”

Quoting Kesselheim, the article said, “These pathways were intended for very urgent circumstances of serious life-threatening conditions, or no other reasonable clinical alternatives. They were originally intended as the exceptions, but now the exceptions are beginning to swallow the rule.”

- see FDA blog post
- review the FOCR paper published in Nature
- read NYT article (sub. req.)

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