Regulatory Focus™ > News Articles > Physicians Lack Understanding of What ‘Breakthrough’ Designation Means, Study Finds

Physicians Lack Understanding of What ‘Breakthrough’ Designation Means, Study Finds

Posted 12 April 2016 | By Zachary Brennan 

Physicians Lack Understanding of What ‘Breakthrough’ Designation Means, Study Finds

A US survey of board-certified internists and specialists revealed “substantial deficits in knowledge” of what it means for a drug to be approved by the US Food and Drug Administration (FDA) and approved via the “breakthrough” pathway, according to a research letter published in JAMA on Tuesday.

Since 2012, FDA has designated certain drugs as "breakthrough” therapies (76 drugs have received the designation through April 2015) if preliminary clinical evidence – such as an improvement in a pharmacodynamic biomarker – suggests an advantage over existing treatments. 

And although this term “breakthrough” oftenleads consumers to be overly optimistic about a drug’s  effectiveness, Aaron S. Kesselheim, M.D., J.D., M.P.H., of Brigham and Women's Hospital, Boston, and colleagues sought to understand more about how physicians understand the term “breakthrough” means and what FDA approval of such a drug means.


The survey of nearly 700 physicians asked three questions about FDA approval and five on breakthrough therapies. Physicians also chose between prescribing two new, identical hypothetical drugs, both of which met the statutory definition of breakthrough therapy but only one was called a “breakthrough” drug.

Physicians also were randomized by computer to read one of four versions of a mock FDA press release about a hypothetical new drug for lung cancer, approved based on tumor shrinkage: (1) the “facts alone” version described FDA approval data, (2) the “breakthrough” version stated that the FDA “designated it as a breakthrough drug,” (3) the “breakthrough/expedited” version added the drug’s review speed, and (4) the “breakthrough/warning” version warned that the drug’s effect on survival was unknown.


Respondents showed limited knowledge of FDA approval: 73% incorrectly believed FDA approval means comparable effectiveness to other approved drugs, while 70% incorrectly believed approval requires both a statistically significant and clinically important effect.

And for the three breakthrough questions, 52% incorrectly believed that randomized trials are needed to earn a breakthrough designation. Physicians also preferred the breakthrough drug Axabex (94% [95% CI, 91%-95%]) over the other drug, Zykanta, which had no breakthrough designation (6% [95% CI, 5%-9%]).

Kesselheim and colleagues wrote that although the results “are limited by social desirability and other inherent survey response biases and may not be generalizable beyond internists and medical specialists,” the misconceptions identified may show that physicians overprescribe newly approved drugs – particularly breakthrough therapies – and inadequately communicate how well these drugs work for patients who will use them.

The survey comes as a paper published in The Pharmacogenomics Journal in March also found that cancer drugs with breakthrough tags are developed more quickly than non-breakthrough products and they also see faster approval times than non-breakthrough products.

JAMA Research Letter

Categories: Regulatory News

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