Pamela A. Popper, Ph.D., N.D.

Wellness Forum Health

Since 2012, The FDA has used the term “breakthrough therapy” to describe drugs that may have an advantage over existing treatments for changing biomarkers based on preliminary clinical evidence. This is one of several practices used to expedite drug development and approval for serious or life-threatening conditions. As of April, 2015, the FDA has designated 76 drugs as “breakthroughs.”  The problem is that doctors do not understand what the term means and instead most of them believe that it means the drugs are supported by significantly more evidence than actually is the case.

A recent survey of 692 doctors highlights the misunderstanding. When presented with two identical hypothetical drugs, 9 out of 10 doctors chose one over the other based solely on the “breakthrough” designation. Both drugs had similar side effects, were to be taken on the same schedule, and were equally covered by the patients’ insurance.  Additionally, 52% of the doctors thought that strong evidence from randomized trials was necessary in order to earn the “breakthrough” label.

The survey also showed that doctors have limited knowledge of what FDA approval in general means. 73% of the docs believed that FDA approval meant comparable effectiveness to other approved drugs, 70% believed that approval required a drug have a statistically significant and clinically important effect.[i] Neither of these statements is true.

In fact, according to a 2014 analysis published in JAMA, more than one third of drugs are approved based on a single trial, without replication. Researchers reported that most trials are small, short, and focused on surrogate markers, rather than important endpoints like death. The group expressed concern over the lack of uniformity the FDA used to evaluate evidence and concluded, “……….. Based on our study of the data, we cannot be certain that this expectation (FDA approval certifies safety and efficacy) is necessarily justified, given the quantity and quality of variability we saw in the drug approval process.”[ii]

These facts highlight the importance of consumer education; consumers just cannot trust that their doctors know best.

[i] Kesselheim A, Woloshin S, Eddings W, Franklin J, Ross K, Schwartz L. “Physicians’ Knowledge About FDA Approval Standards and Perceptions of the “Breakthrough Therapy” Designation.” 1Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Boston, Massachusetts
2Center for Medicine and the Media, Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire
3Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
4American Board of Internal Medicine, Philadelphia, Pennsylvania JAMA. 2016;315(14):1516-1518.

[ii] Downing N, Aminawung J, Shah N, Krumholz H, Ross J. “Clinical Trial Evidence Supporting FDA Approval of Novel Therapeutic Agents, 2005-2012.” JAMA. 2014;311(4):368-377