Dissecting the Patient Perception of FDA's Breakthrough Designation

A research letter published in the current issue of JAMA Internal Medicine has found that the terms “breakthrough” and “promising” raised people’s expectations on the drug’s performance as opposed to when the drugs were described as having met the breakthrough criteria.

The authors write that all announcements by the FDA on the approval of breakthrough-designated drugs use the word “breakthrough” and almost half use the term “promising.” These news releases by the FDA are readily accessible to patients and the absence of a specific descriptor for these terms could lead to an unwarranted increase in the patient’s confidence in the data.

For their clinical study, the authors recruited 597 online participants from the United States, with a mean age of 36 years (range 19 years to 83 years). Of these, 41% were women and 55% had a college and/or a graduate degree. Participants were randomized to 1 of 5 vignettes:

• facts-only, which described the drug as meeting the breakthrough criteria without using the term
• the word promising added to the description
• the word breakthrough added to the description
• tentative explanation, which used FDA-required labeling language
• definitive explanation, which changed the wording from “may be contingent” to “is contingent.”

This was based on an FDA release for a metastatic lung cancer breakthrough drug that was conditionally approved based on a surrogate outcome of tumor shrinkage.

The study found that adding either “promising” or “breakthrough” significantly increased the number of participants rating the drug as “very” or “completely effective” to 23% and 25% respectively, compared with 11% in the controls. Inclusion of the terms also increased the number of those who believed the supporting evidence as being “strong” or “extremely strong,” from 43% of controls to 59% (promising) and 63% (breakthrough). Adding the explanations, though, reduced the percentage of respondents who wrongly believed that the drug had been proven to save lives, the authors write. When participants were asked which of 2 drugs would they take for a potentially deadly condition, the “breakthrough” or the one meeting the breakthrough criteria, an overwhelming 92% chose the “breakthrough” drug.