Expedited Approval Pathways Associated With Increased Safety-Related Label Changes, Study Finds

Regulatory NewsRegulatory News
| 08 September 2017 | By Zachary Brennan 

The US Food and Drug Administration (FDA) is increasingly granting faster reviews via expedited regulatory pathways, but a new article published in the British Medical Journal found a higher association with these expedited pathways and the likelihood of safety-related labeling changes than with non-expedited pathways.

In their analysis of 15 years of data, authors Sana Mostaghim, Joshua Gagne and Aaron Kesselheim of the Program on Regulation, Therapeutics, And Law (PORTAL) at Brigham and Women’s Hospital and Harvard Medical School found that drugs that won faster approvals had a 38% higher rate of safety-related label changes than drugs approved through non-expedited pathways.

"Further research is required to understand the underlying process factors contributing to the differential rates in safety changes that were observed in this analysis," the authors added. "Policymakers will likely need to ensure that these pathways are not overused, that there is sufficiently close post-approval monitoring of drugs approved through these pathways, and that patients and physicians are fully informed of the risks that accompany the widespread use of expedited development and regulatory review pathways in the approval of new drugs."

With the 21st Century Cures legislation in the process of being implemented, it’s expected that more treatments will see expedited approvals, particularly regenerative medicines.

The authors note that the increase in safety label changes points to the importance tracking drugs approved through expedited pathways "to help identify any emerging problems necessitating a safety related label change as early as possible," the authors write.

And although drugs that earn accelerated approval generally include a statement about the "clinical benefit . . . has not been established" because of "the reliance on an incompletely validated surrogate measure," the authors suggest that there "should also be formal requirements for manufacturers to alert patients about the higher rate of subsequent safety labeling changes arising from drugs approved through the accelerated approval, fast track, or priority review pathways." 

The authors also note several limitations to their research, including that the rate of safety changes "does not provide a qualitative assessment of the clinical relevance of a particular change.

"For example, the addition of ‘risk of serious cardiovascular events’ to the boxed warning of a label in which there was already some cardiovascular outcomes mentioned may have less clinical impact than the addition of new psychiatric side effects that were not previously included in that section of the label," they write. "Such qualitative analysis of the label changes is complicated by the fact that in some cases FDA only indicates that a change was made but then presents the whole label section, and in others it underlines or italicizes the text but does not indicate what was changed. Greater clarity from the FDA about the exact nature of each label change and the number of changes each month would be useful in resolving these issues."



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