1. Rosenberg, Karen


According to this study:


* Several steps can be taken to improve the amount and quality of the safety and efficacy data used in support of new drug applications for opioid analgesics.



Article Content

The ongoing opioid epidemic has prompted scrutiny of the regulatory activities of the U.S. Food and Drug Administration (FDA). Continuing debates about FDA decisions, stretching back to the agency's approval of OxyContin (oxycodone) in 1996, led researchers to analyze the clinical trial and safety data submitted by pharmaceutical companies to gain FDA approval of prescription opioid analgesics from 1997 to 2018.


During the study period, the FDA approved 48 new drug applications (NDAs) for opioid analgesics. Of these, only one was for new molecular entities; the others were for new dosage forms, new combination products, new formulations, or products previously marketed with no NDA.


Of 39 NDAs for chronic pain, 21 were supported by one or more pivotal trials (that is, phase 3 efficacy trials), with a total of 28 pivotal trials performed. The median duration of the 28 trials was 84 days, and a median of 299 patients were enrolled. Seventeen chronic pain NDAs used trials with an enriched enrollment study design, in which patients who can't tolerate or don't respond well to the drug or have adverse effects are excluded.


Of the nine NDAs for acute pain, eight were supported by at least one pivotal trial, with 19 pivotal trials performed. The median duration of these trials was one day, and a median of 329 patients were enrolled.


A safety review was included in 29 of the 39 approved NDAs for chronic pain indications. Fifteen of these NDAs monitored drug tolerance; eight assessed diversion of the study drug; seven measured aberrant use of the drug; and five reported measurement of opioid overdose symptoms.


The authors note that their analysis was limited to pivotal trials and pooled safety analyses of NDAs for chronic pain, and only one NDA was for a new moiety. They make several recommendations for improvements the FDA can make to optimize the efficacy and safety data used in support of new opioid approvals, helping to ensure more informed prescribing and a reduction in the public health risks posed by opioid analgesics.


Heyward J, et al Ann Intern Med 2020 Sep 29. Online ahead of print.