The Food and Drug Administration (FDA) has historically approved powerful and addictive drugs based on nominal clinical trials of certain patient populations, according to a new study published in the Annals of Internal Medicine.  The study found between 1997 and 2018 the FDA approved drugs for chronic pain lacked trials lasting longer than three months and excluded patients who could not tolerate the painkillers.  It analyzed the late-stage clinical trial data and pooled multiple analyses for 48 opioids approved by the FDA, nine of which were for acute pain and 39 of which were for chronic pain.  What’s more, the trials failed to analyze known risks, including drug diversion risk and non-medical use of the products.  The end use of these addictive drugs was not taken into consideration.The researchers found that of the “39 approved treatments, only 21 were supported by at least one pivotal trial and these trials had a median length of 84 days.”  They also documented that “four-fifths of the opioids were approved on the basis of study designs that excluded patients who could not tolerate the drugs, experienced side effects early, or reported few immediate benefits.”

Photo by Pawel Czerwinski on Unsplash

“Our study shows that there are evidence gaps that the FDA needs to address in approving new opioids,” said Thomas Moore, a study co-author and senior scientist at the Institute for Safe Medicine Practices.In 2018, more than 46,000 people in the U.S. died of an opioid overdose, including nearly 15,000 deaths involving a prescription opioid, the researchers found.  And, a separate government report also found that the mandated safety program the FDA rely on to minimize opioid abuse and misuse is not “well suited to quickly address the ongoing crisis across the U.S.,” due to a lack of coordination between drug makers and the FDA, making it difficult for the regulatory agency to  gain access to the data.The current study’s authors cited “long-term, around-the-clock use of opioids, as well as specific opioids…[including] the 2013 approval of Zohydro, an extended release form of hydrocodone, and the 2018 approval of Dsuvia, a tablet version of a decades-old intravenous painkiller that is up to 10 times more potent than the highly addictive fentanyl.”  The authors also state the FDA “has been lax for endorsing certain trial designs for proving effectiveness.  They pointed to enriched enrollment randomized withdrawal, designs, which exclude patients for whom a drug does not perform well in the ‘run-in period’ before patient randomization occurs.”  They noted that “17 out of 21 trials, or 81%, were set up according to this type of design.  For pivotal trials, this worked out to a median of 37.2% in which the initially enrolled patient samples were excluded.”Moore said, “This is a large number.  Any drug looks more effective if you get to exclude the patients who are not doing well.”  The trials seem to favor drug companies and be designed to advance the approval process without hindrance rather than adequately determine the risks of use.

Sources:

For two decades, the FDA approval process for opioids had numerous shortcomings, study findsKey Evidence Supporting Prescription Opioids Approved by the U.S. Food and Drug Administration, 1997 to 2018For two decades, the FDA approval process for opioids had numerous shortcomings, study finds