The expedited review and approval of new drugs by the Food and Drug Administration may have exposed some patients to substantial safety risks, according to a study published in JAMA Internal Medicine.
The study analyzed 20 new drugs that were approved by the FDA in 2008 – including Johnson & Johnson’s opioid pain medicine Nucynta (tapentadol). Eight drugs were given expedited review and 12 had a standard review.
The researchers found that expedited drugs underwent an average of just over 5 years of clinical testing before being approved, compared to 7.5 years for those that had a standard review.
Perhaps more importantly, the number of people tested during clinical trials was substantially different: during expedited reviews a median of 626 patients were exposed to a drug, compared to 2,133 in a standard review.
“The study shows that new drugs – especially novel drugs – are developed and approved quickly, but that testing is modest and many safety questions are left unanswered for years,” study co-author Thomas Moore of the Institute for Safe Medication Practices told Pharmalot.
“The testing of new drugs has shifted from a situation in which most testing was conducted prior to initial approval to a situation in which many innovative drugs are more rapidly approved after a small trial in a narrower patient population, with extensive additional testing conducted after approval,” wrote Moore and co-author Curt Furberg, a professor at Wake Forest School of Medicine.
In many cases, the additional testing was never done. For the 20 new drugs approved in 2008, the FDA required 85 follow-up safety trials. By January, 2013, only 40% of those studies had been completed.
The expedited review process was implemented by the FDA after pharmaceutical companies, lobbyists and medical associations urged the agency to speed up the approval process so that promising new drugs could reach patients sooner. Critics warned the FDA was approving drugs before they were fully tested.
Since the 20 new drugs were approved in 2008, Moore and Furberg found that “substantial additional risks” were found in 7 of them.
“As many safety questions were not answered prior to drug approval, some patients may have been exposed to safety risks that had not been well characterized,” they said.
But even when given a standard review, safety issues arose once a new drug was on the market. One such drug, Johnson & Johnson’s painkiller Nucynta (tapentadol) had the most new risks of the 20 drugs approved in 2008; with 4 items in a new Boxed Warning, 3 new contradictions and one more restricted indication.
Nucynta, a Schedule II controlled drug, was originally approved for the treatment of moderate to severe acute pain. In 2011, an extended-release formulation (Nucynta ER) was approved for the treatment of moderate to severe chronic pain. Nucynta is often prescribed for the treatment of diabetic neuropathy.
Asked to comment on its review process, the FDA said in a statement that “the expedited development programs are working as intended by getting promising new drugs to patients more quickly.”
“In situations of serious and life-threatening diseases with unmet medical need, patients and physicians who treat them have told us repeatedly that they are willing to accept greater uncertainty about risk in order to have access to the hope of improved treatment today.”
The FDA also said it had a “robust program for postmarketing surveillance.”
But in an accompanying editorial, Daniel Carpenter, a professor of government at Harvard University, was sharply critical of the FDA’s review process, calling it “growing hodgepodge of exceptions to the rule of rigorous premarket review.”
Carpenter also warned that further efforts by the Obama administration to speed up the review process could backfire and destroy public trust in the health care system.
“If regulation fails and physicians and the public do not have evidence based trust in drugs, fewer drugs are prescribed, patients do not receive therapies that might help them, investment drops accordingly, and the social foundations of the health system are weakened, “ Carpenter wrote.
“In the absence of sound, independent evidence and underlying trust, just about everything can go wrong.”