By Susan E. Matthews, Everyday Health Staff Writer
New research shows that drugs that are expedited for approval are tested on fewer patients and don't get proper follow-up research.
A new paper out in JAMA Internal Medicine questions whether FDA fast-tracking of drugs is safe for patients.
Researchers at the Institute for Safe Medication Practices in Horsham, Penn., and at Wake Forest School of Medicine looked at track records on the 40 percent of new drugs the FDA approved in 2008 that were fast-tracked. They found that fast-tracked drugs had been tested in fewer patients than drugs that went through the regular approval process, and that required post-approval follow-up studies still have not been conducted on many of the drugs.
“We’ve placed all this emphasis on approving drugs quickly,” said study author Thomas Moore, A.B., of the Institute for Safe Medication Practices. “The questions we left on the table get answered very slowly.”
The researchers analyzed all of the drugs the FDA approved in 2008. Of the 20 that were approved, 8 had been expedited to increase the speed of the process, which is done for particularly promising or novel drugs, or those for life-threatening diseases.
The drugs that were expedited that year were approved after only an average of 5.1 years of clinical development, with the shortest time to approval being 1.6 years and the longest 10.6 years. For drugs on a normal track, the average length of clinical development was 7.5 years, with the fastest being 4.7 years and the slowest coming in at 19.4. Additionally, the researchers found that expedited drugs had been tested only on a median 104 patients, while normal-track drugs had been tested
on a median 580 patients.
Reasons for Expediting Drug Approvals
The FDA expedites drugs “in situations of serious and life-threatening diseases with unmet medical need,” according to Tara Goodin, a spokeswoman for the FDA. “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,” Goodin wrote in an email. These examples include diseases as unknown as HIV/AIDS was in the 1980s, or deadly, fast acting cancers with no foreseeable cure.
Additionally, drugs focused on certain diseases may also have a smaller pool of patients to draw from for tests, Goodin added.
Furthermore, for expedited drugs, the FDA required 85 post-market commitments, in the form of follow-up studies on the drugs’ success and safety. By the time the new study was underway, in 2013, only 26 of those post-marketing studies had been completed; an additional eight had been submitted to the FDA and are under review.
In an accompanying commentary in JAMA Internal Medicine, David Carpenter, PhD, a government professor who specializes in health regulation Harvard University, pointed out that according to his own research, he found that it takes an average of 11 years for post-market safety information to appear on prescribing information, emphasizing the problem of slow post-market reviews on approved drugs.
Goodin responded to the claim that post-market review happens slowly by stating that, according to the Wake Forest researchers' own numbers, “40 percent of the studies have been completed.” Furthermore, Goodin noted, 71 percent of the studies expected to be completed by 2013 had been either fully completed or submitted for review.
As to why 29 percent of the studies expected to be completed by 2013 had not been done, Goodin wrote that “agreement on final protocol, recruitment and training of investigators, and recruitment of patients” can contribute to delays.
Carpenter said that though he hadn’t seen the data to back up the FDA’s numbers, a 2013 study had found that “nearly half of the commitments agreed to in a single calendar year hadn’t even been started yet.” The FDA faces enormous time pressure to get drugs on the market, but once they’re on the market, the time pressures evaporate. “They need to mandate deadlines that are as stringent for getting a drug tested post-market as they are for getting a drug approved," he said.
The lag in post-marketing studies is particularly concerning when you consider their importance in assessing safety and efficacy in the general population. For example, the FDA approved a powerful opioid, Zohydro, last week that is not formulated to protect against addiction -- that is, formulated so it's impossible to crush up.
"I am counting on the FDA to perform rigorous post-marketing studies and analysis to ensure this drug doesn't create another new wave of addiction," U.S. Rep. Harold "Hal" Rogers (R-Ky.) wrote in a statement to MedPage Today in response to the approval.
What’s Best for Public Health?
The Wake Forest study made clear that drugs approved under expedited pathways do in fact reach the market sooner, said Caleb Alexander, MD, MS, co-director of the Center for Drug Safety and Effectiveness at the Johns Hopkins Bloomberg School of Public Health. The fundamental question that society needs to answer in response to these results is whether the process is successful, he said.
“Are we striking the right balance between access to innovation and public health?” Dr. Alexander asked.
The study shows that the amount of FDA testing is “often very modest,” which Moore said doesn’t surprise him, but is troubling. “It doesn’t help if you don’t know how to use it wisely and you’re not sure the drug has benefits clinically,” Moore said of expedited approval, adding that this often makes it more difficult to understand long- or short-term benefits and risks.
Carpenter wrote that there are continued lobbying efforts to broaden the rules that allow drugs to be expedited. But this could result in lowering the barrier of evidence for all pharmaceuticals, he argued.
“In the absence of sound, independent evidence and underlying trust, just about everything can go wrong,” Carpenter wrote.
Ask Your Doctor: Was My Drug on the Fast Track?
Consumers should ask their doctors about the approval process for drugs they’re prescribed, and research drugs themselves if their doctors are unsure how a drug was approved, Moore said. “It’s almost as easy for a poorly tested drug to hurt them as it is for the drug to help them,” he said.
When asked if the FDA notifies patients who are receiving newly approved drugs that went through an expedited process, Goodin replied that the organization was “not aware of a formal notification process,” and suggested patients check the FDA.gov website for information.
Carpenter said he thought it would be possible to include a physician warning that doctors could pass on to patients, explaining that the drug had been expedited because of its promise or the deadliness of disease, but that researchers don’t know as much about it as they do about other drugs.
“The news here for consumers is all drugs have risks,” Alexander said, but “drugs that have been on the market for longer have a greater chance of being scrutinized.”
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