Ethicists warn that the drug approval process does not go far enough
Companies should be required to show a drug's actual promise earlier, they argue
President Donald Trump promised to cut "the red tape" at the FDA
The process governing clinical drug trials should be strengthened to make them safer and much more effective, researchers argue, but they worry that the Trump administration will be going in a different direction.
In January 2016, an early-stage clinical trial of a painkiller in France went horribly wrong, leaving one previously healthy volunteer dead and sending five other volunteers to the hospital.
An investigation found that the conditions in which the trial was authorized by French authorities were within regulations, but drugmaker Bial and Biotrial, the company that ran the testing, were found to be at fault “on several counts,” including how much of the drug they gave volunteers. Communications failures were also found.
Outside experts concluded that Bial failed to submit adequate proof that the drug was needed and could work. Bial argued that the toxicities were not predictable and that it followed the usual human testing rules and norms.
It is those rules that Kimmelman and Federico take issue with in their commentary.
Currently, European and North American companies are required to submit data to their appropriate country’s regulators to move from lab and animal testing to testing drugs in humans. Regulators look at data to make sure the drug would be safe enough to test in humans. In this early stage, the company is not required to submit evidence that the drug would be effective.
Few clinical trials end up hurting healthy volunteers like the French trial did. There have been severe accidents in only two of 3,100 first-in-human trials overseen by the European Medicines Agency since 2005, according to a study. But many drugs still do not get approved because they do not demonstrate efficacy, and Kimmelman thinks a new system could improve the odds and lower the costs of creating new drugs.
“I’ve been doing this research about clinical trials for over a decade now, and when I first read that regulators don’t evaluate a drug for efficacy before a company can proceed, I just didn’t believe it at first,” he said. “But there is no regulation in place that adjudicates the clinical promise of a new drug when the data is submitted. It is up to the sponsor to determine that.”
The commentary argues that commercial interests can’t be trusted to make sure that testing goes ahead only “when the case for clinical potential is robust.”
“We believe that many (first-in-human) studies are launched on the basis of flimsy, underscrutinized evidence,” they write.
In the case of the fatal French trial, at least five drugs with similar designs had been tested in humans without any success, the commentary said. If companies were required to show a drug’s efficacy, that trial probably would not have gone forward.
Without having to show the promise of a particular drug, companies may be wasting time and valuable resources Kimmelman said. But more than half of all drugs that reach the later stages of drug testing fail, largely because they don’t demonstrate efficacy, earlier studies have shown.
If companies spent less time on drugs that may not be needed, Kimmelman said, there would be more time to work on the drugs that are.
“Scientists are a very scarce resource. It takes years and years of training to be able to run a trial, and we want to allocate that resource as judiciously as possible to lead to major advances and cures,” he said.
However, the system that is in place doesn’t “have the capacity to evaluate preclinical evidence,” Kimmelman said.
He believes regulators could create a centralized agency, ideally within the Food and Drug Administration, to help evaluate preclinical evidence. Since the data would include a lot of proprietary information, the committee could meet privately.
Based on the current political climate, he argues, this group is needed now more than ever.
“If President Trump follows through on some of the plans he has articulated on the campaign trail about drug approval, he plans to weaken the critical evidence needed to approve new drugs,” Kimmelman said.
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When campaigning, Trump said in October (PDF) that he would like to “speed the approval of life-saving medications” and promised that he would be “cutting the red tape at the FDA.”
“That means when drugs will be approved for use commercially, there may be no requirement at all for needing evidence of efficacy. So that puts the onus on preclinical work,” Kimmelman said.
The Society for Clinical Trials, an educational and scientific organization that works internationally to advocate the use of clinical trials and to promote best practices in drug trials, did not respond to a request for comment.