Bioethicists have long known about a potential regulatory loophole that excludes certain types of clinical trials from federal regulations designed to protect the safety of human research subjects in the US. However, the number of clinical trials that fell into this gap remained unknown. Now, a letter published online today in the Journal of the American Medical Association reveals just how many trials may fall outside federal government supervision at present.
In the US, two federal policies provide oversight for research involving people. One is the so-called Common Rule, which applies to the majority of human studies that are performed or funded by the federal government. The other is the set of regulations issued by the US Food and Drug Administration (FDA) that apply to human tests of drugs, devices and biological products such as vaccines regardless of funding source. Some clinical trials are subject to only one of these regulations; others are governed by both. However, some privately funded trials are neither subject to oversight by the FDA nor the Common Rule.
A team led by Deborah Zarin, director of the site ClinicalTrials.gov—a federal registry of publicly and privately funded human trials—decided to find out just how many active trials fall into each of the various categories of oversight. The researchers compiled a list of some 24,000 US-based clinical trials that were listed as active in that database as of 13 September 2013, and estimated that at least 19% of the sampled trials were covered by both policies. Furthermore, between 1,285 and 3,696 trials, or approximately 5%–16%, were not subject to the Common Rule or the FDA, because they weren’t federally funded and didn’t involve drugs, devices or biologics. “That might include things like surgical interventions,” Zarin says.
The unregulated trials raise concerns for human safety, says Robert Califf, vice chancellor for clinical research at Duke University in Durham, North Carolina. “Put yourself in the shoes of a person that volunteers for a study,” he says. “I think most people would agree it would be good to make sure that there’s an encompassing system so you can be assured that the institution that’s conducting the trial has agreed to a common set of rules about how human studies should be done.”
At the same time that Zarin voices concern about studies falling outside the regulatory domain of both the FDA and Common Rule, she says it’s not ideal for trials to be subject to oversight by both rules. This double oversight, according to Zarin, could create a potential burden to researchers due to differences in reporting requirements and extra paperwork: “When people consider possible changes to the regulatory framework, these are the kinds of things that should be thought about.”