IDE compliance is a threefold process

Tips for adhering to regulations

Clinical trial managers and investigators may need to brush up on the regulations regarding investigational device exemption (IDE) since researchers and research staff often forget about the three major categories of compliance regulations, an expert advises.

The three requirements are the IRB requirement, the informed consent requirement, and the FDA’s IDE regulations, says Jeffrey Gibbs, director of Hyman, Phelps & McNamara in Washington, DC. The firm specializes in FDA legal and regulatory issues, and Gibbs has spoken at national conferences on IDEs.

"Some investigators don’t understand what’s entailed in following those regulations," he says. "There’s a lack of knowledge, and the regulations are not self-explanatory, and some don’t have the procedures or staff and resources to deal with it."

The first thing clinical trials staff need to know is that the regulations apply to clinical studies with devices in the United States, and there are three levels of studies, including these:

  • The first level involves studies where the sponsor needs to obtain FDA approval for the IDE before the study can begin. "Those are devices that present significant risk," Gibbs says.
  • The second level are for devices that are subject to IDE regulations in part, but not for the entire IDE regulations. "Those are the ones where the IRB has determined the study presents nonsignificant risk," he says. "The risks are sufficiently low that they don’t need IRB review."
  • The third level are for studies involving in vitro diagnostics. "Typically, these are to take a blood specimen," Gibbs says. "This could be for a study in which you take a blood specimen to see if human growth hormone levels are the same with the new and old test, so there’s no risk."

It’s important to understand the implications for having a study in one of the three categories. He describes these as follows:

  • Significant risk: These studies are subject to all IDE requirements, and everything applies, Gibbs says. "The requirements would involve monitoring patients, following the protocol, and accurately transcribing study records. There are a lot of details and, in general, these studies are more likely to be audited."
  • Nonsignificant risk: "These studies are less likely to be audited by the FDA," Gibbs says. "It’s not that they’re exempt, but they’re less likely because they’re not for pre-market approval studies, and these could be for more routine products, such as a new dental product, for example."
  • No risk: The primary issues with these types of studies are the informed consent and IRB approval for exempt studies, he says.

"The FDA expects the same level of data accuracy," Gibbs says. "These studies may be ones where the patients aren’t known to the investigator; they’re anonymous: someone collects a blood specimen, and you don’t know whose specimen it is."

In those cases there may be no informed consent, he adds."So it can be an issue of wanting to know the underlying consistency of records, and if you can’t link it back to a patient that can be a problem," Gibbs notes. "Suppose the patient had multiple sclerosis [MS], but if you don’t know who the patient is, how do you prove the patient had MS?"

This category, like the significant risk category, may be used for pre-market approval products, he says. "Pre-market approval could apply to the nonsignificant risk category, but it’s less likely."

In general, the class I devices with lower risk are less likely to require a pre-market approval, Gibbs says.

Investigators need to know whether a study will need pre-market approval and whether it is an exempt study, and if it’s a pre-market approval study there’s a much greater likelihood the study will be audited, he notes.

"These are studies that go on the market without needing any clearance," Gibbs says. "Someone might ask you to do a study for labeling or promotional purposes, but not to get FDA approval."

If the study is for marketing claims and needs no FDA approval, then it may not need to go through IRB review, he adds.

"You could have something that’s exempt with the same indication that the product has been cleared, but if you’re studying it for an off-label use then you may need IRB and FDA exemption," Gibbs says.

For example, suppose the product is an orthopedic screw that is already on the market for certain uses. If a doctor has studied it with support from the sponsor, then it doesn’t need to go to an IRB to get additional data on its approved use, he explains.

However, if the screw is used to prevent a life-threatening disease, in an extreme example, then it’s the same product with a new use and it will need IRB approval, informed consent, and FDA approval of the IDE, Gibbs explains. "It’s much more complicated for devices than for drugs."

If clinical trials don’t follow the rules, then the FDA might cite the study or send a warning letter, he adds.

"The worst is if they altered data or repeated mistakes, then the sanctions get much more serious," Gibbs says. "If it’s just an accident, then there’s a warning letter."

Typically, IDE violation warnings require adequate documentation, Gibbs says. "The FDA wants to see that things are documented and that documents are consistent."

Some examples of mistakes include:

  • A case report form shows that transcribed information is consistent with the underlying source documentation.
  • A radiographic report says one thing, and the case report form says something different, or the protocol form says the follow-up X-ray is plus or minus one week, and they do it in four months instead, Gibbs says.

"I think that part of it is that investigators are used to being doctors treating patients, and they don’t have the same flexibility as investigators," he says. "When you’re a doctor, you do pretty much what you want, and it’s different once you are an investigator: you’re inhibited and follow rules laid out in the protocol, following the FDA’s rules."

The take-home message is to attend carefully to documentation and to fix problems once they’re identified, documenting how they were resolved, Gibbs says. "A lot of times there’s a tendency to say, We’re doing a great job — nobody’s been hurt, or to not act with a great deal of alarm when problems come up or if the staff don’t do what they’re supposed to do," he says. "But you have to take corrective action because the test is not whether someone’s been hurt; the test is whether there is a deviation from the requirements."

Put routine policies in place and follow these, Gibbs advises. "If someone is trying hard to make changes, and there’s a clear effort to address things to make a big difference, then it’s much easier if you can say, We have policies in place, but someone didn’t follow them, and we’ve now reinforced the policies,’ than to say, We never thought of that happening,’" he adds.

Clinical trial managers who’d like to take a look at the sort of violations that routinely appear with studies should check the FDA’s web site in the IDE area for the warning letters that are issued on a weekly basis, Gibbs notes. "I look at the warning letters each week as they come out."