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“Significant Risk” and “Nonsignificant Risk” Determinations for Medical Devices

October 31st, 2017 by Robert Romanchuk, IRB Vice Chair

In medical device research, the determination of “significant risk” or “nonsignificant risk” can sometimes be confusing, especially for those new to device research. Unique to the device space, this risk determination is not the same as a “no more than minimal risk” determination.

Let’s take a closer look at what significant risk (SR) and nonsignificant risk (NSR) determinations mean for medical device clinical trials.

Definitions

Here’s a quick look at the definitions provided in FDA’s Information Sheet on significant risk and nonsignificant medical device studies. If you’re not familiar with this document, and work in this space, I strongly suggest you give it a read for more detailed information on these risk determinations and their implications.

An SR device study involves an investigational device that either:

  • Is intended as an implant and presents a potential for serious risk to the health, safety or welfare of a research subject;
  • Is meant to be used to support or sustain human life and presents a potential for serious risk to the health, safety or welfare of a subject;
  • Plays an important role in diagnosing, curing, mitigating or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety or welfare of a subject;

OR

  • Otherwise presents a potential for serious risk to the health safety or welfare of a subject.

Conversely, an NSR device study is one that does not meet the above definition.

You’ll notice that each option in the SR definition mentions “a potential for serious risk to the health, safety or welfare of a subject.” If the investigational device meets one of these criteria and is deemed SR, it is likely that the device will require an Investigational Device Exemption (IDE) for the study to commence.

It’s possible that a study can be determined SR even when the device under investigation was previously determined NSR. An approved laser may operate at more than one frequency according to clinical setting, so some frequencies may be SR while others are NSR. Another example is a scope and/or other device that may be used in a more invasive clinical setting than originally approved, which makes the device higher risk. The determination is based on how the device will be used in a particular study, not on the device alone.

SR/NSR Determinations Are Not Minimal Risk Determinations

Understandably, the SR/NSR risk determination is often confused with “no more than minimal risk” determinations. A “minimal risk” study means the research involves no greater than minimal risk to study subjects (i.e., the level of risk an average healthy person would expect to encounter during typical daily experiences), and it can be reviewed via expedited review, conducted by a designated IRB member rather than the fully convened IRB. SR/NSR and minimal risk are separate determinations. Just because a device study has been determined NSR does not mean that the study would be considered minimal risk.

The Study Has Been Determined “Significant Risk”—Now What?

The key differences between SR and NSR studies are found in the investigational device exemption (IDE) approval process and in the sponsor’s reporting and record keeping requirements.

More oversight and reporting are required for SR device studies, since they are riskier by definition. The study sponsor must submit an IDE application and receive FDA’s approval of the study. An IRB may review an SR study while FDA is reviewing the IDE application, but the study cannot begin until the agency approves the IDE. The IDE brings with it additional responsibilities with which researchers must comply; for more information, check out FDA’s Device Advice section on IDE responsibilities (IDE responsibilities can be found at 21 CFR 812.40 and subsequent parts of Subpart C).

Since NSR device studies are inherently less risky than SR studies, there are abbreviated requirements (found at 21 CFR 812.2[b]); IRB review is deemed to be the IDE approval, and no FDA IDE determination is required; the IRB’s study approval doesn’t need to be reported to FDA; and progress reports and final reports to FDA are not required.

Making the Determination

The study’s sponsor is responsible for proposing the initial risk determination. The sponsor will submit this proposal to the IRB for consideration. FDA is also available to help make the determination, and in some cases it’s possible that FDA has already made the risk determination before the study reaches the IRB—in these cases, the FDA’s determination is final.

If FDA hasn’t already made the risk determination, then it’s up to the IRB to decide whether it concurs with the sponsor’s risk assessment. The IRB may disagree with the sponsor’s assessment. Here are some key items the IRB will consider:

  • The basis for the risk determination
  • The type of harm that may result from use of the device
  • Any additional procedures a study subject may need to undergo as part of the study (the IRB must assess the potential harm of the procedure as well as of the device itself)

It is possible for the IRB to approve the study with the condition that the study may not commence until an IDE has been provided by the FDA.

Need more information on device research? Read our blog Hotspots and Challenges in Medical Device Research, or review our Device Resources.