Doing a Medical Device Clinical Trial?....Know Your Device's Risk Significance

When submitting your medical device clinical trial documents to an Institutional Review Board (IRB), you must know if your device is considered Significant Risk (SR) or Non-Significant Risk (NSR).

Significant Risk (SR) devices pose potential for serious risk to the health, safety, or welfare of a subject

Non-Significant Risk (NSR) devices are defined as those not being categorized as significant risk (SR)


This determination is important:
SR devices require both IRB and FDA approval before starting a clinical trial
NSR devices require only IRB approval before starting a clinical trial

Yes, that's right that you can initiate a medical device clinical trial without notifying the FDA if your medical device is a Non-Significant Risk device and you obtain IRB approval for your study.  That's a big difference from pharma studies where all drugs are considered high risk and require FDA approval before beginning a drug clinical trial.

So what defines an SR device?...

Under US regulation 21 CFR 812.3(m), an SR device means an investigational device that:

• Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;
• Is purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;
• Is for a use of substantial importance 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.

The definition of NSR is by default.  Your device is Non-Significant Risk (NSR) if your device does not meet the above definition for an SR device.

But who makes the final decision on SR versus NSR categorization?

Your Institutional Review Board (IRB) does (21 CFR 812.66)

If you want to start a clinical trial and you feel that your device does not pose a significant risk to study subjects:

• You (the Sponsor) submit your clinical trial documents (e.g., protocol, device description, Informed Consent Form, etc.) to your IRB along with a statement of why your device trial does not pose a significant risk to study subjects

• If the IRB agrees that the clinical trial does not pose a significant risk and determines the trial device as an NSR, then, no FDA approval is needed before you start the trial. Your clinical trial can start under AbbreviatedInvestigational Device Exemption(Abbreviated IDE) requirements.

• If the IRB disagrees and they deem your trial to pose a significant risk, then your device is deemed SR and you must submit an Investigational Device Exemption (IDE) application to FDA for approval before starting your trial.

So if you are planning to start a medical device clinical trial, you need to know your risk significance (SR or NSR).  Note that this is different from your risk classification, which in the US, medical devices are also classified according to their risk (Class I devices are lowest risk; Class II devices are medium risk; Class III devices are highest risk).

It can be confusing to know how to distinguish risk classification from risk significance, but think of it this way:

• your medical device's risk classification is determined by the FDA according to your device's level of risk (Class I, II, or III) regardless of whether you are planning a clinical trial or not.
• when initiating a clinical trial, your IRB will assess the device's risk significance (SR or NSR) and that will determine if you need to go to the FDA and apply for an Investigational Device Exemption (IDE) before you can receive IRB approval for your clinical trial. If your IRB deems your device to be SR, then you will need to apply for an IDE from the FDA (got to love all those acronyms).