Background and Definitions

FDA regulations governing human research state that, for studies involving use of an investigational device, the investigator (or sponsor) must obtain either a "significant risk"  Investigational Device Exemption (IDE) from the FDA, or a "non-significant risk" IDE from an Institutional Review Board (IRB).  The FDA document titled, “Significant Risk and Nonsignificant Risk Medical Device Studies (January 2006)” provides guidance for investigators and IRBs to use in making these decisions.  The following information is excerpted from this document.

The FDA defines a significant risk (SR) device as one that presents potential for serious risk to the health, safety, or welfare of a subject; and

•        is an implant,

•        is used in supporting or sustaining human life,

•        is of substantial importance in diagnosing, curing, mitigating or treating disease, or

•        otherwise prevents impairment of human health.

Examples of SR devices include: surgical lasers, urological stents, contraception devices and CPR devices. For a comprehensive list of SR device examples Click Here. 

A non-significant risk (NSR) device is one that does not pose significant risk.  NSR devices may be approved by an IRB without applying for to the FDA for an IDE. 

Examples of NSR devices include: daily wear contact lenses, non-medicated wound dressings, conventional gastroenterology endoscopes and short-term use foley catheters. For a comprehensive list of NSR device examples Click Here. 

In most cases, the sponsor will be the device manufacturer or company seeking marketing approval for the device.  However, in some cases the investigator may also be the sponsor. 

Determining whether a Device is SR or NSR*

The IRB does not need to make the SR or NSR determination if FDA has already made the risk determination.  Most often, clinical investigators submit SR device investigations for IRB review after the sponsor has already received the IDE approval from FDA.  The IRB may ensure that SR device investigations have an FDA-approved IDE by asking the PI to provide, or request from the sponsor, a copy of FDA’s IDE approval letter. 

In some cases, the investigator or sponsor will make an initial assessment that a device presents a non-significant risk and will ask an IRB to uphold that determination.  In the event another IRB has made a previous determination of non-significant risk, the UT Southwestern IRB must make an independent SR/NSR decision.

If the investigator or sponsor believes a device poses a non-significant risk, the IRB will make a formal determination after reviewing the NR1 and other application materials.  The IRB submission documents should include:

•        a description of the device,

•        reports of prior investigations with the device,

•        the proposed investigational plan,

•        subject selection criteria, and

•        an explanation of why the device is believed to be of non-significant risk.  The IRB should also be informed if the FDA or any other IRB has determined the device to present a significant or non-significant risk, and provide any further information requested by the IRB.

*Note: The SR/NSR criteria are different than the “minimal risk” and “greater than minimal risk” criteria for human subject research.

IRB Review

When reviewing a device trial, the IRB must make two separate decisions, based on different criteria.  

First: Does the device present significant or non-significant risk? (A NSR device study may start as soon as the IRB reviews and approves the study and without prior approval by FDA.  SR devices require an IDE from the FDA before the study can begin). 

Second: Is the study approvable or not?

The IRB should consider the following in determining whether a device poses a SR or SNR:

•        the principal investigator’s or sponsor’s description of why the device is not SR;

•        whether the proposed NSR research study meets the definition of “significant risk;” and

•        the risks of the proposed use of the device.

Note:  The UT Southwestern IRB will likely refer to the FDA for risk determinations on use of “novel” devices, devices where the UT Southwestern IRB lacks sufficient expertise to adequately evaluate the device, or in situations where there may be a real or perceived institutional conflict of interest.

To determine if a device involves a significant risk, the IRB must consider the nature of the harm that may result from use of the device.  If a device being investigated might cause significant harm to any of the subjects, the device should be considered "significant risk."  Also, if the subject must undergo a procedure as part of the study (e.g., a surgical procedure to implant or explant the device), the IRB must consider the potential harm caused by the procedure(s) as well as the potential harm caused by the device.  Devices for which the potential harm to subjects could be life-threatening, could result in permanent impairment of a body function or permanent damage to body structure, or could necessitate medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to body structure, are included among those devices that present significant risk.  The determination of significant risk depends on the use of the device in the particular study as well as the inherent risks of the device itself.  Several examples follow:

            The study of a change to a commercially-available pacemaker (e.g., new leads, battery pack, or software) poses a significant risk because the device is used to support or sustain human life and it presents a potential for serious harm to the subjects.  This is true even though the changed pacemaker may potentially pose less risk, or only slightly greater risk, in comparison to the commercially available model.

            The study of an extended-wear contact lens is significant risk because wearing the lens continuously overnight while sleeping presents a potential for injuries not normally seen with daily wear lenses, which are non-significant risk.

            A study of a sensor pad to find out if the device can detect the electrical activity of the spinal cord may be non-significant risk, if the study of the sensor pad takes place at the same time as the planned surgical repair of the spinal cord, only if all the following are true:

o       repair of the spinal cord would occur anyway,

o       the sensor pad does not present a potential for serious risk to the health, safety, or welfare of a subject (for example, placing the pad would not prolong or interfere with the operation),

o       the sensor pad is not implanted, and

o       the pad is not of substantial importance in diagnosing, curing, mitigating or treating disease.

The IRB’s NSR determination is important because the IRB serves as the FDA’s surrogate for review, approval, and continuing review of NSR device studies.  The IRB will use the definition of a SR device to determine whether the criteria are met.  In other words, if a device does not meet the definition of a SR device, the IRB may find it to be NSR.

The IRB may agree or disagree with the investigator's or sponsor's initial non-significant risk assessment.  If the IRB agrees the device is NSF and approves the study, the investigation may proceed without FDA approval.  If the IRB disagrees, the investigator or sponsor must notify the FDA that a significant risk determination has been made for the device (whether or not the study is ultimately conducted at UT Southwestern Medical Center or its affiliated institutions).

The FDA may overrule an IRB's decision that a device presents non-significant or significant risk.  When the FDA overrules an IRB's non-significant risk determination, an IDE application must be submitted to FDA.  On the other hand, when the FDA considers the device to be non-significant risk, the FDA may return an IDE application to the investigator or sponsor, and the IRB must then determine whether it wants the study to take place at its institution as a non-significant risk device investigation.

The IRB may be asked to review an SR device study before the sponsor receives FDA approval of an IDE submission.  In this circumstance, the IRB should be aware that, because it is possible that the FDA may not approve the IDE or may request significant changes to the research protocol, the IRB may need to re-evaluate the study after the FDA reviews the application. 

After the determination is made about whether the device is SR or NSR, the criteria for deciding if a study involving the device should be approved are the same as those used to evaluate any proposed research project (i.e., the IRB's determination that risks to subjects are minimized, risks to subjects are reasonable in relation to anticipated benefits and knowledge to be gained, subject selection is equitable, informed consent materials and procedures are adequate, and there are acceptable provisions for monitoring the study and protecting patient information).

The IRB will document its decision in the meeting minutes.  The minutes will describe the IRB’s reason for its SR or NSR determination and may also include the documentation used to establish the IDE status for the study.  For an SR determination, such documentation may include, for example, a copy of the IDE approval or conditional approval letter from the FDA.  For an NSR determination, the documentation may include the FDA's NSR determination (where the agency has made a determination).

When the Investigator is the Sponsor

When the investigator is also the sponsor, the investigator assumes the responsibilities of the sponsor in addition to those of the investigator.  An overview of the general requirements and links to the applicable FDA regulations are listed below.  It is the responsibility of the investigator-sponsor to understand and follow all applicable FDA regulations.

Sponsor Responsibilities for NSR Device Studies:

• Label the device (or its immediate packaging) with the following statement: “CAUTION—Investigational device.  Limited by Federal law to investigational use.”  Other labeling requirements may be applicable.  See the FDA regulations at 21 CFR 812.5,
• Comply with the FDA requirements for monitoring compliance and adverse events at 21 CFR 812.46,
• Maintain accurate and complete records in accordance with FDA regulations at 21 CFR 140 and 21 CFR 150, and report the results to the FDA, IRB and other investigators,
• Ensure that each investigator maintains accurate and complete records and reports the results to appropriate parties in accordance with FDA regulations at 21 CFR 140 and 21 CFR 150, and
• Comply with the FDA regulations at 21 CFR 812.7 prohibiting the promotion or commercialization of the device and/or misrepresentation of the device as safe and effective for the purposes for which it is being investigated.

Sponsor Responsibilities for SR Device Studies:

In addition to the above NSR requirements, sponsors of SR device studies must comply with the following:

• Obtain FDA approval for the investigational device exemption (IDE),
• Select investigator(s) with appropriate training and experience.  ( 21 CFR 812.43),
• Select study monitor in accordance with FDA regulations at 21 CFR 812.43,
• Ship investigational devices only to qualified investigators in accordance with FDA regulations at 21 CFR 812.43,
• Obtain a signed agreement from investigator(s) using the required FDA documents (21 CFR 812.43),
• Supply investigator(s) with copies of the investigational plan and copies of prior device investigations (21 CFR 812.45), and
• Provide required reports to the IRB, investigator(s), and FDA in a timely manner (21 CFR 812.150).