University of Pennsylvania w Institutional Review Board
Significant Risk/Nonsignificant Risk Determination Form
Investigational Device Exemption Regulations describe 3 types of device studies: exempted from IDE submissions, significant risk, and non-significant risk studies. A subset of research is exempted as described below. For studies that are not exempted, sponsors are responsible for making the initial SR/NSR determination. Unless the FDA has already made the SR/NSR determination, the IRB is required to review the sponsor’s determination.
Is the use of the device in this study exempted from the IDE submission requirements?
Studies exempt from the IDE regulation include:
The device is a legally marketed device and will be used in accordance with its labeling in the proposed research study.
The in vitro diagnostic device complies with the labeling requirements in §809.10(c) and the testing:
Is noninvasive;
Does not require an invasive sampling procedure that presents significant risk;
Does not by design or intention introduce energy into a subject; and
Will not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure;
If YES > STOP. An IDE application is not required. However, IRB approval must be obtained before the study begins.
Is this a significant risk investigation? [21 CFR §812.3(m)]
An IDE is held by the sponsor. If yes, provide appropriate documentation from the sponsor.
An IDE is held by the investigator. If yes, provide appropriate documentation from FDA.
An IDE is being prepared for submission to the IRB. If yes, provide appropriate documentation
when available.
Is this a non-significant risk investigation? [21 CFR §812.3(m)]
Is the device an implant that presents a potential for serious risk to the health, safety, or welfare of a subject? If no, provide protocol specific rationale:
Will the device be used supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject? If no, provide protocol specific rationale:
Will the device be used to diagnose, cure, mitigate, or treat disease or otherwise prevent impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject? If no, provide protocol specific rationale: or,
Does the device otherwise present a potential for serious risk to the health, safety, or welfare of a subject? If no, provide protocol specific rationale:
If NO to all questions (above) > STOP. Submission to and approval from FDA may not required. Submit the study to the IRB for review. The IRB will make the determination regarding the IDE submission requirements. The FDA may be the final arbiter if the sponsor/investigator and the IRB disagree.
If YES to any question (above)> An IDE application must be submitted to the FDA and approval must be obtained from both the FDA and the IRB before study begins.
Note
Use of approved or unapproved devices to evaluate physiology is not FDA-regulated research. For example, use of functional MRI to describe the differences in brain blood flow of normal and schizophrenic individuals is not FDA-regulated research. However, use of functional MRI as a diagnostic tool to differentiate normal and schizophrenic individuals is FDA-regulated research. Whether a study involving a device is FDA-regulated research may come down to whether the purpose of the study is to evaluate participants or to evaluate the device.
The risk determination is based on the proposed use of a device in an investigation, and not on the device alone. Significant risk studies are those that present a potential for serious risk to the health, safety, or welfare of a subject. See the question “What is a Significant Risk Device Study?” for further information. Consider the potential harm the procedure could cause as well as the potential harm caused by the device.
Several examples of determinations from the FDA Guidance follow:
1. 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.
2. 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.
3. An investigational 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, if all the following are true:
- repair of the spinal cord would occur anyway;
- 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);
- the sensor pad is not implanted;
- the pad is not of substantial importance in diagnosing, curing, mitigating or treating disease.
REFERENCES
FDA Information Sheet Guidance for IRB, Clinical Investigator, and Sponsors: Significant and Nonsignificant Risk Medical Device Studies
http://www.fda.gov/oc/ohrt/irbs/devrisk.pdf
FDA Information Sheet Guidance for IRB, Clinical Investigator, and Sponsors: Frequently Asked Questions About Medical Devices
http://www.fda.gov/oc/ohrt/irbs/irbreview.pdf
FDA Center for Devices and Radiologic Health
http://www.fda.gov/cdrh/index.html
FDA Regulations 21 CFR 812
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=812&showFR=1
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