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THE COMMITTEE ON HUMAN RESEARCH
UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES
SIGNIFICANT AND NON-SIGNIFICANT
RISK DEVICES
(August 2005, Revised February 2008)
Brief Overview
Definition of Significant Risk
The IRB Decision-Making Process
CHR Application Requirements
Decision to Approve or Disapprove
Non-Significant/Significant Risk Decision
Examples of Non-Significant and Significant
Risk Devices
Note: If your investigation involves a medical device, please also read HRPP Guidance on Investigational Devices.
Brief Overview
FDA regulations (21 CFR 812.2) 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 determination of "non-significant risk" from the institutional review board. FDA “Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, Medical Devices” provides criteria for the investigator and institutional review board to use in making these decisions.
The CHR Supplement, Non-Significant Risk Determination for an Investigational Device, must be attached to any CHR application involving non-significant risk devices.
Definition of a Significant Risk Device
21 CFR 812.3 definies a Significant Risk Device as 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 a use in 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.
A non-significant risk (NSR) device is one that does not meet the definition of a significant risk device.
The IRB Decision-Making Process
An institutional
review board must make two separate decisions, based on different criteria.
First: Is the investigation approvable or not? Second: Does the device present
significant or non-significant risk? (If NSR, an IDE can
be given by the board. If not, the investigator must be advised to seek
a SR IDE from the FDA).
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CHR Application Requirements
If the investigator or sponsor believes a device poses non-significant risk, the CHR Application should include a completed CHR Supplement, Non-Significant Risk Determination
For An Investigational Device. Additional supporting information (e.g., any reports of prior investigations) should be submitted as appropriate. The CHR should also be informed if the FDA or any other IRB has determined the device to present significant or non-significant risk, and provide any further information requested by the CHR.
Decision to Approve or Disapprove
The criteria
for deciding if a study involving either a significant or non-significant
risk 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.
Non-Significant/Significant Risk Decision
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A. |
The
CHR may agree or disagree with the investigator's or sponsor's
initial non-significant risk assessment. If the CHR agrees, and
approves the study, the investigation may proceed without FDA
approval. If the CHR disagrees, the study can only be conducted
at this institution as a study involving a significant risk device,
and 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 that institution).
While
the institutional review board is serving as FDA's surrogate with
respect to review and approval of non-significant risk devices,
the ultimate decision in determining if a device is SR or
NSR is the FDA's. On some occasions, FDA may overrule
an IRB's decision that a device presents non-significant
or significant risk. When FDA overrules an IRB's non-significant
risk determination, an IDE application must be submitted to FDA.
On the other hand, when FDA considers the device to be non-significant
risk, FDA may return an IDE application to the investigator or
sponsor, and the IRB must then determine if it wants the study
to take place at its institution as a non-significant risk device
investigation. |
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B. |
Criteria for Determining Significant vs. Non-Significant Risk
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 the device, the IRB must consider the potential
harm caused by the procedure 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. Some examples follow: |
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A pacemaker that is a modification of a commercially
available pacemaker poses a significant risk because the use of any
pacemaker
presents a potential for serious harm to the subjects. This is true
even though the modified pacemaker may pose less risk, or only slightly
greater risk, in comparison to the commercially available model.
The degree of possibly reduced or increased risk associated with
the investigational pacemaker should only be considered (in relation
to possible decreased or increased benefits) when assessing the
approvability of the study.
An extended-wear contact lens is considered significant
risk because wearing the lens continuously for 30 days presents
a potential for injuries not normally seen with daily wear lenses,
which are considered non-significant risk. |
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Examples of Non-Significant
Risk and Significant Risk Devices
Please refer to FDA “Guidance for Institutional Review Boards and Clinical Investigators, 1998 Update, Medical Devices” for examples of non-significant and significant risk devices.
To find information on a specific device or type of device, search
the
database maintained by CDRH.
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