The majority of IDE studies are conducted to collect safety and effectiveness data used to support Premarket Approval (PMA) applications submitted to the FDA.

Examples: Significant risk studies involve implantable devices such as cardiac pacemakers, orthopedic implants and stents. Significant risk studies can also involve products not introduced into the body, such as computer software used for prenatal risk evaluation. Each of these studies would require an IDE.

Note: See UCSF guidance on Significant and Non-Significant Risk Devices for more information.

This includes both a device being used or tested in a new way that significantly increases the risks associated with the device and/or significant risk studies testing an FDA-approved device.

Examples: A legally marketed coronary stent would be considered an investigational device and would require an IDE if used as part of a study to collect safety and effectiveness data for treating conditions involving other vascular sites.

• IRB review and approval is required for all non-significant risk device studies.
• The FDA authorizes institutional review boards to conduct a risk assessment of all proposed non-significant risk studies. However, IRB cannot override NSR FDA determination if one has previously been made.
• Study approval is dependent on the investigator supplying the IRB with sufficient information, generally provided by the study sponsor, regarding the device and its intended use.
• If the IRB determines that a proposed non-significant risk study is actually a significant risk study, the sponsor must submit a report to the FDA as explained here.

For more information, see UCSF guidance on Significant and Non-Significant Risk Devices.

Examples: Non-significant risk devices include daily wear contact lenses and associated care products; conventional gastroenterology and urology endoscopes; externally worn monitors for insulin reactions; and non-implantable electrical incontinence devices.

A physician can use a legally marketed device without IRB approval for any condition or disease within a “legitimate healthcare practitioner-patient relationship.” However, the results of an off-label use of a medical device cannot be presented as research.

• IRB Application: 
  • Indicate that the study involves a device in the "Initial Screening Questions" section. 
  • Check the appropriate box in the "Drugs and Devices" section of the IRB Application.
• An IDE number: If the sponsor’s protocol does not list the IDE number, you must submit documentation from the sponsor or FDA identifying the IDE number for this study. The IRB will not issue final approval until the IDE number is reported to and verified by the IRB. However, the IRB will review the research before the IDE application is submitted to the FDA.
• Investigator’s Brochure
• Directions for use, typically provided by the manufacturer and device labeling consistent with federal regulations [21 CFR 812.5]
• Scientific/sponsor's protocol: This document should describe the methodology to be used and offer an analysis that the study is scientifically sound.
• An explanation of the device cost, which is determined by the reimbursement category provided by FDA with each approved IDE. This information is needed for the consent form.
• Clearance from the Radiation Safety Committee for radiation-emitting devices.

• IRB Application: 
  • Indicate that the study involves a device in the "Initial Screening Questions" section. 
  • Check the appropriate box in the "Drugs and Devices" section of the IRB Application
  • Check Yes when asked if a Non-Significant Risk (NSR) determination is being requested for the investigational device. Then complete the "Non-Significant Risk Determination for an Investigational Device" section to provide the IRB with adequate justification why the use of the device in this study poses non-significant risk.
• Detailed device information from the sponsor, such as a description of the device and how it is used.
• Diagrams and/or in situ photographs of the device are very useful (attach as "Other Study Documents").
• Directions for use, typically provided by the sponsor or manufacturer and device labeling consistent with federal regulations [21 CFR 812.5].
• Scientific/sponsor's protocol: This document should describe the methodology to be used and offer an analysis that the study is scientifically sound.
• An explanation of the device cost: Non-significant risk devices are placed in Category B and are most likely eligible for reimbursement. See the reimbursement category overview provided by the FDA.

• Must include a clear statement that the device is investigational and has not been approved by the FDA for clinical use or, if applicable, that the device has been approved for specific clinical indications but not for the use being studied.
• Should include a brief lay description of the device and what it is designed to do.
• Must not describe the issuance of an IDE as an approval or endorsement by the FDA.

Must state that the FDA may review research and subjects’ medical records to verify study data.

• All investigators have an obligation to report certain adverse events directly to the IRB.
• Under IDE regulations, there are additional and separate federal requirements for reporting adverse events to the FDA. When the study sponsor holds the IDE, investigators need to report all adverse events to the sponsor and the sponsor will submit appropriate reports to the FDA.

An IDE application submitted by a sponsor seeking FDA clearance to market a medical device.

By submitting an IDE application to the FDA and conducting the clinical investigation, a physician takes on the responsibilities of both “sponsor” and “investigator.”

This is an exception to investigational device regulations permitting the one-time treatment of one patient per institution without prior FDA approval.

• Every effort must be made to obtain prior authorization from the IRB; at minimum at UCSF an IRB Chair must concur before treatment begins.
• Strict reporting requirements apply.
• The emergency use of an investigational device must meet all of the following criteria:
  • the patient has a life-threatening or severely debilitating condition, and
  • there are no other available treatments, and
  • there is not sufficient time for prior IRB review and approval.

Note: Research may not be conducted under an emergency use IDE. Subsequent use(s) of the emergency use investigational device require prior IRB review and approval. For more information, please review the UCSF guidelines for Emergency Use of Experimental Drugs and Devices.

See discussion in section above.

Under an existing IDE, the FDA may allow treatment for an individual or a small number of seriously ill patients who have (a) a life-threatening disease or condition(b) with no other generally acceptable alternative treatment for the condition and (c) there is an existing concurrent clinical trial but the patient(s) do not meet the inclusion criteria and (d) the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease. The FDA requires the sponsor/investigator either to supply a supplement to an existing IDE justifying the compassionate use or to request a new IDE.

Note: Compassionate use requires FDA review and IRB approval before treatment can be initiated. The study involving the existing IDE must already be approved by the IRB. See the Emergency Use and Compassionate Use of Experimental Drugs and Devices page for more info.

If during the course of a clinical trial the data suggests that the device is effective, then the trial may be expanded to include additional patients with life-threatening or serious diseases for whom no comparable or satisfactory alternative is available. In addition, the sponsor of the controlled trial must be pursing marketing approval/clearance of the device. Note: Treatment use may begin 30 days after the FDA has received the treatment IDE submission, or earlier if FDA notifies the sponsor in writing. Prior IRB review and approval are also required.

Continued Access (Example of Treatment Use)A common type of treatment use occurs when after the completion of a controlled clinical trial, a supplement to an existing IDE is submitted and the FDA allows continued access to the device provided there are no safety concerns. The Continued Access Policy creates a bridge and allows access to promising devices while the marketing application is being prepared by the sponsor or reviewed by the FDA.

Investigators conducting studies in which an investigational device will be used must ensure adequate control of the device. Adequate control and handling of investigational devices include all of the following:

• The investigator must ensure that the investigational device is used only in accordance with the IRB-approved protocol, the signed agreement, the investigational plan and applicable FDA regulations.
• The investigator must administer the investigational device only to participants under the investigator’s direct personal supervision or under the supervision of a sub-investigator directly responsible to the investigator.
• The investigator must not supply the investigational device to any person not authorized to receive it.
• The investigation must maintain the following accurate, complete, and current records relating to the investigator’s participation in an investigation.
  • Records of receipt, use or disposition of a device that relate to a) The type and quantity of the device, the dates of its receipt, and the batch number or code mark; b) the names of all persons who received, used, or disposed of each device; c) why and how many units of the device have been returned to the sponsor, repaired, or otherwise disposed of.
• If the investigation is terminated, suspended, discontinued, or completed, the investigator must return any unused supplies of the investigational device to the study sponsor, or otherwise provide for disposition of the unused supplies as directed by the sponsor.

Here is a sample Investigational Device Accountability Log you can use.

A complete overview of medical device import/export regulations is provided by the CDRH. Clinical investigators should be aware that FDA does not recognize regulatory approvals from other countries; therefore, an imported medical device must meet all FDA requirements. The IDE sponsor must be located in the United States. Anyone who intends to import an investigational device takes on the responsibilities of a sponsor.