Frequently Asked Questions

• Adverse Events
• Clinical Investigator
• Confidentiality
• Early Collaboration
• FDA Contacts
• Foreign Companies/Studies
• Humanitarian Device Exemption
• In Vitro Diagnostic Devices
• Institutional Review Board (IRB)
• Labeling
• New Indication for Marketed Device
• Promotion of Investigational Devices
• Reimbursement Policy
• Significant/Nonsignificant Risk
• Statistical Guidance
• Study Sites
• Waivers

If your device is not marketed in the U.S., you should report an adverse event under the IDE program (812.150). The sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs and investigators within 10 working days after the sponsor first receives notice of the adverse effect.

If the adverse event occurs in a foreign country in which it is legally marketed and not under the control of a clinical study, the adverse event should be discussed in the IDE progress report since the adverse information may affect risk analysis.

The adverse event should not be reported under the MDR program because the MDR program only applies to medical devices that are legally marketed in the U.S.

Adverse events that occur in subjects enrolled in the clinical trial should be reported under the IDE program (812.150). The sponsor must report the results of an evaluation of an unanticipated adverse device effect to FDA and all reviewing IRBs and investigators within 10 working days after the sponsor first receives notice of the adverse effect.

Adverse events that occur in the U.S. but outside of the clinical trial would be reported through MDR; however, the adverse event should be discussed in the IDE progress report since the adverse information may affect risk analysis.

Yes, a clinical investigator can sponsor his/her own study in which case they are considered a sponsor-investigator and must comply with all the responsibilities of both the sponsor and investigator.

No, this is a form used for drug studies. For device studies, the sponsor should develop an investigators agreement which includes the elements of 21 CFR 812.43(c). The sponsor should have all investigators sign the agreement prior to participating in the study.

FDA will not disclose the existence of an IDE unless:

• FDA determines that the information had been previously disclosed to the public;
• FDA approves a PMA for a device subject to an IDE; or
• a notice of completion of a Product Development Protocol (PDP) is in effect.

If the existence of an IDE file has not been publicly disclosed or acknowledged, no data or information in the file are available for public disclosure except for information on banned devices and a report of an adverse effect to an individual on whom an investigational device has been used. [(§812.38)]

Data or information contained in the file is not available for public disclosure before approval of an application for PMA or the effective date of a notice of completion of a PDP. Upon approval FDA will release a summary of the safety and effectiveness data on which the decision was based. Other disclosable information available after the device has been approved includes any protocol for a test or study, adverse reaction reports, and correspondence after confidential information has been deleted. Information available for public disclosure is outlined in 21 CFR 814 Premarket Approval of Medical Devices section §814.9.

Yes. There are numerous guidance documents available from FDA that provide recommendations on the pre-clinical and clinical testing of devices. Additionally, FDA accepts pre-IDE submissions where you can submit information to FDA and receive advice. This may include a pre-clinical testing plan and/or a draft clinical protocol. Additional information on pre-IDE submissions may be found in the documents "Goals and Initiatives for the IDE Program" http://www.fda.gov/cdrh/d951.html and "Pre-IDE Program: Issues and Answers" http://www.fda.gov/cdrh/ode/d99-1.html.

Additionally, there are two types of early collaboration meetings available that are discussed in "Early Collaboration Meetings Under the FDA Modernization Act (FDAMA)
http://www.fda.gov/cdrh/ode/guidance/310.html
http://www.fda.gov/cdrh/ode/guidance/310.pdf

For general questions about the requirements of the IDE regulation, contact:

For specific questions regarding IDE policies or procedures for the review of IDE applications, contact:

IDE Staff
Investigational Device Exemptions Program (HFZ-403)
Office of Device Evaluation
Center for Devices and Radiological Health
9200 Corporate Boulevard
Rockville, MD 20850-3223
Telephone 240-276-4040

A foreign company cannot sponsor an IDE; they must have a U.S. agent who acts as the sponsor (see 21 CFR 812.18(a)). The U.S. agent must fulfill all the responsibilities of a sponsor identified in the IDE regulation.

Marketing applications may be based on data from studies conducted in other countries. All device studies conducted outside of the U.S. but approved under an Investigational Device Exemption (IDE) are governed by the FDAs IDE, Informed Consent, and IRB requirements. [21 CFR 812, 21 CFR 50, 21 CFR 56]

Yes. The Safe Medical Devices Act (SMDA) of 1990 provided for a humanitarian device exemption to encourage the discovery and use of devices that benefit fewer than 4,000 individuals in the U.S. This provision allows FDA to grant an exemption from the effectiveness requirements of sections 514 (Special Controls) and 515 (Premarket Approval) of the FD&C Act after finding that:

• the device is designed to treat or diagnose a disease or condition that affects fewer than 4,000 individuals per year in the U.S.;
• the device is not available otherwise, and there is no comparable device available to treat or diagnose the disease or condition; and
• the device will not expose patients to unreasonable or significant risk, and the benefits to health from the use outweigh the risks.

Devices granted an exemption may only be used at facilities that have an established institutional review committee, and the humanitarian use must be approved by the committee before use begin. 

Additional information on Humanitarian Use Devices can be found at http://www.fda.gov/cdrh/ode/hdeinfo.html. 

Many in vitro diagnostic (IVD) devices are exempt from the IDE regulations. Under section §812.2(c) of the IDE regulation, studies exempt from the IDE regulation include diagnostic devices if the testing:

1. is noninvasive;
2. does not require an invasive sampling procedure that presents significant risk;
3. does not by design or intention introduce energy into a subject; and
4. is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure;

IVD devices that are under study, including IVD devices that are exempt from the IDE regulation, must comply with labeling requirements under 21 CFR 809.10(c)(2).    One of two statements is required, as applicable for each case: "For Research Use Only. Not for use in diagnostic procedures", or "For Investigational Use Only. The performance characteristics of this product have not been established."

Studies which are exempt from the requirements of the IDE regulation are not exempt from the requirements for IRB review and approval under Part 56 and the requirements for obtaining informed consent under Part 50. In addition, IDE exempt studies are not exempt from §812.119, Disqualification of a clinical investigator. 

For guidance regarding the applicability of these regulations with respect to investigations being conducted under the provisions of §812.2(c), contact the reviewing IRB and/or the IDE Staff at 240-276-4040.

Additional guidance for in vitro diagnostic device studies can be found in "Regulating In Vitro Diagnostic Device (IVD) Studies." http://www.fda.gov/cdrh/comp/ivdreg.html

The institutions where the study is to be conducted should be contacted to determine if they have their own IRB. If the study is conducted at a site that does not have its own IRB, the investigators should be queried to see if they are affiliated with an institution with an IRB that would be willing to act as the IRB for that site in the study. There are also independent/contract IRBs that can be contracted with to act as the IRB for a site. A list of IRBs is available from the IDE staff at 30240-276-4040. (Please note: FDA does not approve or endorse any IRBs.) Additionally, an IRB can be established in accordance with 21 CFR 56. Additional information on IRBs is available in the FDA Information Sheets located at http://www.fda.gov/oc/ohrt/irbs/default.htm

Yes. Under § 812.5 an investigational device or its immediate package must bear a label with the following information:

• the name and place of business of the manufacturer, packer, or distributor;
• the quantity of contents, if appropriate; and
• the statement, "CAUTION ­­ Investigational device. Limited by Federal (or United States) law to investigational use."

The label must also describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.

The labeling of an investigational device must not contain any false or misleading statements nor imply that the device is safe or effective for the purposes being investigated.

If the investigational device is used solely for research on laboratory animals, the label must contain the following statement: "CAUTION ­­ Device for investigational use in laboratory animals or other tests that do not involve human subjects."

The sponsor should provide detailed information on device labeling in the investigational plan. This information may vary depending on the device and the nature of the study. Product labeling should be sufficient to ensure stability of the test article for the duration of the study (storage requirements, calibration procedures), bear sufficient directions for proper administration, and detail procedures to follow in the event of patient injury.

Yes, the clinical study of a new indication for an already marketed device falls under the IDE regulation.

Under § 812.7, a sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator cannot:

• Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.
• Commercialize an investigational device by charging the subjects or investigators a higher price than that necessary to recover costs of manufacture, research, development, and handling.
• Unduly prolong an investigation. If data developed by the investigation indicate that premarket approval (PMA) cannot be justified, the sponsor must promptly terminate the investigation.
• Represent that an investigational device is safe or effective.

In the past Medicare coverage was denied for devices which were under an IDE and had not yet received premarket notification clearance and/or premarket approval because the treatments were considered experimental. However, there are devices which are refinements of existing technologies or replications of existing technologies made by other manufacturers. Many of these devices are under an FDA-approved IDE as a means of gathering the scientific information needed for FDA to establish the safety and effectiveness of that particular device, even though there is evidence that the device type can be safe and effective.

On September 8, 1995, FDA entered into an agreement with the administrator of the Medicare program, the Health Care Finance Administration (HCFA), to provide information about devices under an IDE to aid in its reimbursement decisions. [Please note that HCFA is now know as the Centers for Medicare & Medicaid Services (CMS).] Under this agreement certain devices could be viewed as "reasonable and necessary" by Medicare and treatments could be covered if all other applicable Medicare coverage requirements are met. Specifically, FDA will place all IDEs it approves in one of two categories:

Category A - Experimental

The IDE involves innovative devices in which "absolute risk" has not been established (i.e., initial questions of safety and effectiveness have not been resolved and thus FDA is unsure whether the device type can be safe and effective)

Category B - Investigational; Non-experimental

The clinical investigations involves device types believed to be in classes I or II or device types believed to be in class III where the incremental risk is the primary risk in question (i.e., underlying questions of safety and effectiveness of that device type have been resolved). This category includes device types that can be safe and effective because, for example, other manufacturers have obtained FDA approval for that device type. Nonsignificant risk studies may also be included in this category.

FDA provides the category determination on the IDE approval letter to the sponsor and also forwards this information to HCFA.

It is hoped that this agreement will provide Medicare beneficiaries with greater access to advances in medical technology and encourage clinical researchers to conduct high quality studies of newer technologies.

Please note that this agreement covers Medicare coverage only. FDA has no authority over commerical health insurance carriers. Many commercial health insurance carriers do not cover any investigational devices. It is advised that you check with your insurance company before you receive treatment with an investigational device.

For additional guidance, see "Implementation of the FDA/HCFA Interagency Agreement Regarding Reimbursement Categorization of Investigational Devices 9/15/95 (D95-2)" http://www.fda.gov/cdrh/d952.html

FDA has a guidance document to help explain how to determine whether a device study is significant or nonsignificant risk. It is located at http://www.fda.gov/oc/ohrt/irbs/devrisk.pdf. If the sponsor believes a device study is nonsignificant risk, the sponsor can provide information to the IRBs reviewing the study explaining why the device study does not pose a significant risk. If the IRBs agree and approve the study, the research may be conducted and FDA does not need to be notified. However, if an IRB determines the study is significant risk, the sponsor must notify FDA in writing (21 CFR 812.150(b)(9)). The study may not begin until FDA approves the study or provides a determination that the investigation is nonsignificant risk.

The number of subjects and sites to include in a study depends on the study objectives and the study design needed to result in a statistically valid conclusion.

It is recommended that more than one site be included in order to provide assurance that study results are reproducible.

FDA has developed guidance documents to assist manufacturers in developing a statistically valid study.

• Statistical Guidance for Clinical Trials of Non Diagnostic Medical Devices http://www.fda.gov/cdrh/ode/ot476.html
• Perspectives on Clinical Studies for Medical Device Submissions (Statistical)-PDF http://www.fda.gov/cdrh/ode/78.pdf

There is no centralized repository for information on device clinical trials. Your health care provider may be able to provide information. Hospitals associated with medical schools are often involved in research and institutions that are participating in clinical trials will sometimes place advertisements in newspapers or magazines to recruit subjects.

At this time, FDA does not maintain a clinical trials database for medical devices and our regulations do not permit us to release information regarding investigational devices. However, the National Institutes of Health maintains a clinical trials database for trials that they support. It may be accessed through the Internet: http://clinicaltrials.gov

Please remember that participating in a clinical trial may not help you. The safety and effectiveness of an investigational device is not known.

Under § 812.10, a sponsor may request FDA to waive any requirement of the IDE regulation. A waiver request with supporting documentation may be submitted as part of an application or separately. FDA may, by letter, grant a waiver of any requirement that is not required by the FD&C Act and that is unnecessary to protect the human subject by providing a letter to the sponsor outlining the waiver.

Example of an FDA letter granting a waiver for additional investigational sites: http://www.fda.gov/cdrh/manual/waiver.html