- Adverse Events
- Clinical Investigator
- Early Collaboration
- FDA Contacts
- Foreign Companies/Studies
- In Vitro Diagnostic Devices
- Institutional Review Board (IRB)
- New Indication for Marketed Device
- Promotion of Investigational Devices
- Medicare Coverage
- Significant/Nonsignificant Risk
- Statistical Guidance
- Study Sites
If my device has been approved and marketed in a foreign country and I am conducting clinical trials in the U.S., should I report an adverse event from the U.S. trial under the IDE program or the Medical Device Reporting (MDR) program?
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.
My device is marketed in the U.S. I am conducting a clinical trial in the U.S. for the same device, but for a different indication for use, should I report an adverse event under the IDE program or the MDR program?
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.
Can a clinical investigator submit an IDE?
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.
Does the clinical investigator need to sign form FDA-1572?
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.
Are IDE records released to the public?
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.
Can I receive advice from FDA on non-clinical testing and/or on my clinical protocol?
Yes. There are numerous guidance documents available from FDA that provide recommendations on the non-clinical and clinical testing of specific device types. Additionally, FDA accepts Pre-Submissions, in which you can submit information to FDA and receive advice on topics such as a non-clinical testing plan and/or a draft clinical protocol. Additional information on Pre-Submissions may be found in the FDA guidance "Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program." FDA's guidance represents FDA’s approach to this topic.
Additionally, there are two types of early collaboration meetings available that are discussed in the FDA guidance "Early Collaboration Meetings Under the FDA Modernization Act (FDAMA)". These formal interactions (Determination Meetings and Agreement Meetings) are specific to clinical investigations and do not address non-clinical testing or protocols.
I have questions about the IDE regulations. Who should I contact at CDRH?
For comprehensive regulatory education about medical devices and radiation-emitting products, please see Device Advice and CDRH Learn. Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
For questions about devices regulated by the Center for Biologics Evaluation and Research (CBER), contact CBER’s Office of Communication, Outreach and Development (OCOD) at either 1-800-835-4709 or Industry.Biologics@fda.hhs.gov
Can a foreign company submit an IDE/Is a U.S. Sponsor required?
A foreign company cannot sponsor an IDE; the company 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 regulations.
Do clinical studies have to be conducted in the U.S. / Will foreign studies be accepted?
The FDA continues to promote global harmonization in many aspects of medical device development and regulation, including our commitment to recognize the value of and accept, where appropriate, data from multiple sources and countries.
For more information regarding the FDA’s acceptance of clinical data refer to our page on Acceptance of Data from Clinical Investigations for Medical Devices and the FDA guidance entitled “FDA Acceptance of Clinical Data to Support Medical Device Applications and Submissions Frequently Asked Questions.”.
Do the IDE regulations apply to in vitro diagnostic devices?
Many in vitro diagnostic (IVD) devices are exempt from the IDE regulations. Under section §812.2(c) of the IDE regulations, studies exempt from the IDE regulations include diagnostic devices if 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
- 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 regulations, 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 regulations 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 CDRH IDE Staff at 301-796-5640 or CBER’s OCOD at 301-827-1800 .
Additional guidance for in vitro diagnostic device studies can be found in the guidance “In Vitro Diagnostic (IVD) Device Studies – Frequently Asked Questions.”
Where can I find an IRB?
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 to act as the IRB for a site. Additionally, an IRB reviewing and approving IDE investigations should comply with the requirement of 21 CFR Part 56. Additional information on IRBs is available in the FDA Information Sheets.
Are there special labeling requirements for investigational devices?
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.
Do IDE regulations apply if the device has already been approved for a different indication for use?
Yes, the clinical study of a new indication for an already marketed device falls under the IDE regulations.
Can I advertise my investigational device? What other restrictions apply?
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.
However, the sponsor may advertise for research subjects to solicit their participation in a study. Appropriate advertising methods include but are not necessarily limited to: newspaper, radio, TV, bulletin boards, posters, and flyers that are intended for prospective subjects.
Advertisements should be reviewed and approved by the IRB to assure that they are not unduly coercive and do not promise a certainty of cure beyond what is outlined in the consent and the protocol. No claims should be made, either explicitly or implicitly, that the device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other device.
FDA considers direct advertising for study subjects to be the start of the informed consent and subject selection processes.
Additional guidance is available in the following guidance documents:
Will insurance cover treatment with an investigational device?
For patients with Medicare, the Centers for Medicare and Medicaid Services (CMS) determines whether costs associated with routine care and the investigational devices are covered. To support this determination, the FDA categorizes IDE-approved devices based on whether available data demonstrates that initial questions of safety and effectiveness have been resolved. IDE-approved devices are assigned to one of two categories:
- Category A - Experimental
- Category B - Non Experimental/Investigational
The FDA communicates the assigned category in a formal letter sent to the study sponsor. The sponsor submits the letter to CMS, which considers the FDA-assigned category and other factors to determine whether or not a device meets the requirements for Medicare coverage. The background and criteria associated with the FDA’s categorization process is described in the guidance document titled, “FDA Categorization of IDE Devices to Assist CMS with Coverage Decisions.”
For an IDE-approved device assigned to Category A, CMS may cover only routine care items and services, but not the cost of the device itself. For an IDE-approved device assigned to Category B, CMS may cover routine care items and services as well as the cost of the investigational device if specific criteria are met. If the criteria are not met for a Category B device, neither the device nor other elements of the study are covered by Medicare. To review the criteria and process for requesting coverage for an IDE, the IDE sponsor may refer to their website (Medicare Coverage Related to Investigational Device Exemption (IDE) Studies).
Is my study significant risk or nonsignificant risk?
FDA has a guidance document to help explain how to determine whether a device study is significant or nonsignificant risk. 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.
How many subjects and sites do I have to include in the study?
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 scientifically valid conclusion.
It is recommended that more than one site be included to provide assurance that study results are reproducible.
FDA has developed several guidance documents that address statistics for clinical trials.
- Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests
- Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials
I am a patient. Where can I find a clinical study that will help me?
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 at ClinicalTrials.gov. Please remember that participating in a clinical trial may or may not help you. The safety and effectiveness of an investigational device is not known.
Can the sponsor get a waiver from certain IDE requirements?
Under § 812.10, a sponsor may request FDA to waive any requirement of the IDE regulations. A waiver request with supporting documentation may be submitted as part of an application or separately. FDA may 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.