- Adverse Events
- Clinical Investigator
- Early Collaboration
- FDA Contacts
- Foreign Companies/Studies
- Humanitarian Device Exemption
- In Vitro Diagnostic Devices
- Institutional Review Board (IRB)
- New Indication for Marketed Device
- Promotion of Investigational Devices
- Reimbursement Policy
- 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 pre-clinical testing and/or on my clinical protocol?
Yes. There are numerous guidance documents available from FDA that provide recommendations on the pre-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 pre-clinical testing plan and/or a draft clinical protocol. Additional information on Pre-Submissions may be found in the draft guidance “The Pre-Submission Program and Meetings with FDA Staff.” FDA draft guidance represents FDA’s proposed approach to this topic.
Additionally, there are two types of early collaboration meetings available that are discussed in "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 pre-clinical testing or protocols.
I have questions about the IDE regulations. Who should I contact at FDA?
For general questions about the requirements of the IDE regulations, contact:
CDRH-Division of Industry and Consumer Education (DICE)
Center for Devices and Radiological Health
10903 New Hampshire Avenue, WO66-4613
Silver Spring, MD 20993-0002
Phone: 301-796-7100 or 800-638-2041
For specific questions regarding IDE policies or procedures for the review of IDE applications, contact:
CDRH IDE Staff
Investigational Device Exemptions Program
Office of Device Evaluation
Center for Devices and Radiological Health
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
For questions about devices regulated by the Center for Biologic’s Evaluation and Research (CBER), contact CBER’s Office of Communication, Outreach and Development (OCOD):
by writing: (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448
by telephone: 1-800-835-4709 or 301-827-1800
by email: email@example.com
from the Internet at: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm.
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?
Marketing applications may be based on data from studies conducted in other countries. All device studies approved under an Investigational Device Exemption (IDE) are governed by the FDA IDE, Informed Consent, and IRB requirements, even if they include foreign sites in addition to sites in the U.S. [21 CFR 812, 21 CFR 50, 21 CFR 56] Device studies conducted solely at foreign sites are not subject to the IDE requirements.
FDA will accept a foreign clinical study involving a medical device not conducted under an IDE only if the study conforms to whichever of the following provides greater protection of the human subjects:
- the ethical principles contained in the 1983 version of the Declaration of Helsinki, or
- the laws and regulations of the country in which the research was conducted.
When foreign clinical data is used to support a marketing application, the applicant should ensure that the foreign data are applicable to the U.S. population and U.S. medical practice, that the clinical investigators have recognized competence, and that FDA can validate the data through an on-site inspection or other appropriate means, if necessary.
Additional information can be found in the following guidance documents:
My device treats a disease in which only a small number of people are affected. Are there any provisions for these types of devices?
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 can begin.
Additional information on Humanitarian Use Devices.
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 with to act as the IRB for a site. A list of IRBs is available from the CDRH IDE staff at 301-796-5640. (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.
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 my treatment with an investigational device?
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 known 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 CMS.
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 commercial 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.
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 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
- Perspectives on Clinical Studies for Medical Device Submissions (Statistical) - PDF
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 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, 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.