The same basic regulations from the US Code of Federal Regulations (CFR) apply to all clinical investigations of medical devices. These include 21 CFR Part 50 (informed consent), Part 54 (financial disclosure), Part 56 (institutional review boards (IRB)), and Part 812 (investigational device exemptions (IDE)). The IDE regulation:

• stipulates that all studies must be approved by the FDA and IRB before they begin;

• assigns responsibilities to sponsors and investigators; and

• mandates written informed consent for all study subjects.

Device studies conducted to support a US marketing application, or those involving collection of safety and effectiveness information for a new intended (‘offlabel’) use of a marketed device (including studies conducted by ‘sponsor-investigators’ rather than a manufacturer), are all subject to these regulations. Certain clinical studies are exempt from this regulation, including those of devices commercialized prior to 1976 (when the Medical Device Amendments Act was implemented), devices used in studies in accordance with their approved labeling, most studies of in vitro diagnostic devices, consumer preference testing of marketed devices, combinations of legally marketed devices, custom devices, and studies conducted outside the US. Such studies are generally still subject to the informed consent requirement and IRB oversight. If a study is subject to the regulation, then the IRB must determine whether the study is a ‘significant’ or ‘non-significant’ risk. ‘Significant risk’ is defined 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, or 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, or 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.”

If a device is determined significant risk, then the sponsor of the proposed study must submit an IDE application to CDRH. This application is approved, conditionally approved (allowing the study to begin), or disapproved within 30 calendar days. Non-significant risk studies are reviewed and approved by the IRB only, but are still subject to ‘abbreviated’ IDE requirements, including informed consent, monitoring, reporting, labeling, and a prohibition on promotion.

Financial disclosure regulations (21 CFR Part 54) require that the financial involvement of investigators be gathered at the time a ‘covered’ study (one that may ultimately support a marketing application) is conducted and updated annually, but submission of this information to the FDA is only required at the time of a marketing application. Financial compensation is not prohibited, nor is divestiture required.

An IDE application can be sponsored by any US entity, including a manufacturer, contract research organization (CRO), academic investigator, or government agency. The IDE sponsor assumes legal responsibility for compliance with all applicable regulations.

CDRH has developed a highly effective ‘pre-IDE’ program to allow for early informal feedback on preclinical testing and clinical protocols before IDE
applications are submitted. It is also useful for nonsignificant risk or exempt studies, and studies conducted outside the US, intended to eventually support a marketing application but that will not have IDEs associated with them. This program provides a collaborative forum for CDRH and sponsors, enabling earlier consensus on device testing and development, increasing the likelihood of approval of an IDE application, and minimizing surprises. Feedback can be in the form of face-to-face meetings, teleconferences, or electronic mail. Pre-IDE feedback is not legally binding on either the FDA or the sponsor. However, there are also binding ‘determination’ and ‘agreement’ meetings designed to reach formal written consensus on the type of data required for a study, as well as study design parameters, for a particular device (see http://www.fda.gov/cdrh/ode/guidance/310.html).

CDRH has a wealth of information available on regulation of clinical studies of medical devices (see http://www.fda.gov/cdrh).