August 26, 2014
In its August 19 guidance for Investigation Device Exemption (IDE) Clinical Investigators, the FDA attempts to better outline its thought process for reviewing, accepting, accepting with conditions or denying an IDE. It can literally be a matter of life and death for patients and trial subjects. Thus, the agency and industry continue to take it seriously.
FDA approval of an IDE allows the initiation of subject enrollment in a clinical investigation of a medical device that has potentially significant risks — widely defined as a device that could pose a serious health risk or death to the user, is used to support to prolong life, or is part of a diagnosis tool also being used to support or sustain life.
The guidance covers a number of important areas, some with new wrinkles, including:
IDE Decisions
The FDA must inform sponsors or sponsor-investigators of its decision, or notify the sponsor that the investigation may not begin, within 30 days from the date of receipt of the IDE application; otherwise, the IDE application will be deemed approved. If an IDE application is approved or approved with conditions, the sponsor may begin subject enrollment, up to the number of subjects and investigational sites specified in the FDA’s decision letter, upon receipt of Institutional Review Board (IRB) approval, which may occur prior to FDA approval.
IDE Approval
An IDE application is approved if the FDA has determined that: the sponsor has provided sufficient data to support initiation of a human clinical study; no subject protection concerns preclude initiation of the investigation, and no additional conditions must be met.
IDE Approval with Conditions
The FDA has clarified matters somewhat and appears to have given the industry a bit more leeway, provided it is used wisely and safely.
If FDA approves an IDE application with conditions, the sponsor may begin subject enrollment upon receipt of IRB approval and in accordance with the limits described in FDA’s decision letter, including the maximum numbers of U.S. subjects and investigational sites, and must submit information addressing the issues identified as conditions of approval in FDA’s letter within 45 days.
An IDE application is approved with conditions if the FDA has determined that: the sponsor has provided sufficient data to support initiation of subject enrollment in a human clinical study; no subject protection concerns preclude initiation of subject enrollment, but additional conditions must be met to address certain outstanding issues.
Previously known as “conditional approval,” the phrase “approval with conditions” is now used to convey that the outstanding issues do not raise concerns that preclude the FDA from granting approval for initiation of subject enrollment in the clinical investigation. The FDA now states that the resolution of these issues isn’t required prior to the initiation of subject enrollment in the study, except for certain issues related to the informed consent document.
The guidance reiterates how seriously the FDA takes clear, simply informed consent forms for trial participants, noting it “closely reviews” those as part of an IDE determination.
Staged Approval, Staged Approval with Conditions
In the guidance, the FDA states that it may grant IDE approval or approval with conditions for a portion of the intended study cohort, allowing certain outstanding questions to be addressed concurrently with enrollment in this cohort. Staged approval allows the clinical investigation to commence in a timely manner while ensuring adequate subject protections. In some cases, the sponsor proposes a staged enrollment in the IDE application. In other cases, the sponsor requests approval for the full subject cohort, but the agency may decide to grant staged approval for a limited number of subjects as an alternative to outright disapproving the IDE.
IDE Disapproval
Broadly speaking, little has changed regarding what the FDA deems most important in an IDE request. If the agency raises patient risk issues that the device company cannot adequately address, and/or if the device maker is unable to persuade the FDA that the product is sufficiently important (e.g., life-saving) to qualify for IDE designation, it will receive a thumbs down.
FDA Communications
The agency states that it will send a letter addressing any rejection or questions regarding an IDE request. The letter should include the agency’s thoughts on how the study design assessment, considerations, and other suggested improvements the device maker should consider if it plans to try again.
Author: Michael Causey, Editor & Publisher, eDataIntegrityReport.com
