Introduction
When a patient has a serious or life-threatening condition that is not addressed by current approved treatments, options may exist to use an investigational medical device (i.e., one that has not been approved or cleared by FDA) to treat the patient. Normally, such investigational devices with significant risks may only be used on human subjects through an FDA-approved clinical trial for which an investigational device exemption (IDE) allows the investigational device to be used in a clinical study. However, there are circumstances under which a health care provider may use an investigational device outside of a clinical study to save the life of a patient or to help a patient suffering from a serious disease or condition for which no other alternative therapy exists. The use of an investigational device outside of a clinical trial for treatment of a patient is called “expanded access.” If enrollment in an existing clinical trial protocol is not possible (e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials to address the patient’s condition), patients/physicians have the potential to receive expanded access to investigational devices under one of three alternative mechanisms.
- Emergency Use
- Compassionate Use (or Individual Patient/Small Group Access)
- Treatment Use
FDA approval is required except in the case of emergency use. The mechanisms are summarized below, followed by an in-depth discussion of criteria.
Emergency Use
What is Emergency Use?
Emergency use is the use of an investigational device in an emergency situation. It is intended to provide patients and physicians with access to devices intended to treat life-threatening or serious diseases or conditions when there is no available alternative and no time to obtain FDA approval. Emergency use may apply even if the investigational device is being studied in a clinical trial under an IDE: if a physician needs to use the device in a manner inconsistent with the approved investigational plan; or a physician who is not part of the clinical study, wishes to use the device to treat a patient with a life-threatening or serious disease or condition. Emergency use of an investigational device may occur before an IDE is approved and when a device is not being studied under an IDE.
Criteria:
- The patient has a life-threatening or serious disease or condition that needs immediate treatment;
- No generally acceptable alternative treatment for the condition exists; and
- Because of the immediate need to use the device, there is no time to use existing procedures to obtain FDA approval for the use.
Is FDA approval required prior to Emergency Use?
No. If all of the above criteria are met, an unapproved device may be used in an emergency situation without prior approval by FDA.
FDA expects the physician to make the determination that the patient’s circumstances meet the above criteria, to assess the potential for benefit from the use of the unapproved device, and to have substantial reason to believe that benefits will exist. In the event that a device is used in circumstances meeting the criteria listed above, the physician should follow as many patient protection procedures as possible. Such patient protection procedures include obtaining:
- Informed consent from the patient or a legal representative;
- Clearance from the institution as specified by their policies;
- Concurrence of the IRB chairperson;
- An independent assessment from an uninvolved physician; and
- Authorization from the device manufacturer.
Do I need to report Emergency Use to the FDA?
Yes. If there is an IDE for the device, the IDE sponsor must notify the FDA of the emergency use within 5 days through submission of an IDE Report (§812.35(a)(2)).This follow-up report should include a summary of the conditions constituting the emergency, the patient protection measures that were followed, and patient outcome information.
If no IDE exists, the physician should submit a follow-up report on the use of the device (description of device used, details of the case, and the patient protection measures that were followed) to:
Food and Drug Administration
Center for Devices and Radiological Health
10903 New Hampshire Ave
Document Control Center
WO66 Rm G-609
Silver Spring, MD 20993
[email protected] for assistance.
The physician should not treat the patient identified in the request until FDA approves use of the device under the proposed circumstances. In reviewing this type of request, FDA will consider the above information as well as whether the preliminary evidence of safety and effectiveness justifies such use and whether such use would interfere with the conduct of a clinical trial to support marketing approval.
If the request is approved, the attending physician should devise an appropriate schedule for monitoring the patient, taking into consideration the investigational nature of the device and the specific needs of the patient. The patient should be monitored to detect any possible problems arising from the use of the device.
The above compassionate use criteria and procedures can also be applied when a physician wishes to treat a few patients rather than an individual patient suffering from a serious disease or condition for which no alternative therapy adequately meets their medical need. In this case, that the request should include the information identified above and indicate the number of patients to be treated. If there is an IDE for the device, the supplement should include the protocol to be followed or should identify deviations from the approved clinical protocol. As with single patient compassionate use, a monitoring schedule should be designed to meet the needs of the patients while recognizing the investigational nature of the device. Follow-up information on the use of the device should be submitted in a report after all compassionate use patients have been treated.
What actions does FDA take on Compassionate Use requests?
After a compassionate use request is received, FDA will approve, approve with conditions, or disapprove the request. When there is an IDE for the device, compassionate use request IDE supplements have the same statutory 30-day review cycle as other IDE submissions. However, the patient need is considered when reviewing these requests and they are often expedited if necessary. For example, in 2015, compassionate use requests received under an IDE were reviewed in as little as 1 day, and on average in 18 days. Compassionate use requests received without an IDE were reviewed in as little as the same day as receipt, and on average in 10 days.
Do I need to report anything to FDA after the Compassionate Use occurs?
Yes. Following the compassionate use of the device, a follow-up report should be submitted by whoever submitted the original compassionate use request to FDA. This report should present summary information regarding patient outcome. If any problems occurred as a result of device use, these should be discussed in the follow-up report and reported to the reviewing IRB as soon as possible.
How many Compassionate Use requests does FDA/CDRH receive each year?
COMPASSIONATE USE IDE SUPPLEMENTS
*Excludes those withdrawn or converted to Emergency Use while under review
**Based on Evaluable Submissions
COMPASSIONATE USE REQUESTS WITHOUT AN IDE
*Excludes those withdrawn or converted to Emergency Use while under review
**Based on Evaluable Submissions
Approval Process, FDA Actions, for additional information;
- may be effective for its intended use in its intended population; or
- would not expose the patients to whom the device is to be administered to an unreasonable and significant additional risk of illness or injury;
Safeguards
Treatment use of an investigational device is conditioned upon the sponsor and investigators complying with the safeguards of the IDE process and the regulations governing informed consent (21 CFR 50) and institutional review boards (21 CFR 56).
What are the reporting requirements for a Treatment Use IDE?
The sponsor of a treatment IDE must submit progress reports on a semi-annual basis to all reviewing IRB’s and FDA until the filing of a marketing application. The dates of these reports are based on the period of time since initial approval of the treatment IDE. After filing of a marketing application, progress reports must be submitted annually in accordance with the IDE regulations.
See “Suggested Format For IDE Progress Report” under Reports for guidance on the content of a progress report. The progress report must also include the number of patients treated with the device under the treatment IDE, the names of the investigators participating in the treatment IDE, and a brief description of the sponsor’s efforts to pursue marketing approval / clearance of the device.
The sponsor of a treatment IDE is responsible for submitting all other reports required under §812.150 (Reports), such as unanticipated adverse device effects and final reports. The reports are submitted as reports to the original IDE application. See Reports for additional guidance.