What you need to know about compassionate and emergency uses of investigational and unapproved devices.
The views and opinions in this article are those of the author and do not necessarily reflect those of the US FDA, the US Department of Health and Human Services, or the Public Health Service.
The FDA acknowledges that when a patient presents with a serious or life-threatening condition and there is not a generally acceptable alternative treatment, the best treatment option for the patient may be the use of an investigational device. As such, provisions have been developed to allow patients to be treated with an investigational device under special circumstances that are beyond the scope of a clinical study (visit http://www.fda.gov/cdrh/ode/idepolcy.pdf). This column addresses some of the commonly asked questions regarding the emergency use and compassionate use ?expanded access? provisions of the Investigational Device Exemptions (IDE) regulations as well as the emergency use of an unapproved device.
Q: What are the definitions of compassionate use and emergency use?
A: If a patient has a serious disease or condition that needs immediate treatment, does not meet the entrance criteria for the clinical study and does not have a generally acceptable alternative treatment option, they may receive an investigational medical device and be treated as an emergency use. Prior FDA approval is not required; however, the FDA needs to be notified of each emergency-use case. Within 5 working days of being notified of an emergency-use case, the sponsor of an IDE application must submit an IDE supplement to the FDA. The report should include a summary of the emergency-use conditions, the patient protection measures that were followed, and patient outcome information. Patient protection measures include: (1) obtaining informed consent from the patient or legally authorized representative; (2) obtaining clearance from the institution in accordance with their policies; (3) concurrence from the institutional review board (IRB) chairperson; (4) getting an independent assessment from an uninvolved physician; and (5) getting authorization from the IDE sponsor. The IDE supplement should clearly state which of these patient protection measures were followed.
For patients who do not meet the entrance criteria for the clinical study, who are faced with a serious disease or condition and who have no comparable or satisfactory alternative therapy available, the FDA allows individual patient access or compassionate use of an investigational device. In these cases, the sponsor must obtain prior FDA approval on a patient-by-patient basis. In order to obtain FDA approval, the sponsor of the IDE submits an IDE supplement requesting approval for a protocol deviation. The supplement should include a description of the patient’s condition and the circumstances that require treatment with the investigational device; a discussion of why other options are unavailable or unsatisfactory; and a discussion of why the probable risk of using the investigational device is no greater than the probable risk of the disease or condition. In addition, the supplement should outline any deviations to the approved clinical protocol that are required to treat the patient and the patient protection measures taken, comparable to those listed for emergency use.
If treatment of the patient would include the use of an unapproved medical device, that is, a device not being investigated under an IDE, the emergency use provisions listed in the “Guidance for the Emergency Use of Unapproved Medical Devices; Availability” should be followed. This guidance was published in a Federal Register Notice dated October 22, 1985. In this case, the procedures to be followed are comparable to those for an emergency use under the auspices of an IDE, except that the report is sent to the IDE staff at the FDA. The guidance specifically mentions that an approved IDE would be needed for subsequent uses of the device, that is, this mechanism should not be used as an alternative method for allowing multiple uses of an unapproved medical device.
Q: What is the difference between compassionate use and emergency use?
A: The difference has been described to me by one physician as follows: all of them are compassionate uses, it’s just that some are emergent and others are not. This is correct as far as the logic; that is, these patients do not meet the selection criteria for the study so could be considered to be ?compassionate uses,? as the term is generally applied. However, the FDA tends to have specific definitions of words that are included in regulations and guidances. For medical devices, compassionate use is the term applied when there is time to obtain prior FDA approval and an emergency use is the term applied when there is a need to provide immediate treatment. As an example, in an endovascular graft study for treatment of AAAs, both emergency use and compassionate use patients may have comorbidities (ie, of high risk of morbidity and mortality with standard surgical repair) or lesion types (eg, pseudoaneurysms, dissections) that would preclude them from being enrolled in the IDE study. The difference between these patients relates to the urgency of the situation. If there is not time to request and receive prior FDA approval, the treatment would fall under emergency use. If there is adequate time, the treatment would fall under compassionate use.
Q: Is the current definition of emergency use sufficient to allow unique life-saving technology to be used when necessary?
A: The emergency use provisions are not intended to provide a mechanism for widespread use of a technology. The intent is to allow for limited access in specific situations until appropriate alternative regulatory options can be used. For example, studies of endovascular grafts can include arms of the study for patients with different types of lesions or who are of high risk of morbidity and mortality with surgical repair. This pathway results in the collection of data that may ultimately be useful for clinicians once the device is marketed. Even if such additional arms are incorporated, there may still be a need for emergency uses in unique situations.
Care must be taken in defining “necessary.” The medical device regulations require that such devices be demonstrated to be reasonably safe and effective before being approved. The emphasis should be placed on the collection of the appropriate data needed to verify that the device is truly a viable treatment option for these patients.
Q: Do physicians need prior approval? If so, how long does it take?
A: As noted above, emergency uses do not require prior FDA approval. The amount of time needed to follow the appropriate patient protection procedures and obtain the device from the manufacturer dictates the timing of the treatment. Compassionate uses require prior FDA approval. The FDA strives to provide verbal feedback or approval within 5 days of receipt of a compassionate use request, with a written response mandated within 30 days.
Q: What are the roles of individual institutions and IRBs in the emergency use process?
A: Prior IRB approval is not required for emergency use. If possible, concurrence of the IRB chairperson should be obtained, but it is not required. A report of the emergency use must be submitted to the IRB within 5 working days (ie, there is a requirement similar to the one that the sponsor report the use to FDA within 5 working days of learning of the use). The physician is responsible for ensuring that the proposed use is appropriate per the applicable regulations and that patient protection measures are followed. If it is anticipated that there will be a future need for use of the device at the institution, steps should be taken to obtain FDA and IRB approval for such use under the IDE.
Q: Is there a limit on the number of such cases one center can do before a formal IDE is required?
A: The guidance regarding the emergency use of an unapproved device states, “Subsequent use of the device in an emergency situation may not occur unless the physician or another person obtains approval of an IDE for the device and its use.” This is not meant to preclude an attempt to save the life of a desperately ill patient but rather to ensure that investigational devices are presented to FDA for review as early as possible and that appropriate clinical trials are initiated.
Q: Physicians involved in clinical trials have often established a reputation with their practice that involves the referral of the sickest and most complicated patients. Does the FDA allow liberal use of ?compassionate? use for these patients if the physician is already involved in the clinical trial of a given device or procedure?
A: The FDA does not differentiate between physicians in determining whether requests for compassionate uses should be granted or if emergency uses are appropriate. The determination is based on the situation for the specific patient. If the physician has many referrals as described in the question, the best option from a regulatory perspective would be to have an arm of an IDE study in place to allow for enrollment of the patients in a study, rather than obtaining separate approvals for the treatment of each patient or providing separate emergency use reports.
Dorothy B. Abel is a Regulatory Review Scientist with the US FDA Center for Devices and Radiological Health in Rockville, Maryland; she is also a regular columnist for Endovascular Today. Ms. Abel may be reached at (301) 443-8262, ext. 165; email@example.com.