Purpose: These policies and procedures are applied by UW-Madison Institutional Review Boards (IRBs) in authorizing the use of a Humanitarian Use Device (HUD) for treatment or research.
Policy:
I. Definition of a HUD
A HUD is a device that is intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer then 4,000 individuals in the United States per year. [21 CFR Part 814, Subpart H]
II. HDE Application
A HUD is approved for marketing through a humanitarian device exemption (HDE) application filed in accordance with the requirements of the Federal Food, Drug and Cosmetic Act (Act). [21 CFR Part 814, Subpart H] An HDE application is similar to a premarket approval application (PMA) but is exempt from the “effectiveness” requirements of a PMA in order to encourage the discovery and use of devices to treat rare conditions or diseases.
An approved HDE authorizes marketing of the HUD for clinical use; however, clinical use of the device is limited to the indication specified in the product labeling.
III. IRB Approval
Under the Act, a HUD may be used only after IRB review and approval. If the health care provider is seeking to use the HUD for treatment and not research, the health care provider should submit an Application for Treatment of Patients with a HUD. See, HUD Form (Document 148). If the health care provider seeks to use the HUD as part of a clinical investigation or research project designed to obtain data to support a PMA, an Application for Initial Review Form (Document 157) must be filed.
The initial review must be performed by the full IRB, but continuing review may be done on an expedited basis.
The IRB must ensure that the proposed use is within the FDA-approved indication and that the use of the device does not exceed the scope of the FDA’s approval. After an IRB approves the use of the HUD, if the FDA approves use of the HUD for additional clinical indications, IRB approval is required before the HUD can be used for these additional indications.
Each individual use of the HUD may not need IRB review and approval. Instead, as long as use of the HUD is within the FDA approved indication, the IRB may approve use of the device without further restrictions, on a case by case basis, or use of the device under a protocol.
The health care provider is notified in writing of the IRB’s decision.
IV. Conflict of Interest
Only if the HUD is being used in research, i.e., to support a PMA, will the IRB review the health care provider’s conflict of interest disclosure form at the time of initial review.
V. Informed Consent
Because the HDE provides for marketing approval, use of the HUD is generally considered as treatment and not research, and the health care provider is generally not required to obtain informed consent to participate in a research protocol from the patient. However, the IRB can require the health care provider to obtain informed consent for research participation if it so chooses.
Although informed consent to participate in research may not be required, Wisconsin state law, which requires a health care provider to obtain informed consent of a patient for medical diagnosis or treatment, does apply.
If the HUD is the subject of a clinical investigation in which safety and efficacy data is being collected to support a PMA, informed consent to participate in research is required.
VI. HIPAA and Protected Health Information
Because use of a HUD is generally not research, a HIPAA authorization for research using protected health information would generally not be required from the patient. However, the general HIPAA requirements governing the use or disclosure of patient health information do apply.
HIPAA authorization for research is required if use of the HUD is in the context of a clinical investigation to obtain safety and efficacy data to support a PMA.
VII. Modifications in HUD
If there are any modifications to the HUD or the clinical use of the HUD after IRB approval, the health care provider must report these changes to the IRB promptly by following the IRB policy and procedures for amendments to protocols. [See, Section X.F, below]
VIII. Emergency Use of HUD
A HUD may be used off-label in an emergency situation, but the health care provider should follow the same procedures governing emergency uses of unapproved devices. 21 CFR 814.124; Humanitarian Device Exemptions (HDE) Regulation: Questions and Answers; Final Guidance for Industry [http://www.fda.gov/cdrh/ode/guidance/1381.html].
Under the Emergency Use Policy, the following conditions should exist for a situation to be considered an emergency: (1) the patient is in a life threatening condition that needs immediate treatment; (2) no generally acceptable alternative for treating the patient is available; and (3) because of the immediate need to use the device, there is no time to use existing procedures to get FDA approval of the use. The health care provider should also obtain, if time permits, an independent assessment of the situation by an uninvolved physician that the use of the HUD is appropriate, concurrence from the IRB that the use meets the above stated conditions, and informed consent from the patient or the patient’s representative. The emergency use of the HUD should be reported to the full IRB and to the holder of the HDE (who must report the use to the FDA) within five (5) working days.
IX. Compassionate Use of HUD
A compassionate use of a HUD arises when a health care provider wishes to use a HUD off-label because no other alterative exists for the patient’s condition, but the situation is not an emergency. Before using a HUD on a compassionate use basis, the health care provider must obtain IRB approval of a protocol covering such use of a device and the informed consent of the patient or the patient’s representative. Additionally, the health care provider should provide the following information to the holder of the HDE, who would then submit an HDE amendment for FDA approval prior to the use: (1) a description of the patient’s condition; (2) the circumstances necessitating treatment with the HUD; (3) a discussion of why alterative therapies are unsatisfactory; and (4) information to address the patient protection measures (i.e. IRB approval, informed consent, etc.). Humanitarian Device Exemptions (HDE) Regulation: Questions and Answers; Final Guidance for Industry [http://www.fda.gov/cdrh/ode/guidance/1381.html].
X. Reporting Requirements
A. Unanticipated Adverse Device Effect. Under the Act, a health care provider using a HUD must submit to the sponsor of the device and the IRB any unanticipated adverse device effect within 10 working days of the health care provider first learning of the effect.
B. Serious Injury. A user facility of a HUD that receives or otherwise becomes aware of information from any source that reasonably suggests that a HUD has or may have caused or contributed to the serious injury of a patient must report such findings to the device manufacturer within 10 working days after becoming aware of the injury. If the manufacturer is unknown, the report must be made to the FDA.
C. Death. A user facility of a HUD that receives or otherwise becomes aware of information from any source that reasonably suggests that a HUD has or may have caused or contributed to the death of a patient must report such findings to the FDA and to the device manufacturer, if known, within 10 working days after becoming aware of the death.
D. Emergency Use. [See, Section VIII, above.] The emergency use of the HUD should be reported to the full IRB and to the holder of the HDE (who must report the use to the FDA) within five (5) working days.
E. FDA Actions. The health care provider should promptly report any FDA actions regarding the HUD to the IRB.
F. HUD Modifications. [See, Section VII, above.] Modifications to the HUD or the clinical use of the HUD should be promptly reported to the IRB in accordance with the IRB policy for amendments to protocols.
G. Withdrawal of IRB Approval. The health care provider using a HUD under IRB approval must promptly notify the FDA of IRB withdrawal of approval for the HUD. Additionally, the holder of an HDE must notify the FDA of the withdrawal of IRB approval within 5 working days after being notified of the withdrawal.