GUIDELINES FOR EMERGENCY TREATMENT INVOLVING INVESTIGATIONAL DRUGS, DEVICES OR BIOLOGICS

Emergency Treatment is not included in “Research” Data

Federal regulations in the protection of human subjects do not permit research activities to begin without prior IRB review and approval.  These regulations, however, do not limit or interfere with the authority of a physician to provide emergency medical treatment for patients, subject to FDA requirements for release and emergency use of an unapproved drug, biologic, or device on a single patient.

When emergency treatment is initiated without prior IRB review and approval, the patient data may not be included as research data in a prior or subsequent IRB-approved project. 

FDA Regulation of Emergency Use

The emergency use provision in the FDA regulations is an exemption from prior review and approval by the IRB of a single patient use of a drug, device, or biologic considered to be investigational.  The emergency use exemption of an investigational drug, biologic or device is permitted only if each of the following conditions exists as outlined in 21 CFR 56.102(d):

• A life-threatening or severely debilitating situation exists necessitating the use of the investigational drug, biologic or device;

• No standard acceptable alternative treatment is available; and

• Because of the immediate need to use the drug, biologic or device, there is not sufficient time to use existing procedures to obtain IRB approval for the use.

For purposes of this section, the following terms have the following meanings:

“Emergency use” of an investigational drug, biologic or deviceis defined as the use of an investigational article with a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain approval from the IRB.

“Life-threatening”means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival.  The criteria for life threatening do not require the condition to be immediately life threatening or to immediately result in death.  Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.

“Severely debilitating,"means diseases or conditions that cause major irreversible morbidity.  Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

The FDA regulations do not provide for expedited IRB approval in emergency situations. An IRB must either convene or give “full board” approval of the emergency use or, if the conditions of 21 CFR 56.102(d) are met and it is not possible to convene a quorum within the time available, the use may proceed without any IRB approval. 

Some manufacturers will agree to allow the use of the test article, but their policy requires “an IRB approval letter” before the test article will be shipped.  If it is not possible to convene a quorum of the IRB within the time available, the IRB may send the sponsor a written statement that the IRB is aware of the proposed use and considers the use to meet the requirements of 21 CFR 56.104(c).  Although this is not an “IRB approval”, the acknowledgement letter has been acceptable to manufacturers and has allowed the shipment to proceed.

Patient Consent in an Emergency

Even in an emergency use situation, the Principal Investigator is required to obtain informed consent to the treatment from the patient or the patient’s legally authorized representative (as specified under State law) unless both the Principal Investigator and an independent physician certify in writing that all of the following conditions exist:

• The patient is confronted by a life-threatening situation necessitating the use of the investigational drug, biologic or device;

• Informed consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the patient;

• Time is not sufficient to obtain consent from the patient’s legal representative; and

• No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the life of the patient.

If time is not sufficient to obtain the determination by an independent physician, the determination should be obtained within 5 working days after the use of the investigational article and be reported to the IRB within 5 working days.  See Emergency Use Consent form and Notification of Emergency Use of Investigational Drug or Device form .

D. Informing the IRB of Emergency Use

Principal Investigators are required to submit a written report on the emergency use to the IRB and to the applicable hospital administration within five (5) working days. However, this notification should not be construed as an IRB approval.  If the subject’s consent was not obtained prior to the emergency use, the written report must include a written determination by a non-participating staff physician that the four conditions specified in Section C above are met.  The report is reviewed by the Chair to ensure that the emergency use meets the applicable regulations.  The Principal Investigator is informed that if he/she anticipates the need to use the investigational article in additional subjects, prior review and approval by the IRB is required.  See Notification of Emergency Use of Investigational Drug or Device form .

The emergency use exception form prior IRB review is intended for one emergency use.  If the physician determines that a similar future need for the drug or biologic is likely, the physician should immediately initiate efforts to obtain IRB approval and an approved IND for the drug’s subsequent use. 

In addition, if an Investigational Device Exemption (IDE) for the device exists, the Principal Investigator must notify the sponsor of the emergency use.  If an IDE did not exist, the Principal Investigator must notify the FDA of the emergency use and provide the FDA, with a copy to the IRB, of a written summary of the conditions constituting the emergency, subject protection measures and results. 

If a Humanitarian Use Device (HUD) is used in an emergency use, the physician should devise a plan for monitoring the patient based on the specific needs of the patient and the limited information on the device and provide a follow-up report to the holder of the Humanitarian Device Exemption (HDE) on the patient’s condition and information regarding the patient protection measures.  The HDE holder submits this information to FDA as an HDE report.