Human Research Protection Program: Policy
Emergency Use of Test Articles
Adopted By: All Campus IRB
Adoption Date: August 4, 2005
Revised: December 4, 2008
Purpose: This document describes how
UW-Madison Institutional Review Boards (IRBs) assure compliance with federal
regulations governing the emergency use of an investigational or unlicensed
test article.
Definitions
I. Test article means any drug for human use, biological product
for human use, medical device for human use, human food additive, color additive,
electronic product, or any other article subject to regulation under the act or
under sections 351 or 354-360F of the Public Health Service Act. 21
CFR 56.102(l)]
II. Life-threatening, for purposes of 21
CFR 56.102(d) includes both life-threatening and severely debilitating
diseases or conditions:
A. 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 condition does not have to be immediately
life-threatening or to immediately result in death. Rather, the patient must be
in a life-threatening situation requiring intervention before review at a
convened meeting of the IRB is feasible.
B. Severely debilitating means diseases or conditions that cause major
irreversible morbidity. Examples include blindness, loss of arm, leg, hand or
foot, loss of hearing, paralysis or stroke.
Policy
I. UW-Madison complies with the FDA regulations
related to emergency use of test articles.
A. Emergency use of a test article without prior IRB approval.
1. The IRB expects to be notified, if at all
possible, before emergency use of a test article.
2. FDA regulations allow the emergency use of a test article without prior
IRB approval if the following conditions are met [21
CFR 56.104(c)]:
a. the
patient is in a life-threatening situation;
b. no
standard acceptable treatment is effective or available; and
c. there
is not sufficient time to obtain IRB approval. [21
CFR 56.102(d)]
3. In the case of an unapproved medical device,
the treating physician must obtain an independent assessment by an uninvolved
physician that the use is warranted and that there no other reasonable
alternatives are available.
5. Informed consent from the patient or the patient’s legally authorized
representative is required unless the conditions for exception are met [21
CFR 50.23]. [See, II.D, below]
6. In all cases, the emergency use must be
reported to the IRB within 5 business days following its use. [21
CFR 56.104(c)]
II. IRB Procedures for emergency use of a test article.
A. During normal business hours
1. The treating physician (or designee) generally contacts the IRB Office
and describes the potential use. The call is referred to the IRB Director (or
designee). In the case of an emergency use of an investigational drug or
biologic, the treating physician (or designee) also contacts the University of
Wisconsin Hospital and Clinics (UWHC) Pharmaceutical Research Center (PRC).
2. The treating physician (or designee) is asked to submit a formal,
signed letter or application for emergency use form that outlines the emergency
need for such treatment and that confirms that alternative treatments are
unavailable. A copy of the consent form to be used also is requested for
review. The Office of Clinical Trials is generally available to provide
administrative assistance to physicians who are considering the emergency use
of a test article and help facilitate interactions between the IRB, PRC, and
the treating physician. In the case of a device, the treating physician (or
designee) must also provide documentation from another physician who is not
part of the patient’s treatment team of his or her concurrence that the
emergency use is warranted and no alternative treatment available.
3. The IRB Director contacts the IRB Chair or another IRB member with
medical expertise to discuss the request and determine whether the use meets
the regulatory requirements allowing an exemption from IRB review, and that
informed consent will be obtained, or that the situation meets the requirements
allowing an exception from the requirement for informed consent.
4. If the IRB chair or member agrees that the use is warranted and
determines that the use meets the regulatory requirements allowing an exemption
from IRB review, and that informed consent will be obtained, or that the
situation meets the requirements allowing an exception from the requirement for
informed consent, a letter of acknowledgement is written, which expresses
concurrence with the use of the test article but acknowledges that IRB approval
has not been granted.
5. The original signed letter is then delivered to the treating physician
(or designee) with a copy sent to the UWHC PRC and another copy placed in the
IRB Office files.
6. If an emergency use of a test article occurred without submission of a
formal application for IRB review, the formal application, including the
consent form, must be submitted subsequently within the timeline designated by
the IRB, usually within 5 business days.
7. The report is reviewed at the next scheduled IRB meeting to determine
whether the use met the regulatory requirements allowing an exemption from IRB
review, and that informed consent was obtained, or that the situation met the
requirements allowing an exception from the requirement for informed consent.
If the IRB determines that the conditions for emergency use or informed consent
requirements were not satisfied, the event is handled under the noncompliance
policy.
B. Outside of normal business hours
1. If it is not possible for a treating physician (or designee) to inform
the IRB prior to the emergency use of a test article, the treating physician
(or designee) must report the emergency use of the test article to the IRB as
soon as possible, but no later than 5 business days from the date of use.
2. The report is reviewed at the next scheduled IRB meeting to determine
whether the use met the regulatory requirements allowing an exemption from IRB
review, and that informed consent was obtained, or that the situation met the
requirements allowing an exception from the requirement for informed consent.
If the IRB determines that the conditions for emergency use or informed consent
requirements were not satisfied, the event is handled under the noncompliance policy.
3. Even outside of normal business hours, a treating physician must inform
the PRC of any emergency use of a test article prior to such use.
C. Subsequent Uses
1. If the treating physician (or designee) expects to use the test article
in a subsequent patient, he or she must submit to the IRB a protocol requesting
multiple use of the test article.
2. Emergency treatment to a second individual will not be denied if the
only obstacle to the treatment is that the IRB has not had sufficient time to convene
a meeting to review the request.
D. Exception to Informed Consent Requirement in Emergency Situations
1. The treating physician (or designee) must obtain informed consent of
the patient or the patient's legally authorized representative unless either
the treating physician (or designee) and a physician who is not otherwise
participating in the clinical investigation certify in writing all of the
following [UWHC policy on use of investigational agent in emergency; 21
CFR 50.23 (a)]:
a. The patient is confronted by a life-threatening
situation necessitating the use of the test article.
b. Informed consent cannot be obtained because of
an inability to communicate with, or obtain legally effective consent from, the
patient.
c. Time is not sufficient to obtain consent from
the patient's legal representative.
d. No alternative method of approved or generally
recognized therapy is available that provides an equal or greater likelihood of
saving the patient's life.
2. If, in the opinion of the treating physician (or designee), immediate
use of the test article is required to preserve the patient's life, and if time
is not sufficient to obtain an independent physician's determination that the
four conditions above apply, the treating physician (or designee) should make
the determination and, within 5 business days after the use of the article,
have the determination reviewed and evaluated in writing by a physician who is
not participating in the clinical investigation.
3. The treating physician (or designee) must submit to the IRB the written
documentation supporting the exception to the informed consent requirement
within 5 business days after the use of the test article. [21
CFR 50.23 (c)]
4. The documentation is reviewed at the next scheduled IRB meeting to
determine whether the situation met the requirements allowing an exception from
the requirement for informed consent. If the IRB determines that the informed
consent requirements were not satisfied, the event is handled under the
noncompliance policy.
E. Emergency Use of a Test Article Prior to Submission of IND or IDE
1. The need for an investigational drug may arise
in an emergency situation that does not allow time for submission of an IND in accordance with 21
CFR 312.23 or 21
CFR 312.34. In such a case, the FDA may authorize shipment of the drug for
a specified use in advance of submission of an IND. A request for such authorization may be transmitted to
FDA by telephone or other rapid communication means. Except in extraordinary
circumstances, such authorization will be conditioned on the sponsor making an
appropriate IND
submission as soon as practicable after receiving the authorization. [21
CFR 312.36]. For additional information, see IRB Information Sheets--Drugs and
Biologics - Updated 9/98 [http://www.fda.gov/oc/ohrt/irbs/drugsbiologics.html#treatment]
2. The FDA allows the emergency use of an unapproved
medical device prior to submission of an IDE if the need arises in an emergency
situation that does not allow time for submission of an IDE in the usual
manner. For additional information, see GUIDANCE FOR EMERGENCY USE OF UNAPPROVED MEDICAL DEVICES
[http://www.fda.gov/cdrh/manual/unappr.html].
3. If the need to use a test article arises in an
emergency situation that does not allow time for submission of an IDE or IND in the usual manner, the
treating physician (or the physician’s designee) is required to make sure that
all FDA requirements are satisfied.
4. The exception to the requirement for informed
consent may apply if the need to use a test article arises in an emergency
situation that does not allow time for submission of an IDE or IND in the usual manner.
(See, Section II.D, above.)
