Emergency Use of FDA-Regulated Test Articles- PRO151   

PROCEDURE
 

Investigator Responsibilities

• Notifies the IRB Chair or OIRB Director (or designee) of the need for emergency use of an investigational test article.
• Creates a submission in IRAP, as time permits,  prior to use of an investigational test article for acknowledgement by the IRB Chair or designee, stating:
  • The subject is in an immediate serious or life-threatening condition that needs immediate treatment;
  • No generally acceptable alternative for treating the subject is available;
  • Because of the immediate need to use the drug, agent, biologic or device, there is no time to obtain convened IRB approval for the use;
  • The use will be reported to the OIRB within five working days; and
  • Any subsequent use of the test article at UAB will be subject to IRB review.

Note: Some manufacturers will agree to allow the use of the test article, but their policy requires an acknowledgement or “IRB approval letter” before the test article will be shipped.

• Contacts the IDE or HDE holder, if applicable. If none exists, contacts the FDA.
• Contacts the FDA to obtain an emergency use expanded access IND (see 21 CFR 312.210), if applicable.
• Obtains informed consent prior to use of the test article (see Basic Elements and Disclosures Included in Informed Consent for Emergency Use of Test Articles, below), unless
• The investigator and a physician unrelated to the investigation certify in writing to all of the following elements:
  • Subject is confronted with a life-threatening situation necessitating immediate use of the test article (drug or device);
  • Subject is unable to communicate or legally effective informed consent cannot be obtained;
  • Time is not sufficient to obtain informed consent from the subject’s LAR; and
  • No available alternative method or approved or generally recognized therapy exists that provides an equal or greater likelihood of saving the subject’s life.

OR

• If, in the opinion of the investigator, immediate use of the test article is required and there is not sufficient time to obtain the certification of an independent physician in advance of use of the test article, the investigator:
  • Certifies in writing the elements listed above; and
  • Has an independent physician review and evaluate the decision in writing within 5 working days after the use of the test article.
• Submits information to the IRB in writing within 5 working days of the emergency use of an investigational test article to qualify for exemption from prior IRB review and approval. This includes individual patient expanded access IND applications for emergency use.  The submission should include the following information:
  • Description of the life-threatening situation that required immediate intervention with the use of the test article;
  • What the known or foreseeable risks were of the intervention and anticipated benefits of the intervention;
  • A copy of the signed informed consent document if consent was obtained. If not, copies of the certifications the by the investigator and a physician unrelated to the investigation addressing the items above if obtaining informed consent was not feasible;
  • Name of the investigational drug, agent, biologic, or device used;
  • Letter of authorization from the sponsor/manufacturer obtaining their agreement to provide expanded access to the investigational drug;
  • Documentation of FDA authorization for the expanded access use;
  • Description of the treatment plan in sufficient detail for IRB review;
  • Any reportable problems described under POL006 UAB Policy to Ensure Prompt Reporting of Unanticipated Problems Involving Risks to Subjects or Others to the IRB;
  • Outcome, if known; and Assessment of the likelihood of a similar need for the investigational or unlicensed test article and, if likely, immediately initiates the process to obtain an IND or IDE and convened IRB approval.
• Cannot include the data on a recipient of emergency medical care with an FDA-unapproved test article for a prospectively conducted research activity;
• Notifies designated officials at performance sites, as applicable.

OIRB Responsibilities

Reviewing Staff:

• Contacts the IRB Chair or designee about the notification for emergency use.
• Reviews with the investigator the information needed for acknowledgement of the use from the IRB Chair and submission to qualify for exemption from IRB requirements;
• Informs the investigator when the IRB Chair has reviewed and approved the emergency use;
• Refers all materials submitted for acknowledgement and exemption from IRB requirements to the IRB Chair for review.
• Schedules acknowledged emergency use exemptions are scheduled for review at the next available convened IRB meeting.
• Gives all documents related to the emergency use to administrative staff for filing and distribution at the next available convened IRB meeting.

IRB Responsibilities

IRB Chair or designee:

• Provides verbal acknowledgement that the situation meets the regulatory requirements for emergency use;
• Reviews written information for emergency use of an investigational test article and provides concurrence with the emergency use.
• Reviews materials submitted by investigator within 5 days of emergency use to qualify for exemption from IRB requirements.
• Concurs with emergency use when submission for exemption is timely and information meets criteria for IRB exemption for emergency use.
• Refers submissions to convened IRB using POL028 UAB Policy on Compliance with Human Subjects Regulations or IRB Requirements or Determinations when submission is either untimely (>5 days after use) or does not support a finding that the criteria are met to qualify for exemption.
• May request additional information before issuing a concurrence.
• Returns materials to management staff for inclusion on the agenda of the next convened IRB meeting.
• Presents the emergency use information to the convened IRB.

Each IRB member assigned to a convened IRB meeting in which emergency use exemption has been granted receives and reviews the emergency use materials supplied with the agenda in enough depth to discuss at the meeting.

The IRB confirms the emergency use concurrence by the IRB Chair.

Basic Elements and Disclosures Included in Informed Consent for

Emergency Use of Test Articles

• An explanation of the purpose of the use of an FDA-unapproved test article;
• The expected duration of the use of the test article;
• A description of the procedures to be followed;
• Identification of any procedures that are experimental;
• A description of any reasonably foreseeable risks or discomforts to the recipient;
• A description of any benefits to the recipient or to others which may reasonably be expected;
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the recipient (If appropriate alternatives exist, the emergency use is not warranted.);
• A statement describing the extent, if any, to which confidentiality of records identifying the recipient will be maintained and noting that the FDA may inspect the records;
• For procedures involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what it consists of, or where further information may be obtained;
  • The UAB injury compensation clause must be included and states, “UAB has made no provisions for monetary compensation in the event of injury resulting from the use of the test article, and in the event of such injury, treatment is provided, but is not free of charge.”
  • If the manufacturer will not provide any compensation for injuries related to the use of the test article, then include in the UAB injury compensation clause, “UAB and [name of manufacturer] have made no provisions for monetary compensation….”
• A statement that the test article being supplied would only be administered within the context of a research protocol if the emergency situation at hand did not exist;
• An explanation of whom to contact for answers to pertinent questions about the procedures and recipients’ rights and whom to contact in the event of an injury related to the test article;
• A statement that agreement to the emergency use of the test article is voluntary, refusal of the use of the test article will involve no penalty or loss of benefits to which the recipient is otherwise entitled, and the recipient may discontinue participation at any time without penalty or loss of benefits to which the recipient is otherwise entitled.

Additional Elements, When Appropriate

When appropriate, one or more of the following elements of information will be provided to each recipient:

• A statement that significant new findings that may relate to the recipient’s willingness to continued use of the test article will be provided to the recipient. The IRB generally requires this element unless good reasons are provided to exclude it.
• A statement that the particular treatment or procedure may involve risks to the recipient, which are currently unforeseeable (or to the embryo or fetus, if the recipient is or may become pregnant).
• Anticipated circumstances under which the recipient’s participation may be terminated by the investigator without regard to the recipient’s consent. Examples of when the IRB requires this element are:
  • At the investigator’s discretion;
  • If the investigator determines it is in the best interest of the recipient;
  • If the recipient does not follow the investigator’s instructions.
• Any additional costs to the recipient that may result from the use of the test article. Examples of when the IRB requires this element are:
  • If procedures result in potential billing to the recipient or third-party payers;
  • If recipients may have out-of-pocket costs (e.g., parking, meals, transportation).
• The consequences of a recipient’s decision to withdraw and procedures for orderly termination by the recipient. Examples of when the IRB requires this element are:
  • If drug dose tapering is required and has risks to the recipient.
• A statement describing the approximate number of individuals who have previously received the test article. If none, an explanation of any relevant animal data and their significance.
• Any other information required to be disclosed under federal, state, or local law.