3.3 Informed Consent in Special Circumstances & Exceptions

3.3 Informed Consent in Special Circumstances & Exceptions

While obtaining prospective, written informed consent is the standard requirement for all human subject research, the Food and Drug Administration (FDA) and Department of Health and Human Services (HHS) recognize that certain emergency situations and clinical realities require exceptions. These special circumstances are highly regulated under 21 CFR Part 50 to prevent abuse while allowing critical, life-saving research to proceed.

Exception for Individual Subjects in Life-Threatening Situations (21 CFR 50.23)

This exception allows an investigator to use an investigational drug, device, or biologic on an individual subject in a life-threatening emergency without obtaining prior informed consent.

Criteria for the Exception

To invoke this exception, both the clinical investigator and an independent physician (who is not otherwise involved in the clinical investigation) must certify in writing all of the following:

1. The subject is in a life-threatening situation, necessitating the immediate use of the test article.
2. The subject is unable to communicate, and legally effective consent cannot be obtained.
3. Time is insufficient to obtain consent from the subject's Legally Authorized Representative (LAR).
4. No alternative method of approved or generally recognized therapy is available that provides an equal or greater likelihood of saving the subject's life.

Submission Timeline and Rules

If time permits, this written certification must be reviewed and approved by the Institutional Review Board (IRB) before using the test article. However, if the investigator determines that immediate use is required to save the subject's life, and there is insufficient time to obtain the independent physician's opinion beforehand, the investigator may use the test article. In this scenario, the investigator must have an independent physician evaluate the use and submit a joint written report to the IRB within 5 working days after the use of the test article.

Exception for Planned Emergency Research (21 CFR 50.24)

Unlike the individual exception under 21 CFR 50.23, 21 CFR 50.24 permits a waiver of informed consent for an entire clinical investigation (planned emergency research). This applies to trials evaluating interventions for acute, life-threatening conditions (e.g., cardiac arrest, traumatic brain injury) where subjects are suddenly incapacitated and cannot provide consent, and their LARs are not readily available.

Criteria for IRB Approval of Planned Emergency Research

An IRB may approve such a study without requiring informed consent from all subjects if it finds and documents the following:

1. The subjects are in a life-threatening situation, and available treatments are unproven or unsatisfactory.
2. Obtaining informed consent is not feasible because the subject is unconscious or incapacitated, and the intervention must be administered before consent can be obtained from an LAR.
3. Participation holds out the prospect of direct benefit to the subjects.
4. The research could not practicably be carried out without the waiver.
5. The sponsor has obtained an Investigational New Drug (IND) or Investigational Device Exemption (IDE) from the FDA.

Community Consultation and Public Disclosure

A unique and strict requirement of 21 CFR 50.24 is the mandate for community consultation and public disclosure:

• Community Consultation: The sponsor/investigator must consult with representatives of the community in which the research will be conducted (e.g., town halls, focus groups) to discuss the study, its risks, and the waiver of consent before the study begins.
• Public Disclosure: Prior to starting the study, the investigator must publicly disclose the research plans and risks to the community. Furthermore, after the trial is completed, the investigator must publicly disclose the results of the study, including the demographic characteristics of the participants, to the community.
• Opt-Out Mechanism: When feasible, the investigator must establish a way for community members to opt out of the study (e.g., wearing a specific bracelet indicating they do not wish to participate in the emergency research).

Military Exceptions (21 CFR 50.23(d))

Under specific circumstances, the prior consent requirement may be waived for administration of an investigational drug, device, or biologic to a member of the U.S. Armed Forces.

• Authority: This waiver can only be granted by the President of the United States.
• Process: The Secretary of Defense must request the waiver, and the FDA Commissioner must determine that obtaining consent is not feasible, is contrary to the health and safety of the service members, or is contrary to national security interests. This is typically invoked in connection with specific combat operations or threat of exposure to biological/chemical warfare agents.

The Short Form Consent Process (21 CFR 50.27(b)(2))

The short form process is a regulatory mechanism designed to enroll subjects who are unable to read English (Limited English Proficiency [LEP] subjects) when a fully translated version of the IRB-approved consent form is not immediately available. It should not be used as a routine method; if a site frequently enrolls subjects of a specific language, the IRB will require a fully translated consent form.

Essential Components of the Short Form Process

The process requires three distinct roles and two separate documents:

• Required Documents:

  1. Short Form Consent Document: A brief written document in the subject's native language stating that the basic elements of informed consent have been presented orally to the subject or their LAR.
  2. Written Summary: A detailed written summary of the oral presentation (typically, the full English consent form serves as this summary).
  3. IRB Approval: Both the short form and the summary must be pre-approved by the IRB.

• Process Requirements:

  1. An interpreter must be present to translate the oral presentation of the summary.
  2. An impartial witness (who is fluent in both English and the subject's language, and is not a member of the study staff) must be present to witness the entire oral presentation. The interpreter can serve as the witness if they meet the criteria of being impartial.
  3. Signatures:
     • The subject or LAR signs and dates the short form document.
     • The witness signs and dates both the short form and the summary.
     • The person obtaining consent (investigator/coordinator) signs and dates the summary.
     • A copy of both the signed short form and the signed summary must be given to the subject or their LAR.

Translation Requirements for Non-English Speakers

To ensure that non-English speaking subjects are fully informed, the following rules apply:

• IRB Review: All translated consent forms, short forms, and recruitment materials must be reviewed and approved by the IRB before they are used with subjects.
• Qualified Translators: Translations should be conducted by qualified individuals (such as certified translation services). The IRB typically requires a certificate of translation or a back-translation (translating the document back into English by a different translator) to verify accuracy.
• Family Members: Family members of the subject should never serve as the official interpreter or witness during the consent process. They may lack understanding of complex medical terms, or their presence may introduce subtle coercion or conflicts of interest.