Waiver to Informed Consent Process in Research Planned for Emergency Settings- PRO119   

procedure
 

Investigator Responsibilities

• Submits a completed IRB Application eForm (FOR200) to the IRB for review with the following information:
  • A rationale for the requirements in 21 CFR 50.24(a)(1)-(4) in POL019 Attachment A: Emergency Research Consent Waiver and/or HHS Emergency Research Consent Waiver (61 Fed. Reg. 51531, Oct. 2, 1996).
  • Definition of the length of the therapeutic window and the scientific evidence for its basis as proposed in the investigational plan or research protocol.
  •  A commitment to attempt to contact within the therapeutic window a legally authorized representative (LAR) for each subject when informed consent by the subject is not feasible or, if subject consent is feasible, asking the LAR for consent  rather than proceeding without consent.
  • A commitment to attempt to contact within the therapeutic window the subject’s family member who is not a LAR, when informed consent by the subject is not feasible and the LAR is not reasonably available, asking if the family member objects to the subject's participation in the study.
  • Proposed procedures for:
    • Obtaining informed consent from subjects or their LAR in situations where use of such procedures and documents is feasible;
    • Providing an opportunity for a family member to object to a subject’s participation in the clinical investigation or research;
    • Informing, at the earliest feasible opportunity, each subject—or if the subject remains incapacitated, a LAR of the subject, or if a LAR is not available, a family member—of the subject’s inclusion in the research, the details of the research and other information contained in the informed consent document;
    • Informing, as soon as possible, the subject or the subject’s LAR about the trail and obtaining consent to continue and other consent as appropriate when ICH-GCP (E6) applies (see GUI341);
    • Informing the subject—or if the subject remains incapacitated, a LAR of the subject, or if such a LAR is not reasonably available, a family member—that (s)he may discontinue the subject’s participation at any time without penalty or loss of benefits to which the subject is otherwise entitled;
    • Informing the subject about the research as soon as feasible;
    • Providing information about the research to the subject’s LAR or family member, if feasible, in the event the subject is entered into research with waived consent and the subject dies before a LAR or family member can be contacted;
  • Description of the proposed additional protections of the rights and welfare of the subjects for the study; and
  • Plan for tracking and summarizing all attempts to obtain informed consent from LAR and family members and making this information available to IRB at continuing review.
• Submits informed consent documents to be used with subjects and LAR in situations where informed consent process is feasible (see POL013 policy on, PRO113 procedure for informed consent process).
• Submits information to be used when providing a family member an opportunity to object to a subject’s participation.
• For FDA-regulated research, provides IND or IDE number and holder for protocols that clearly identify the protocol as one that may include subjects who are unable to consent.
• Provides a summary of all efforts to obtain informed consent from subjects’ LAR and family members at the time of continuing review.

IRB Responsibilities

For research subject to FDA regulations:

• Approves the activity and a waiver of informed consent process requirements at 45 CFR 46.116(e), (f) and 46.408, if applicable.
• The IRB with the concurrence of a licensed physician who is a member of or consultant to the IRB and who is not otherwise participating in the clinical investigation finds and documents each of the following: 
  • The research activity is subject to FDA Regulations (21 CFR Part 50) and will be carried out  under an FDA investigational new drug application (IND) or an FDA investigational device exemption (IDE).
  • The application clearly identifies the protocol will include participants who are unable to consent.
  • The research participants are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence, which might include evidence obtained through randomized placebo-controlled investigations, is necessary to determine the safety and effectiveness of particular interventions.
  • Obtaining consent is not feasible because:
    • The participants will not be able to give their consent as a result of their medical condition.
    • The intervention under investigation must be administered before consent from the participants’ legally authorized representatives is feasible.
    • There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical investigation.
  • Participating in the research holds out the prospect of direct benefit to the participants because:
    • Participants are facing a life-threatening situation that necessitates intervention.
    • Appropriate animal and other preclinical studies have been conducted, and the information derived from those studies and related evidence supported the potential for the intervention to provide a direct benefit to the individual participants.
    • Risks associated with the investigation are reasonable in relation to what is known about the medical condition of the potential class of participants, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.
  • The clinical investigation could not practicably be carried out without the waiver.
  • The proposed investigational plan defines the length of the potential therapeutic window based on scientific evidence, and the researcher has committed to attempting to contact a legally authorized representative for each participant within that window of time and, if feasible, to asking the legally authorized representative contacted for consent within that window rather than proceeding without consent.
  • The IRB has reviewed and approved consent procedures and a consent document consistent with 21 CFR 50.25. These procedures and the consent document are to be used with participants or their legally authorized representatives in situations where use of such procedures and documentation is feasible.
    • The IRB has reviewed and approved procedures and information to be used when providing an opportunity for a family member to object to a participant’s participation in the clinical investigation consistent with the FDA requirements for emergency research under 21 CFR 50.24.
  • Additional protections of the rights and welfare of the participants will be provided including, at least:
    • Consultation (including, where appropriate, consultation carried out by the IRB) with representatives of the communities in which the clinical investigation will be conducted and from which the participants will be drawn.
    • Public disclosure to the communities in which the clinical investigation will be conducted and from which the participants will be drawn, prior to initiation of the clinical investigation, of plans for the investigation, and  its risks and expected benefits.
    • Public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study, including the demographic characteristics of the research population, and its results.
    • Establishment of an independent data monitoring committee to exercise oversight of the clinical investigation.
  • The research activity has a separate IND or IDE which clearly identifies that the protocol(s) would include subjects who are unable to consent; and
  • With concurrence of a licensed physician member or consultant unaffiliated with the investigation, the requirements for an exception to informed consent process for research in emergency circumstances are met in relation to the protocol(s) (21 CFR 50.24(a),(b)).

• Determines it is unable to approve the activity because the activity does not meet the criteria for exemption provided in 21 CFR 50.24(a) or for other relevant ethical concerns:
  • Documents these findings; and
  • Provides the findings promptly to the clinical investigator and sponsor. Retains the IRB determinations and documentation related to the investigation for at least 3 years after completion of the investigation and makes the records accessible to FDA for inspection and copying.

For research subject to DHHS regulations: When research is not subject to FDA regulations, but follows DHHS regulations, the IRB finds, documents, and reports to DHHS that the following conditions have been met relative to the research:

• Obtaining consent is not feasible because:
  • There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical investigation.
• Participating in the research holds out the prospect of direct benefit to the participants because:
  • Participants are facing a life-threatening situation that necessitates intervention.
  • Appropriate animal and other preclinical studies have been conducted, and the information derived from those studies and related evidence supported the potential for the intervention to provide a direct benefit to the individual participants.
  • Risks associated with the investigation are reasonable in relation to what is known about the medical condition of the potential class of participants, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.
• Additional protections of the rights and welfare of the participants will be provided including, at least:
  • Consultation (including, where appropriate, consultation carried out by the IRB) with representatives of the communities in which the clinical investigation will be conducted and from which the participants will be drawn.
  • Public disclosure to the communities in which the clinical investigation will be conducted and from which the participants will be drawn, prior to initiation of the clinical investigation, of plans for the investigation, and  its risks and expected benefits.
  • Public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study, including the demographic characteristics of the research population, and its results.
  • Establishment of an independent data monitoring committee to exercise oversight of the clinical investigation.
    • If a participant is entered into research with waived consent and the participant dies before a legally authorized representative or family member can be contacted, information about the research is provided to the participant’s legally authorized representative or family member, if feasible. For the purposes of this waiver “family member” means any one of the following legally competent persons: Spouse; child, sibling, parent, grandparent, or grandchild. This includes stepparents, stepchildren, stepsiblings, and adoptive relationships.

• Approves the activity and a waiver of informed consent process requirements at 45 CFR 46.116(e), (f) and 46.408, if applicable;
• Approves the activity and a waiver of informed consent process requirements under ICH-GCP (E6) guidelines, if applicable (see GUI341);
• Finds and documents that the research is not subject to FDA regulations at 21 CFR Part 50; and
• Finds, documents, and reports to OHRP that the conditions in HHS Emergency Research Consent Waiver Section (b) are met.

OIRB Responsibilities

Reviewing Staff:

• Works with investigator to obtain necessary information for protocol review.
• Assists investigator with arrangement of consultation with community representatives about proposed conduct of the clinical investigation, when appropriate.
• Tracks findings and determinations of IRB to ensure satisfaction of federal requirements.
• Reviews communications to the investigators of the IRB findings.
• Reviews the minutes of the IRB meeting to assure sufficient information is included to meet the DHHS and FDA regulatory requirements.
• Reviews and approves letters to OHRP to report IRB approval of Waiver to Informed Consent Process in Research Planned for Emergency Settings.

Administrative Staff:

• Drafts communications to the investigators of the IRB findings and determinations.
• Sends communications to the investigators and sponsor when necessary.
• Prepares the minutes of the IRB meeting, including the necessary information to document the IRB findings and determinations to meet DHHS and FDA regulatory requirements.
• Drafts letters to OHRP to report IRB approval of Waiver to Informed Consent Process in Research Planned for Emergency Settings. 
• Sends letters to OHRP to report IRB approval of Waiver to Informed Consent Process in Research Planned for Emergency Settings for research not under FDA regulation.

Sponsor Responsibilities

For research regulated by the FDA:

• Promptly reports a determination that the IRB is unable to approve the research because it finds that the activity does not meet the criteria in the exception provided under 21 CFR 50.24(a) or other relevant ethical concerns to:
  • The FDA;
  • Other clinical investigators participating or asked to participate in this research or a substantially equivalent research study; and
  • Other IRBs that have been asked to review this research or an equivalent research study.