Exception from Informed Consent Requirements for Emergency Research
This guidance assists Institutional Review Boards (IRBs), clinical investigators and sponsors in conducting emergency research under an exception from informed consent requirements (21 CFR 50.24). It applies to investigations involving human subjects who have a life-threatening medical condition that necessitates urgent intervention, cannot provide informed consent due to their condition, and where available treatments are unproven or unsatisfactory.
Recommended Actions
- Establish and document therapeutic window based on scientific evidence
- Develop comprehensive plan for:
- Community consultation activities
- Public disclosure before and after study
- Contacting legally authorized representatives
- Informing subjects/representatives about participation
- Submit separate IND/IDE application clearly identifying exception from informed consent
- Establish independent data monitoring committee for study oversight
- Create procedures for:
- Documenting attempts to contact representatives
- Allowing discontinuation of participation
- Maintaining required records
- Reporting study results
- Obtain IRB review and approval of:
- Study protocol
- Informed consent procedures/documents
- Community consultation plans
- Public disclosure plans
- Monitor and document:
- Community consultation activities
- Public disclosure activities
- Contact attempts with representatives
- Study conduct and safety
- Report results through:
- Public disclosure
- Clinical trial registration
- FDA submissions
- Scientific publications
Key Considerations
Clinical testing
- Must demonstrate prospect of direct benefit to subjects
- Must be conducted under separate IND/IDE
- Phase 1 studies generally not appropriate under this exception
- Non-inferiority trials may be acceptable if they meet regulation requirements
- Must establish independent data monitoring committee for oversight
Non-clinical testing
- Must have appropriate animal and preclinical data supporting potential benefit
- Must demonstrate reasonable risk-benefit ratio based on available evidence
Human Factors
- Must document why obtaining informed consent is not feasible
- Must attempt to contact legally authorized representative within therapeutic window
- Must provide opportunity for family members to object to participation
- Must inform subjects/representatives at earliest feasible opportunity about participation
Safety
- Must establish therapeutic window based on scientific evidence
- Must have procedures to protect subject rights and welfare
- Must have procedures for informing subjects/representatives about participation
- Must allow discontinuation of participation without penalty
Other considerations
- Must conduct community consultation before study initiation
- Must provide public disclosure before and after study completion
- Must document IRB findings and determinations
- Must maintain records for at least 3 years after study completion
- Must report study termination/discontinuation to FDA
Relevant Guidances
- Early Collaboration Meetings for Medical Device Development: Determination and Agreement Procedures
- Early Feasibility Medical Device Clinical Studies Including First in Human (FIH) Studies
- Design Considerations for Medical Device Pivotal Clinical Studies
- Informed Consent in Clinical Investigations: Requirements, Documentation, and Procedures
- Continuing Review of Clinical Investigations by Institutional Review Boards (IRBs)
- IRB Responsibilities for Reviewing Investigator Qualifications, Research Sites, and IND/IDE Requirements
Related references and norms
- ICH E6: Good Clinical Practice
- ICH E10: Choice of Control Group and Related Issues in Clinical Trials
Original guidance
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