Exception from Informed Consent (EFIC) for Emergency Research

Exception from Informed Consent (EFIC), sometimes called the “emergency research exception,” is a narrow regulatory pathway that allows a clinical investigation of an FDA-regulated drug, biologic, or device to enroll subjects who cannot give informed consent because they are in a sudden, life-threatening emergency and no legally authorized representative (LAR) is reachable in time. It is codified at 21 CFR 50.24, within FDA’s human subject protection regulations (21 CFR Part 50), and has a closely related counterpart at 45 CFR 46.101(i), under which the HHS Secretary can waive the general Common Rule consent requirements for the same category of emergency research.

Why the exception exists

Standard research ethics, reflected in the Belmont Report and the Common Rule (45 CFR 46), treats prospective informed consent as the default safeguard for respect for persons. Some conditions — cardiac arrest, severe traumatic brain injury, hemorrhagic shock — leave no time to locate and counsel a subject or LAR before an intervention window closes, yet the population affected is precisely the one that stands to benefit most from evaluating an unproven or unsatisfactory-treatment intervention. Without a defined exception, this class of research would be effectively impossible to conduct under FDA-regulated protocols. EFIC exists to make that research possible while substituting a set of alternative, community-facing safeguards for the individual consent that cannot practically be obtained.

Operational definition: the 21 CFR 50.24 criteria

A study is only eligible for EFIC when the IRB and FDA are satisfied that all of the following conditions are met:

• Life-threatening situation, no satisfactory alternative. Subjects must be in a life-threatening condition for which available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence is necessary to determine the safety and effectiveness of the intervention being studied.
• Consent is not feasible. The subject’s condition requires intervention before consent from the subject or LAR can reasonably be obtained, and the window for effective treatment is so short that obtaining consent is not feasible — not merely inconvenient.
• No proven effective treatment exists that would make participation in the research inappropriate, and participation in the research holds out the prospect of direct benefit to the subject (based on the specific disease/condition, the risks and benefits of standard therapy versus the investigational intervention, and what is known about the risks and benefits of the test article itself).
• The research could not practicably be carried out without the waiver of informed consent — i.e., there is no feasible way to obtain scientifically valid data on this population and this condition while also obtaining prospective consent.
• Community consultation and public disclosure. Before the study begins, the investigator must consult with the communities in which the study will be conducted and from which subjects will be drawn, and must publicly disclose plans for the study and its risks/benefits. After the study concludes, results and the study’s outcome must also be publicly disclosed to the communities consulted.
• Independent oversight. An independent data monitoring committee must oversee the study, and additional protections defined by the IRB — such as an objective determination of the subject’s medical condition by an independent physician not otherwise involved in the study — are required.
• IRB approval of the full protocol, including the consent-exception justification and the community consultation/disclosure plan, is required before any enrollment under the exception can begin, and FDA involvement (concurrence and, in practice, close consultation) is expected for the exception to apply.

Once a subject or their LAR becomes reachable, consent for continued participation in the study must be sought as soon as feasible — EFIC covers only the initial emergency enrollment, not the remainder of the study. If consent is refused at that point, the subject’s data collected up to that point may still be used depending on the protocol and IRB determination, but no further study-related intervention occurs without consent.

Community consultation and public disclosure in practice

Community consultation is the safeguard that substitutes for individual consent under EFIC: instead of asking each prospective subject to agree in advance (which is by definition impossible), investigators are required to solicit and document the views of the population from which subjects will actually be drawn — typically the catchment area served by the participating emergency medical services and trauma or emergency-department sites. This can include public meetings, surveys, focus groups, and outreach through local media, and IRBs commonly require documentation of both the methods used and how community feedback shaped the protocol (for example, added exclusion criteria or an opt-out registry allowing individuals to pre-emptively decline participation if they are ever brought in unconscious). Public disclosure — distinct from consultation — is the requirement to make the study, its risks, and its purpose publicly known before enrollment starts, and again after the study ends to disclose results and outcomes to the same communities.

Worked example

A multicenter trial testing a novel hemostatic agent for patients presenting in hemorrhagic shock from trauma is a canonical EFIC scenario: patients typically arrive unconscious or too unstable to be approached for consent, no LAR is present or reachable within the treatment window, existing resuscitation options are unsatisfactory for the population being studied, and delaying the intervention to locate consent would itself be a life-threatening delay. The sponsor and sites would need to complete community consultation across the relevant emergency-catchment area, publicly disclose the study before enrollment, secure IRB and FDA sign-off on the full EFIC justification, and establish an independent data monitoring committee before any subject could be enrolled under the exception.

Counter-example

A trial enrolling stroke patients where family members are routinely present and reachable at the bedside within the eligibility window does not meet the EFIC “consent is not feasible” criterion, even though stroke is life-threatening and time-sensitive — if an LAR can, in practice, be reached and asked for consent before the intervention must occur, the study should pursue standard or streamlined LAR consent rather than the emergency exception. Similarly, research that is merely inconvenient to consent for (e.g., a busy emergency department with limited staff time), rather than genuinely infeasible within the clinical window, does not qualify.

Related concepts

• Informed consent — the general concept EFIC creates a narrow, tightly conditioned exception to.
• Informed Consent in Research: What It Requires and How It Works — the full requirements EFIC substitutes alternative protections for.
• When Should Informed Consent Be Obtained? Timing, Re-Consent, and the Emergency Exception — covers re-consent timing once a subject or LAR becomes reachable.
• 21 CFR Part 50 (Protection of Human Subjects) — the FDA regulation EFIC (50.24) sits within.
• Belmont Report and Common Rule (45 CFR 46) — the ethical and regulatory foundation EFIC departs from under defined conditions.
• Vulnerable Populations in Research — EFIC subjects are, by the nature of the emergency, unable to protect their own interests through ordinary consent.
• Risk-Benefit Analysis — the IRB determination that underpins the “prospect of direct benefit” criterion.