Waiver of Informed Consent (45 CFR 46.116(f))

A waiver of informed consent is an Institutional Review Board (IRB) determination, made under 45 CFR 46 section 46.116(f), that a study may proceed — including enrolling subjects or using their identifiable private information or identifiable biospecimens — without obtaining informed consent at all. It is the mechanism most commonly invoked for retrospective chart-review studies and secondary-database research, where the exposure or outcome of interest already occurred and re-contacting every prior subject is not practicable.

The five-part test under 46.116(f)(3)

Since the 2018 revised Common Rule, an IRB may approve a full waiver or alteration of consent only after finding — and documenting — that all five of the following are satisfied:

• Minimal risk. The research involves no more than minimal risk to subjects.
• Not practicable without the waiver. The research could not practicably be carried out without the waiver or alteration.
• Not practicable without identifiable data, if used. If the research involves identifiable private information or identifiable biospecimens, it could not practicably be carried out without using that information or those biospecimens in an identifiable format.
• No adverse effect on rights and welfare. The waiver or alteration will not adversely affect the rights and welfare of the subjects.
• Debriefing where appropriate. Whenever appropriate, subjects or their legally authorized representatives will be provided with additional pertinent information after participation.

All five criteria must be met and documented; a study that fails even one — most commonly criterion (i), because the research is more than minimal risk, or criterion (ii), because prospective consent is in fact practicable — cannot rely on this pathway.

Why retrospective and secondary-data studies rely on this waiver

In a retrospective chart review or a secondary analysis of an existing registry or claims database, the events being studied (a treatment, a complication, an outcome) already happened before the research began. Because nothing about the subject’s past care or exposure can change based on whether they consent now, and because these studies frequently require complete, unbiased cohorts rather than a self-selected subset of subjects who can be located and agree to participate, investigators routinely request a 46.116(f) waiver rather than attempting prospective consent from every individual in the dataset. The IRB’s job is to confirm, on the specific facts of that study, that seeking consent really would be impracticable (not simply inconvenient) and that using identifiable records is genuinely necessary to link visits, outcomes, or claims across time.

Where the records involved are subject to HIPAA, this Common Rule waiver is legally separate from — and typically obtained alongside — a HIPAA waiver of authorization under 45 CFR 164.512(i), which has its own, differently worded criteria. See HIPAA and Retrospective Research for how the two waiver analyses relate.

How this differs from documentation waivers under 46.117(c)

A 46.116(f) waiver of the consent process itself is a distinct provision from a waiver of the signed-consent-form requirement under 46.117(c), which applies to studies where consent is still obtained — just not necessarily documented with a signature, for example because the signed form would be the only record linking the subject to the research, or because the study is minimal risk and involves no procedures that would normally require written consent outside a research context. Confusing the two is a common documentation error: a study that has a full 46.116(f) waiver does not separately need a 46.117(c) form waiver, because there is no consent process being documented in the first place.

How this differs from Exception From Informed Consent (EFIC)

A full waiver of consent under 46.116(f) is often confused with Exception From Informed Consent (EFIC), but the two are separate regulatory pathways built for different situations:

• Scope of research. The 46.116(f) waiver is a general-purpose mechanism available across Common Rule research broadly, most often used for minimal-risk retrospective or secondary-data studies. EFIC, codified at 21 CFR 50.24 (with a related Common Rule counterpart at 45 CFR 46.101(i)), applies narrowly to prospective, FDA-regulated clinical investigations of a drug, biologic, or device in a life-threatening emergency.
• Risk level. 46.116(f) requires the research be no more than minimal risk. EFIC exists precisely because the research is more than minimal risk — it is an interventional emergency study — which is exactly why 46.116(f) is unavailable and a separate, far more demanding pathway with additional safeguards (community consultation, public disclosure, an independent data monitoring committee) was created instead.
• Timing. 46.116(f) is typically used where the subject’s exposure or outcome already happened (retrospective) or where records are being used for research purposes distinct from real-time treatment decisions. EFIC applies to subjects being enrolled and treated in real time, during a narrow emergency window, where no legally authorized representative can be reached before the intervention must occur.

In short: if a study is retrospective, minimal risk, and the question is whether existing records can be used without going back to each patient, 46.116(f) is the relevant provision. If a study is a live emergency intervention trial where a critically ill subject cannot consent and no LAR is reachable in time, EFIC is the relevant provision — and the two tests should never be treated as interchangeable or as alternative routes to the same finding.

Documentation IRBs typically require

Because 46.116(f) requires the IRB to make and document specific findings, investigators requesting this waiver typically need to address, in the protocol or waiver request: why the research is minimal risk; why obtaining consent (from the specific population involved) is genuinely not practicable rather than merely burdensome; why identifiable rather than de-identified data is necessary for the analysis; how privacy and confidentiality of the records will be protected; and whether any debriefing or post hoc disclosure is appropriate. IRBs generally will not accept cost or investigator convenience alone as a basis for impracticability.