Informed consent is frequently described as if it were a single event: a form, a signature, a checkbox in a screening log. It is not. Federal regulation treats it as a process with distinct stages, each carrying its own documentation and timing requirements. This guide walks through that process step by step, from confirming eligibility to the ongoing re-consent obligations that can persist for the life of a trial.
This page focuses on the procedural sequence — what happens, in what order, and what has to be documented at each step. For the underlying regulatory requirements themselves (voluntariness, disclosure, comprehension, capacity, special-population protections, and the substantive waiver criteria), see Informed Consent in Research: What It Requires and How It Works. For a section-by-section annotated example of the form itself, see Informed Consent Form: A Worked Example With Annotations. For the specific timing rules around when consent must be obtained and what triggers re-consent, see When Should Informed Consent Be Obtained? — this page summarizes those triggers as one step in the sequence below but defers to that guide for full detail.
The consent process, step by step
Step 1: Confirm eligibility before the consent conversation begins
Consent is sought from a prospective participant who has already been identified, through a screening log or referral, as plausibly meeting the protocol’s eligibility criteria. Initiating a full consent discussion with someone who clearly will not qualify wastes the participant’s time and can create the appearance that enrollment was predetermined. Some preliminary, protocol-specified screening procedures may themselves require a separate, narrower consent (a “pre-screening” or “screening consent”) before any protected health information is reviewed for eligibility purposes — check the protocol and IRB/REC-approved consent documents for whether a two-stage consent structure applies.
Step 2: Provide the approved consent document and adequate time to consider it
The person obtaining consent provides the current IRB/REC-approved version of the informed consent form (ICF) and, where the protocol calls for it, any separate information sheet. Under 45 CFR 46.116(a)(1), consent may be sought only under circumstances providing the prospective participant “sufficient opportunity to discuss and consider whether or not to participate” — in practice, this usually means giving the participant the document in advance rather than presenting it for signature in the same sitting as the first read-through, particularly for higher-risk studies. ICH E6(R2) Section 4.8 places the same expectation on investigators: adequate time and opportunity to inquire about study details before deciding.
Step 3: Conduct the consent conversation
This is the substantive core of the process — the conversation is the consent; the form only documents that it happened. A well-run consent discussion:
- Takes place in a private setting, without the presence of anyone (a treating clinician, a family member the participant may feel pressure from) who could compromise voluntariness.
- Covers the required disclosure elements in language the participant can understand — purpose, procedures, duration, foreseeable risks and discomforts, expected benefits, alternatives to participating, and confidentiality protections.
- Includes a comprehension check, not just a disclosure. A “teach-back” approach — asking the participant to explain key points (such as what happens if they’re injured, or that participation is voluntary) in their own words — is widely used to confirm understanding rather than assuming a signature implies it.
- Leaves real room for questions, and answers them before moving to signature.
- Explicitly confirms voluntariness and the participant’s understanding that declining involves no penalty or loss of benefits to which they are otherwise entitled.
- Uses a qualified interpreter, and a translated or short-form consent document, where the participant is not fluent in the language the standard ICF is written in (see Step 5).
Where capacity to consent is uncertain — cognitive impairment, acute illness, minors — this step routes to a legally authorized representative (LAR) consent or a parental-permission-plus-child-assent structure instead of, or alongside, first-person consent. See Informed Consent vs. Assent for how that distinction works in practice.
Step 4: Document the discussion itself, separately from the signature
45 CFR 46.117 regulates documentation of consent separately from the consent process described in 46.116 — the signed form is not the only record that should exist. Good practice (and most institutional SOPs) call for a contemporaneous source note describing when and where the discussion occurred, who was present, how long it took, and confirmation that questions were answered and comprehension was checked. This source documentation is what an auditor or monitor relies on to verify the process actually happened as the form implies, and it’s part of what ICH E6(R2) Section 8 treats as an essential document supporting the trial’s conduct.
Step 5: Obtain and record signatures
The standard path is a full written consent document signed and dated (or time-stamped, for eConsent) by the participant or their LAR, and by the person who conducted the consent discussion. Two variant paths exist:
- Short-form consent (21 CFR 50.27(b)(2); a parallel mechanism exists under 45 CFR 46.117(b)(2)). Used when a participant cannot read the standard IRB-approved document — commonly a non-English speaker where no translated long-form version exists. The IRB approves a written summary of what will be said; the elements of consent are presented orally, with a witness to that oral presentation. The participant (or LAR) signs only the short form; the witness signs both the short form and a copy of the summary; the person obtaining consent signs a copy of the summary; the participant receives copies of both.
- eConsent. Electronic signature and, often, interactive comprehension checks embedded in the platform, governed by the same 46.116/46.117 substance plus FDA electronic-records expectations (21 CFR Part 11) where applicable. See eConsent (Electronic Informed Consent).
Step 6: Provide the participant a copy
The participant (or LAR) must receive a copy of the signed consent document — this is an explicit regulatory requirement, not a courtesy, under both 45 CFR 46.117(a) and 21 CFR 50.27(a). For short-form consent, the participant receives copies of both the short form and the signed summary.
Step 7: File the consent record among the trial’s essential documents
The signed ICF, the source note from Step 4, and (where applicable) the signed summary from a short-form consent all become part of the site’s regulatory/essential-document file — the record an inspector or monitor will check first when verifying that a specific participant’s enrollment was properly consented. Version control matters here: sites running a multi-year trial commonly have several ICF versions in circulation as amendments are approved, and the essential-document file needs to make clear which version each participant actually signed.
Step 8: Monitor for re-consent triggers throughout the trial
Consent obtained at enrollment does not exhaust the requirement. A participant needs to be re-consented — walked back through some or all of the process above, on a revised document — when new information emerges that a reasonable person would want in deciding whether to continue: a protocol amendment that changes the risk/benefit profile, newly identified significant safety information, or a substantive revision to the approved ICF. When Should Informed Consent Be Obtained? covers the timing rule and the specific triggers in full, including the narrow prospective-consent exception for emergency research under 21 CFR 50.24 / 45 CFR 46.101(i).
Documentation requirements: 45 CFR 46.116 vs. 46.117
These two provisions are frequently conflated but regulate different things:
- 45 CFR 46.116 sets the substantive requirements for the consent process itself — what must be disclosed, and under what conditions consent is validly obtained (voluntariness, opportunity to consider, understandable language, the required disclosure elements).
- 45 CFR 46.117 governs how that consent is documented — generally a signed and dated form, with the short-form and eConsent variants described in Step 5 above.
Because these are separate provisions, it’s possible for an IRB to waive the documentation requirement while the underlying consent process still has to occur, or — much more rarely, under a separate test — to waive elements of the process itself. Both are covered next.
When documentation of consent can be waived
Under 45 CFR 46.117(c) (parallel provision at 21 CFR 56.109(c) for FDA-regulated research), an IRB may waive the requirement for a signed consent form — not the consent process itself — in two circumstances:
- The signed form would be the only record linking the participant to the research, and the principal risk of the research is a breach of confidentiality from that link. In this case, each participant is asked whether they want documentation linking them to the research, and their wishes govern.
- The research presents no more than minimal risk of harm to participants and involves no procedures for which written consent is normally required outside of a research context.
This is a narrower, more commonly used waiver than a waiver of the consent process itself, which sits under a separate provision (46.116(f)) with its own four-part test: the research must be minimal risk, the waiver must not adversely affect participants’ rights and welfare, the research must not be practicable without the waiver, and participants must be provided pertinent information after participation where appropriate. Sites sometimes treat these as the same waiver — they are not, and an IRB approval letter should specify which one applies.
Frequently asked questions
Who is allowed to obtain informed consent?
Regulation does not require the person obtaining consent to be a physician or the principal investigator — it requires that person be qualified and appropriately delegated under the site’s protocol-specific delegation-of-authority log, and, in practice, trained on the specific protocol and consent document. Many sites delegate this to a clinical research coordinator.
Is verbal consent ever sufficient on its own?
Only within the short-form process described in Step 5, and even then a witness and a signed short form/summary are required — a purely verbal, undocumented consent does not satisfy 45 CFR 46.117 or 21 CFR 50.27 outside that specific structure, or where an IRB has separately waived documentation under 46.117(c).
How long should a consent conversation take?
Regulation sets no fixed minimum, but “sufficient opportunity to discuss and consider” (46.116(a)(1)) is the operative standard, and IRBs increasingly expect sites to document time spent as part of the source note in Step 4 — a consent visit rushed to fit a clinic schedule is a common audit finding.
Does every protocol amendment require re-consenting already-enrolled participants?
No — only amendments that change information a reasonable participant would want in deciding whether to continue, most commonly a change to the risk/benefit profile or new safety information. Purely administrative amendments typically do not trigger re-consent. See When Should Informed Consent Be Obtained? for the full trigger list.
