Re-consent, Representatives, Waivers and Emergency Research

Part of Human Subjects Protection for Clinical Research Staff: Informed Consent.

About 5 minutes. Free, in your language, no account needed.

Why this matters

Consent does not end at the first signature, and it is not always the participant's own signature. This lesson covers new information, representatives, waivers and emergency research. Waivers and emergency research are awareness topics: they are decisions for IRBs and investigators, not coordinators.

ICH E6(R3) sets the international baseline for the consent process and its content. The US rules (HHS 45 CFR 46 and FDA 21 CFR 50) are taught as the detailed worked example, and passages naming them are US law. Outside the United States, follow your national law and ethics committee requirements, which may add to or differ from what you read here.

New information and re-consent

Under ICH E6(R3) section 2.8.2, new information that may be relevant to a participant's willingness to continue is communicated in a timely manner, and the communication is documented. The information is also assessed to decide whether re-consent is needed. Revised materials show the new information clearly and need IRB/IEC approval before use.

The Common Rule and FDA both list significant new findings, to be provided to participants, as an additional consent element (46.116(c)(5); 50.25(b)(5)). IRBs keep statements of them in their records.

A good habit: if you learn something that could change a participant's decision, tell the PI at once. Do not decide re-consent questions yourself.

Legally authorized representatives

Under the Common Rule, a legally authorized representative (LAR) is an individual or a judicial or other body authorized under applicable law to consent on behalf of a prospective subject. If no law applies, it is a person recognized by institutional policy as acceptable for consent in the nonresearch context (46.102(i)). ICH E6(R3) says "legally acceptable representative" for the same idea.

ICH E6(R3) says that if a participant cannot consent, for example a minor or a person with severely impaired decision-making capacity, the representative consents. The participant is still informed in a manner that facilitates understanding and, if capable, signs or dates the consent or assent form (2.8.5, 2.8.13; Principle 2.1).

A good habit: before anyone signs as a representative, confirm with your regulatory office or IRB who qualifies. Do not guess.

Broad consent

In the United States, broad consent is a 2018 Common Rule feature with no FDA counterpart. It is an alternative to ordinary study consent that applies only to storage, maintenance and secondary research use of identifiable private information and identifiable biospecimens, and it has its own required elements. If a person was asked for broad consent and refused, an IRB cannot waive consent for that storage, maintenance or secondary use (46.116(a), (d), (f)(1)).

Waiver or alteration of consent

An IRB may waive or alter consent only if it finds and documents that the research involves no more than minimal risk, could not practicably be carried out without the waiver or alteration, and (if it uses identifiable data or specimens) could not practicably be carried out without them in identifiable form. It must also find that the subjects' rights and welfare will not be adversely affected and, whenever appropriate, that subjects will get additional information afterward (46.116(f)(3)).

FDA added a parallel minimal risk waiver or alteration in 2023 (21 CFR 50.22). The IRB decides. You never waive consent because something is "only minimal risk."

Emergency research: awareness only

FDA allows an exception from informed consent for certain emergency research (21 CFR 50.24). The IRB, with the concurrence of a licensed physician not otherwise participating, must find and document each of a list of criteria, including a life-threatening situation, consent not being feasible and a prospect of direct benefit. Additional protections include community consultation, public disclosure and an independent data monitoring committee. It must be performed under a separate IND or IDE.

Separately, 21 CFR 50.23 deems consent feasible unless the investigator and a physician not otherwise participating certify in writing a life-threatening situation, inability to obtain consent, insufficient time to reach a representative, and no alternative with equal or greater likelihood of saving life. Documentation goes to the IRB within five working days.

ICH E6(R3) also addresses emergencies. When prior consent is not possible, the representative's consent is requested if one is present. If not, enrollment needs measures described in the protocol with IRB/IEC approval, and the participant or representative is informed as soon as possible (2.8.8; Principle 2.4).

In practice

A site receives a safety letter describing a new risk. The coordinator calls the PI right away. The PI decides whether re-consent is needed and sends revised materials to the IRB. Once the IRB approves them, the coordinator tells enrolled participants, answers questions and documents the conversation.

What this looks like when it goes wrong

A participant's adult son, who often handles his father's paperwork, signs the consent form because the father is confused during a visit. Nobody checks whether the son qualifies as a legally authorized representative under applicable law and institutional policy.

The form is signed, but the signature may not be valid consent. Being a relative, or being in the room, does not by itself make someone a representative.

Key takeaways