The Elements of Informed Consent and Key Information

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

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

Why this matters

Informed consent is where respect for persons becomes a conversation with a real person. If you know the required elements, you can tell when a consent form is missing something and explain the study without reading the form aloud.

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.

The basic rule and the conditions

Before involving a human subject in research, an investigator must obtain the legally effective informed consent of the subject or the subject's legally authorized representative (45 CFR 46.116(a)(1); 21 CFR 50.20).

Conditions on how consent is sought:

• Only under circumstances that give sufficient opportunity to discuss and consider participation and minimize the possibility of coercion or undue influence.
• With information in language understandable to the person.
• With the information a reasonable person would want in order to decide, and an opportunity to discuss it.

Key information

In the United States, under the 2018 Common Rule, informed consent must begin with a concise and focused presentation of the key information most likely to help a person understand why they might or might not want to participate. It must be organized to facilitate comprehension. The consent as a whole must not merely list isolated facts (46.116(a)(5)(i), (ii)).

The key information requirement is a 2018 Requirements feature, so it does not apply to studies still under the pre-2018 Common Rule. FDA's rule does not contain it: the text of 21 CFR 50.25 current on October 23, 2026 has no key information requirement. FDA and OHRP jointly issued a nonbinding draft guidance, "Key Information and Facilitating Understanding in Informed Consent," in March 2024. Ask your regulatory office what applies to your study.

No giving up legal rights

No consent may include exculpatory language through which the subject waives or appears to waive legal rights, or releases the investigator, sponsor, institution or agents from liability for negligence (46.116(a)(6); 21 CFR 50.20; ICH E6(R3) 2.8.4). If you see such a sentence in a draft, flag it to the PI.

The required elements

Common Rule basic elements (46.116(b)):

1. a statement that the study is research, its purposes, expected duration, procedures, and which procedures are experimental
2. foreseeable risks or discomforts
3. benefits
4. alternatives
5. the extent of confidentiality
6. for more than minimal risk, an explanation of compensation and of treatment for injury
7. whom to contact
8. a statement that participation is voluntary, that refusal involves no penalty, and that the person may discontinue
9. a statement about future use of identifiers or biospecimens (removed and possibly used, or not used)

Additional elements, when appropriate (46.116(c)): unforeseeable risks (including to an embryo or fetus), termination by the investigator, additional costs, consequences of withdrawal, significant new findings, approximate number of subjects, commercial profit from biospecimens, disclosure of clinically relevant results, and whole genome sequencing.

FDA (21 CFR 50.25): similar basic elements, including that FDA may inspect records. Additional elements include significant new findings and the approximate number of subjects. Applicable clinical trials must include the ClinicalTrials.gov statement (50.25(c)).

ICH E6(R3) (2.8.10): a longer list that also includes the statement when there is no intended clinical benefit, data handling, direct access to source records, circumstances of termination and results availability.

You do not need to memorize the lists. Know that they exist, overlap, and come together in your study's IRB-approved form.

Where to look for help

FDA's final guidance, "Informed Consent Guidance for IRBs, Clinical Investigators, and Sponsors" (August 2023), replaces FDA's 1998 "A Guide to Informed Consent." Only its existence, date and scope were checked for this course, so treat it as a pointer to read.

In practice

A coordinator reviews a draft consent form before it goes to the IRB. It opens with two pages of background. She asks the PI whether the key information could come first. She also notices that the draft says nothing about whom to call for a research injury question, and the risk section is missing a procedure the protocol includes. She flags all three in writing; the IRB makes the final call on the form.

What this looks like when it goes wrong

A site uses a form that says participants "give up any right to compensation for injury." Nobody notices, because the form has been used before. A participant who has a reaction asks about it, and the staff member is not sure what the form means.

The exculpatory sentence should never have been in the consent, and the staff member could not explain the form. Consent is only as good as the document and the person standing behind it.

Key takeaways

• Before involving a person in research, obtain legally effective informed consent from the person or the legally authorized representative.
• Consent is sought in circumstances that allow time to consider and that minimize coercion or undue influence, in understandable language.
• The 2018 Common Rule requires consent to begin with key information. FDA's current rule has no such requirement, and the joint FDA and OHRP guidance on it is a nonbinding draft.
• No consent may contain exculpatory language waiving legal rights or releasing parties from liability for negligence.
• The Common Rule, FDA and ICH E6(R3) each list required consent content, and the lists overlap.
• FDA's August 2023 final consent guidance exists as a resource. Ask your regulatory office what applies to your study.