What’s New in E6 R3? Investigator Responsibilities Part 2 – Informed Consent

In this series of blog posts, we’ve been looking at the changes in Revision 3 of the ICH Good Clinical Practice E6 guidance.  Today, we look at the Informed Consent section where – no surprise – the pandemic gets name-checked.

First, some general changes:

• In this section as in the rest of the updated guidance, the term “subject” has been replaced by “participant.”
• The R2 term “laws and regulations” has been replaced by “applicable regulatory requirements,” which has been deployed throughout to indicate that delegation of informed consent responsibilities is subject to local laws
• The R2 term “designated by the investigator” has been replaced by “delegated by the investigator” in reference to delegation of informed consent duties.
• The R2 term “payment” has been replaced by “compensation”
• Subject “responsibilities” are now referred to as participant “obligations,” emphasizing the participant’s active commitment and importance

Next, substantive changes:

Starting Point.  R3 clarifies that IRB/IEC written approval must be obtained “prior to consenting and enrolling participants,” replacing the more ambiguous wording “the beginning of the trial.”

Language. Where R2 stated that informed consent language should be “non-technical” and “understandable,” R3 describes desired language as “clear and concise as possible” and “simple,”  with an overall goal of ensuring participants’ understanding of the trial.  Per R3, informed consents should also “”avoid unnecessary volume and complexity,” music to the ears of those of us who regularly review long, repetitive ICF models.

Alternative methods of consent.  R3 adds a step permitting “varied approaches (e.g., text, images, videos, and other interactive methods” for informed consent, as well as remote consent “where appropriate.”  Criteria for appropriateness are not specified.

Ample time. The requirement to give participants “ample time” to review the informed consent has been qualified with “unless justified (e.g., in an emergency situation).”

Signatures.  In addition to signatures by the subject/legal representative and person conducting informed consent discussion, R3 notes that “where appropriate” the form may be signed by an impartial witness, to bring this section in line with the requirement for an impartial witnesses in cases where both the participant and their legal representative are unable to read. A new statement notes that signatures may be handwritten or electronic.

Minors and Other Participants Requiring a Legal Representative.  R3 suggests that a re-consent process should be considered if a minor participant reaches the age of legal consent during the trial.  R3 also distinguishes between minor participants who should receive “age-appropriate assent information” and participants who require a legal representative (a group that includes minors), who should receive information “to the extent compatible with the participant’s understanding.”

Required elements.  The following new required elements have been added:

• A summary of the experimental aspects of the trial
• Risks  and inconveniences to the participant’s partner, when applicable
• Process by which the participant’s data will be handled, including in the event of withdrawal of participation
• A statement that the trial may be registered on “publicly accessible and recognized databases”
• A statement that the trial results and treatment assignment, if appropriate, will be made available to participants if desired.  Note that this step does not specify that this information will be communicated post-unblinding.

Public health emergencies.  R3 notes that in exceptional circumstances, alternative methods and technologies for informed consent may be used per local IRB/IEC guidance and regulatory requirements.