Should a Protocol Amendment be Submitted in Advance of Consent Form Changes?

Question:

Should a Protocol Amendment be submitted in advance of Consent Form changes?

Response:

When compiling a protocol amendment, consent form revisions may also be required to ensure consistency between the approved research activities and what is presented to research participants throughout the consent process, pursuant to 21 CFR 50.25(a). From a process perspective, protocol amendments typically prompt consent form revisions, meaning that the updated protocol may be available for review first. But does that mean it should be submitted for IRB review ahead of the consent form documents? Generally speaking, the answer is no, unless appropriate justification for the delayed submission of the revised consent form is provided for consideration along with a way to notify both existing and new subjects of the changes in the interim.

Submitting a protocol amendment either in advance of, or independent of the associated consent form changes may result in a delay in the review process. The regulations specify that the consent form must present a clear and accurate representation of the research purpose, associated risks and benefits, and what is expected from participants to consent to take part in the research (21 CFR 50.25(a).). Thus, the IRB would expect the consent form changes to accompany the protocol amendment.

Importantly, ICH GCP also emphasizes the importance of prompt consent form updates, noting that “the written informed consent form and any other written information to be provided to subjects should be revised whenever important new information becomes available that may be relevant to the subject’s consent,” (ICH GCP E6 R2 Section 4.8.2). The IRB interprets this guidance to emphasize the importance of agreement between approved research activities and subject notification. In other words, if the protocol amendment alters any of information provided in the consent form, from what was originally approved, the IRB cannot approve these changes until the consent form accurately reflects these updates.