Informed Consent Forms: common issues

The most important part of my job is protecting the rights, safety, and welfare of study subjects, and the key document for this activity is the Informed Consent Form (ICF). The ICF is the very first document I touch at each interim monitoring visit and the document I spend the most time composing during study start up. Here are some frequent ICF issues I've experienced- both writing/editing and monitoring- and how I avoid them:

1. Overly Technical Language ICFs should be written at an 8th-grade reading level or lower, but many IRB-approved ICFs are not written this way. Participants need to understand the study- not decode it. Consider whether a graph or a table might be a better way to represent some parts of the consent document like visit schedule, randomization, etc. There is a readability assessment in WORD you can use- under the HOME screen find the EDITOR then select INSIGHTS/ DOCUMENT STATS.

2. Missing Required Elements Every ICF must include specific components: purpose, procedures, risks, benefits, alternatives, confidentiality, etc. Omitting any of these- even unintentionally- can result in extending the start-up timeline to edit the ICF. I suggest creating a checklist based on ICH_E6(R3)_Step4_FinalGuideline_2025_0106.pdf section 2.8.10 for the study template and all final site-specific ICFs to ensure all the required elements are captured ahead of submission

3. Inconsistent or Conflicting Information Discrepancies between the protocol, ICF, and recruitment materials will cause confusion AND delays. Double-check that the schedule of events, risks, and procedures match across all documents, especially following protocol revisions.

4. Inadequate Risk Disclosure Glossing over known risks or failing to update the ICF when new information arises can endanger participants and damage trust. During the study, if you update the risk profile of the device, the ICF must be updated as well.

5. Incorrect Versioning or Lack of Tracking Version control is critical- at EVERY level. I've seen a few situations that really left an impression:

Sponsor: Everyone who touches the template ICF during the study must use track changes. Seriously- make this a hard rule. If someone forgets, you can use Word’s “Compare Documents” feature to identify what was changed… and then send the person who skipped tracking to ICF jail. (Just kidding—but not really.)

Site: In one situation, a site failed to incorporate all the redline changes from the template after an amendment. If the site doesn’t send the final ICF for Sponsor review before submitting to the IRB, it’s an absolute must to review the site-specific ICF post-approval to confirm all required changes were included.

Site: The issue I see most often during the course of a study is version control failed and a subject was consented on a previous version of the consent. What do I do when I see this?

First, I review the changes between the versions with the SC, this gives us an indication of how pressing the need is to re-consent the subject on the current version (i.e. does it need to happen NOW, or can it happen at their next visit)

Second, we talk about it- what happened and why. I make sure there are no immediate process issues we should address.

Third, generate a CAPA. The CA is always re-consent the subject, the PA will vary depending on the root cause. Generally, this will be some variation of making sure to pull the most recent version from their ICF database and not using a locally-saved ICF.

Four, enter the Protocol Deviation, make sure they capture all the pertinent information in the narrative section, including the CAPA

IRB: In another situation the central IRB received a correctly redlined ICF and reverted a redline. Luckily, I was reviewing the site-specific ICF post-approval to confirm all required changes were included and found the change wasn't included. After quite a few emails (read: time) I found the IRB had reverted the change. BTW, the central IRB was entirely unhelpful when I brought this to their attention. I saved the emails for my record, but they refused to generate a CAPA and instead promised to try to not do it again. Sigh.

At the SIV: Have a version control discussion with the Study Coordinator at the SIV or the first IMV. Ask them to walk you through their process. For example, if regulatory uploads the approved ICF to a portal, make sure the SC’s process is to always pull the most current version directly from that source- not from saved email attachments or desktop folders.

Amendment: Always use what I refer to as 'positive control' of protocol amendments. What this means is that a site is not activated on an amendment until they receive an activation letter for the amendment from me (as the CTM)- not when they send the final document, not when the IRB approves the amendment. I make this clear when I send the amendment notification email. The activation letter lists everyone that has completed the amendment requirements (typically training for personnel, signed Protocol Signature page for the PI, and IRB approval) and the current study/site staff that have not completed their requirements.

Amendment Activation Letter.docx

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6. Lack of documentation in the Consent Process Even with a solid ICF, problems arise if the consenting process is rushed or delegated to unqualified staff. Make sure the sites are set up to document the consenting process with enough detail to support the subject was given time to review the ICF, had their questions answered, and were given a copy of the signed ICF. If study procedures take place on the same day the ICF was signed, make sure the time of signature is recorded to demonstrate the ICF was signed prior to those procedures. Make sure the staff obtaining consent (both in the consenting documentation and consent signature) are delegated to obtain consent.

7. Administrative errors In my experience ICF errors with pagination, header/footer issues, and formatting consistently occur. Taking a minute to review the full, final ICF prior to submission can save time during or at the end of the study.

8. Signatures / LAR The most common signature error I see during ICF monitoring is a missed date or time (if required) next to signatures. I try to hit this point during training and explain WHY we collect this information (to demonstrate the ICF was signed prior to any study procedures).

Legally Authorized Representative (LAR): When I was managing/monitoring an acute care study it allowed for the use of an LAR signature on the ICF with the understanding the subject would sign the ICF after they recovered enough for Informed Consent to be obtained. However, the subject should sign a separate (not the same consent the LAR previously signed), current consent. This ensures the subject has the most up-to-date information for their consent and decision process AND protects them from being coerced into providing consent by seeing their LARs 'permission' in writing. The subject consent process should also have separate documentation.

Note on LAR/Witness: LARs should NOT be used in cases where the subject is cognitively capable but cannot write for any reason, cannot read, etc. These would be situations where a WTNESS, not an LAR, should be utilized, and this should be made clear in the consenting documentation.

Preventing ICF issues starts with proactive planning—developing a readable, comprehensive, and harmonized document, and ensuring sites are trained on proper consent procedures. Addressing these common issues early can save time, protect subjects, and keep your trial on track.