Common Audit Findings - Informed Consent

Hi, Elizabeth here, and welcome!

In this post I will begin discussing common audit findings, and one of the first ones I think of involves informed consent.  This is a big one.  By the end of this post, you will learn some of the common audit findings regarding consent and some tips that will assist you when monitoring.

So, let us start with the common issue regarding subjects not consented with the correct version of the Informed Consent Form (ICF).  Yikes, right!!  Unfortunately, this happens a lot.

As you may know, when a subject is consented, the most current IRB approved version of the consent form should be used, and we see issues with this a lot as monitors.  You may see the newest IRB approval filed in the Regulatory Binder; however, the new subject did not sign this version.  It ends up the subject signed a previous version.  

This is one of the reasons why during my first visit to a site, I like to start with the Regulatory Binder.  That way, I am aware of all the IRB approvals and versions of the consent form prior to subject review.  While completing my Reg Binder review, I document the information on an ICF tracker in order to maintain an organized list of all versions.

I use this to track which version is the most current when a new subject comes in to sign consent, as well as, keeping track of the existing/active subjects that also need to sign the updated version.  Remember, when there is a new version of the ICF, all new and active subjects are to sign the revised version.

This is why a tracker is so important, as another common audit finding is regarding a lack of reconsent or providing new information when required by the IRB.  When an ICF is updated, it is important that a site confirms if it can wait until the active subject’s next study visit or if it is something that they must notify the subject about immediately.  For example, I was on a study where there was a new safety issue, which resulted in a revised consent form.  The update was something that could affect the subjects' willingness to continue their participation in the study.

The ICF template had to be updated with the new safety information, approved by the sponsor, and then approved by the IRB.  So, the subjects being informed of this new safety issue, could not wait until that time.  The sites had to contact all the subjects immediately with the new safety information and then document this contact in the source.

Then, when the site received the IRB approval and attached updated ICF, the site had to reconsent those subjects also.  So again, when there is an updated consent form, it is especially important that the site confirms if this an update that the subjects need to be contacted about immediately prior to resigning the consent form or if it is something that can wait until their next study visit.  Sometimes there may be an updated address, for example, that results in a revision to the consent form and typically can wait until the subject’s next visit.

As monitors, we need to track this as well.  We must ensure that all new subjects have signed the most current IRB approved version of the ICF at the time they came in, and that all active subjects are reconsented with the revised version also.

So, picture this….I inherited a site, which was a high-enrolling site.  There was going to be a study-wide interim data analysis and the site was also chosen for a QA audit as they were high-enrollers.  Wow, talk about stressful!!  So, in addition to catching up on data review for the upcoming data analysis, I also had to prepare them for the audit.  It also happened to be a site that not only had multiple versions of the consent form, but they were in two different languages!!  Lots to keep up with.

I had to make sure that they had every single version available in English and every single version available in Spanish.  My tracker was very full.  It definitely came in handy when confirming if each subject signed the most current version at the time of consent, and that all active subjects were reconsented appropriately as well.  As I inherited the site, I also used the tracker to ensure that all applicable versions of the ICF were present for each and every subject.   

Another common issue is inadequate documentation of the consent process.  The ICF is not just a form or document, it is a process.  After a subject signs and dates the ICF, the consenter is going to sign and date the ICF, and then the consent process should also be documented in the source.  For example, did the subject have sufficient time to review the consent?  Was consent obtained prior to any study related procedures being performed?  Did the subject receive a copy?  These are some of the things we should be looking for in that consent process.  Some sites, in addition to documenting the consent process, may also have Standard Operating Procedures (SOPs) that indicate their site's consent process procedures.  This is something that we review at the Pre-Study Visit and Initiation Visit as well.

Remember in clinical research, when something is not documented it didn't happen.  It is so important that we see this process documented in the source to ensure it was performed appropriately and per all regulations.  This applies when initially consenting a subject for study participation, as well as, when a subject is reconsented. 

So, in this example, when taking over the site, there were multiple versions of the ICF for each subject, and after review of the individual ICFs, I wanted to see the consent process documented in the source (for each one).  I would look at the date signed, then I would go to the source under that visit date and look for documentation of the consent process.

Many times, I would see that initial consent process documented, but not when the subjects were reconsented.  There was no documentation in the source that it even happened.  Sites must be made aware of the importance that when a subject signs an ICF, and even an updated ICF, that the process is documented in the source, and we as monitors must verify that.

Like I mentioned above, we need to confirm that no study procedures were performed prior to obtaining consent.  Consent must be obtained first, prior to any study-related procedures being performed. This includes when a patient has to wash-out of a medication prior to screening.  I have seen this before when reviewing medical records, where a subject stops a disallowed medication.....I am like, wait a minute, this date is before the subject was consented for the trial.  I immediately follow-up with the site in order to confirm if the subject was asked to stop taking this prior to screening and consenting…..and I am thinking inside my head, if so this is wrong on so many levels.  Some sites may report no, that the subject stopped the medication due to insurance purposes, and then in that case, I would explain that this needs to be clearly documented in the source.  If you find out otherwise, then definitely escalate this to your study team.   

There are times that the ICF or the consent process will also include the time of consent, which I like because that way I can really ensure that none of the study procedures were performed prior to the subject signing consent.  So, if it did include the time that consent was obtained, then I would jot that in my notes as well.  This helps as I am reviewing the source for the screening visit.  When I would see a time that a procedure was performed, like labs, for example, I would look at the time of consent in order to verify that labs were not collected prior to signing consent.  I would do this throughout my review of the screening visit source; continuing to compare those times to double-check and verify that consent happened first.

We also want to ensure that the person obtaining consent, the consenter, has been delegated to do so by the PI.  We can confirm this by looking at the Delegation of Authority Log that is filed in the Regulatory Binder.  The acronyms or the title of the log will depend on the company that you work for.  Sometimes it may be called a Delegation of Authority Log, Site Delegation of Responsibility Log, or Site Signature Log.  You get the gist 😉

Review the log, look for the name of the consenter, and verify that this person was delegated appropriately by the PI to obtain consent.  You also want to be familiar if there are any local laws regarding this as well.  For example, in Pennsylvania, I remember where a supreme court had ruled that a physician may not delegate to others his or her obligation to provide sufficient information in order to obtain informed consent.  Another example is California with the California Bill of Rights that must be signed in addition.  Be familiar with the state local laws as well. 

Another common finding is a missing HIPAA authorization, which is huge!  If we do not see a signed consent AND a signed HIPAA, we cannot review that subject.  It is so important that both documents are present, signed, and reviewed by the CRA prior to any source review.  Remember this also when inheriting a site.  Even though the previous CRA may document that they have reviewed the ICFs and HIPAA for a particular patient, I like to verify it for myself as the consent and HIPAA are so important.  I want to confirm that the ICF and HIPAA were signed appropriately and filed with the source.

I have another example…I inherited a site that utilized a central IRB, and in my experience most of the central IRBs would incorporate the HIPPA with the consent.  So, there may be 19 pages of the consent form and maybe on page 17, they sign/date consent to participate in the study, and then maybe on page 19 is where they sign/date the HIPAA portion of the document.  When I began my review of the ICF/HIPAA for one of the subjects, I noticed that the HIPPA page was not signed and dated, and I almost fell out of my chair because that subject should not have been reviewed by the previous monitor.

I immediately closed the chart, escalated the issue, and documented the issue in my trip report.  I also had to re-educate the site staff, the site had to notify the IRB of the issue, and then of course the subject had to sign/date the HIPAA as a late entry before I could review anything.

That was definitely a surprise to come across my first time taking over the site.  Also, to boot, the site had to update all of their consent forms across all studies as they had an address change.  During my review, I observed where a subject signed the revised consent form with the address change; however, when they signed the updated consent, it was for a completely different study!!  I almost fell out of my chair again!  I should have just stayed on the floor LOL!!  So, this was another issue we had to resolve….and again, as I mentioned, I definitely recommend, even if you are taking over a site and it may be documented that the previous CRA reviewed the ICFs/HIPAAs already, I highly recommend verifying it for yourself.

This is not an all-inclusive list of consent issues by any means, I could go on and on regarding issues with the ICF, including issues with signatures/dates, initials by the subjects that are missing, dates that are incomplete, dates that do not match between the subject and the consenter, or even a coordinator that dated for a subject.  Oh, my goodness, I could not get over that one!!!  So, there are definitely a variety of issues that I have come across in my experience, and it would take so much longer than one post to go through it all.  My course will go into detail regarding review of the consent form and everything that we need to verify as monitors during that review. Very informative 😊

Thank you so much for being here!!  For my next post, I am going to continue with the discussion of common audit findings, and you will have to wait in suspense which one I am going to choose LOL!! 😊

Thank you again, I pray you guys are safe out there.  Let's work together to flatten the curve and stop the spread of COVID-19.

Again, please stay safe!

XO,

Beth