INFORMED CONSENT – 5 CRITICAL ELEMENTS TO MONITOR

Ensuring proper informed consent in clinical studies is a critical process, that protects the rights, safety, and welfare of human subjects involved. It will require even more attention under the new GDPR and with the globalization of clinical trials. Although most involved are aware of its relevance, yet there is hardly a process where I see the same issues over and over again during monitoring visits and audits. The annual GCP Inspectors Report indicates that ICF findings were 5th on the list in 2015. This post addresses the 5 most common findings as well as options for preventive measures:

Language

The purpose of the informed consent process is to inform the candidate study participant on what it means to participate in clinical research and the concerning study in particular: what are the risks and possible benefits, what are you supposed to do and not to do as a participant, and what it is you can expect with respect to your health. All of this should be done in language understandable to the subject (or authorized representative) and in as few pages as possible, to ensure that the candidate study participant can make an informed decision.

Yet, I often come across patient information letters containing complex medical and scientific texts, clumsily translated from an English master, and sometimes even in a language different from the subjects own. To simplify the information letter provided to candidate study participants, local (hospital) information brochures on the concerning medical procedure and/ or disease can be of great help, as well as asking team members to read and provide feedback on the information letter, and using the readability statistics tool in word. And last but not least, ensure to have the information letter and consent available in all applicable local languages.

Content

With the requirement to keep the information as understandable and lean as possible, it is easy to forget to address some of the required elements. What I often find missing, for example, is a reference to the (potential for) personal data being transferred to a country outside of the EU: Under the current EU data-protection regulations, and even more so the new GDPR, the definition of what is considered personal data is very broad and also concerns pseudo-anonymous health data, and one needs to be careful sending such data to third countries with different (typically less stringent) laws in that respect (also refer to my previous post on this topic). Third countries, by the way, include the US, and one should pay attention now that the Privacy Shield is at risk.

Of note in this respect is also, that even though an Ethics Committee has approved an Informed Consent with missing elements, this does not mean you are compliant with the EU data-protection regulations: ISO 14155-GCP clearly states that:

“If national or regional EC requirements are less strict than the requirements of this International Standard, the sponsor shall apply the requirements of this International Standard”, and the standard requires you comply with …”

Tools that can help to ensure your information letter and consent form contain all locally required elements are templates and checklists provided by the local Ethics Committees, as well as your own checklists that you build with time.

Study participant sign off

Good clinical practices are very clear with respect to the fact that the informed consent needs to be signed and dated by the subject him/ herself. ISO 14155 states that:

“… the informed consent shall … include personally dated signatures of the subject and the principal investigator or an authorized designee responsible for conducting the informed consent process”

Still, I find it happening over and over again that a consenting physician or study nurse dates the consent in an attempt to help the subject. Despite good intentions, this really is a ‘NO GO’. The sign off namely indicates that the subject was personally and timely involved, i.e. before the start of the study or data-collection, and therefore needs to be done by themselves. Besides emphasizing this during the site initiation, the most creative preventive measure I have seen so far is an embedded “stamp” on the consent page that says

“the patient needs to sign and date him/ herself”.

Children

Less than 1/3 of treatments are studied in children, which is a big issue for the applicability of medical products. One of the reasons is that research with minors is only allowed when it meets specific requirements, which includes the informed consent process. In general (the regulations differ per EU country) the informed consent needs to be signed and dated by both parents or their legal guardian when the child is below a certain age, and by both parents or their legal guardian and the child when (s)he is considered capable to understand the informed consent process until the age of 18.  When the child becomes an adult (typically 18) in the course of the study, in The Netherlands (s)he needs to (re)sign the (adult) consent. Requirements in The Netherlands are expected to be broaden in this respect per March 2017, such that re-consent is not required anymore and the transition age becomes 16 years conform the new GDPR.

With the need for more signatures, unfortunately the chances for mistakes multiply, and I have seen several partially signed informed consents. Also the re-signing when becoming an adult is something that is easily forgotten, so I am happy to see the broadening of the Dutch regulations in this respect. Nevertheless such mistakes are best prevented, and it is key to know the local requirements when running a clinical study with minors, to ensure adequate training of the site study team during the initiation in this respect, and to install alerts in your EDC system to warn you ahead of time when a subject becomes of age.

Version

Every-one involved in clinical studies is aware that the (latest) EC/ IRB approved version of the informed consent should be used. In spite of that, even the best study sites make the mistake to use an old or wrong version. Often because the consenting physician did not have the correct version available after an amendment, or because (s)he did not realize there were different languages available.

The only way to prevent this from happening is to ensure that all involved in informed consent process only have access to the latest, correct version, and that all are aware (by emphasizing this during the initiation) that multiple languages are available should this be expected.

Conclusion

With the above it certainly feels like I am stating the obvious, but apparently there is still room for improvement in the informed consent process. Too bad, since there are plenty of tools and options around to ensure that this key process in clinical studies is handled the right way, and prevention is much, much better than cure; Especially since corrections tend to lead to new mistakes.

Should a correction be necessary then, as a rule of thumb, follow good documentation practices and ensure that for transparency reasons any change, addition, or correction is dated, signed, and explained by the person doing so (could be the study participant!), and involve the concerning Ethics Committee in this process.

Please feel free to reach out in case you want to discuss any of the above or are looking for a monitor or auditor.