Principal Investigator oversight, or the lack thereof...

In a clinical trial the sponsor takes overall responsibility for the (quality) management of the trial - even if they delegate some / all their responsibilities to a service provider like a contract research organization (CRO). The same applies at site level. During the conduct of the trial, you have a lead investigator (usually a medical doctor or scientist), that in some countries are referred to as the principal investigator (PI) that takes overall responsibility for the medical care of the participants and conduct of the trial at site even if the PI delegates certain/all tasks to the team at site. Our good clinical practice guidelines (GCP) are clear – nor the sponsor nor the PI can delegate their “overall responsibility” – that remains their responsibility respectively. To do that they need to ensure they maintain oversight of their trial.

SA GCP goes as far as to say, “it is unacceptable to have an absentee PI”. "Why would you have an absent PI?" you may ask. Well, there are many reasons, and it is not an uncommon phenomenon when it comes to clinical trials in practice. For one, a research site might be experienced in a certain indication. When you take on a trial that requires other expertise knowledge you might need to appoint a PI that has access to this population and expertise to treat, while your team has the expertise in running the trial. This PI might not be based at your research site but at their private practice. Or your PI at your institution is also a professor in academia, linked to a tertiary institution and due to them wearing multiple hats cannot always be hands-on at site. Or maybe you do not have experienced investigators that can step up to take on the role of PI and you as the experienced investigator needs to be the PI on multiple studies.

In all these examples you will often have the scenario where the sub-investigator (your doctors reporting into the PI) and / or the study coordinator is the hands-on team at site and the PI only has study oversight. Having said that, it is critically important to show the PI’s involvement and active oversight in participant care and study conduct from start to end as this remains their responsibility as clearly stated and expected by GCP. And not showcasing that will be a major finding.

 So how do you “show” PI oversight in a clinical trial?

 Here are some practical tips to ensure (documented) PI oversight:

1.    The PI must attend the site initiation visit so that training on the protocol is recorded. As a bare minimum the (experienced) PI must document that they self-studied the protocol and investigator brochure before study start.

2.    The site and CRA needs to always keep PI in all communications.

3.    If there is any event regarding a participant, it is best practice for the nurse or sub-investigator to bring this to the attention of the PI. Discuss this with the PI. Document this discussion in an email with the PI and request a response and file this communication in your participant source file.  

4.    Keep the PI up to date with any suggested protocol or informed consent amendments or changes in processes on the study as well as updated training.

5.    The PI must sign the accumulative protocol deviation log for the study on a regular basis (at least every second week), especially if there are major deviations reported. If the PI is out of town the site can email the logs to the PI and the PI can acknowledge them via encrypted email - file that in the site file - or if you have a 21 CFR part 11 compliant electronic signature system - even better.

6.    The PI must review all prepared study progress reports for submission to authorities and sign them off.

7.    When the PI is out of town, they can opt to remotely delegate the staff member by verifying their training via email and assigning tasks via email - remember to file that email with the delegation log, showcasing the date of delegation. The PI needs to remember to then go to site to delegate in wet ink in a reasonable time.

8.    All safety letters (SAE / SUSAR) must go through the PI – to sign and file.

9.    The CRA follow up letters must reach the PI. The PI needs to make a point to read and reply to the follow up letters so that the site can file PI response to the letter in the site file to show PI acknowledgment.

10. The PI must make time to at least attend the exit meeting of the CRA visit.  If they cannot do that in person on that day - schedule an alternative date and time to meet at site / off site. If that is not possible schedule to meet virtually and request the CRA to document this visit in their report.

11. Lastly – if you are an “external” PI or “off-site” PI - schedule monthly meetings (face to face or virtual) with your team and discuss: the progress of the trial, recruitment challenges, enrolment targets, new adverse events, trends in protocol deviations, corrective actions, preventative actions (CAPA)l IP management etc. and minute these meetings and file them per study.

 We can agree to disagree on our opinions about the involvement of the PI in a clinical trial- the fact remains, it is not always possible and practical for the principal investigator to be “hands-on” and on site. However, there is no excuse for an absent PI who does not showcase oversight. At the end, the PI takes ultimate responsibility for the conduct of the trial. That is the one task they cannot delegate. By implementing these 11 steps I believe that you will have proven your continuous effort as the PI in safety oversight in the conduct of your trial and the oversight in medical care that your participants deserve.  

K C