It is now a requirement under ICH GCP E6 (R2) addendum for the Principal Investigator (PI) to demonstrate their oversight of a clinical trial. Sites need to be able to provide evidence that the PI is actively involved in the conduct of the trial and is assuming the required responsibilities. As they are considered personally responsible for conducting and supervising the conduct of all trial activities the PI should have a plan for the supervision of all staff working on the trial. The delegation log is not a paper exercise, the PI needs to be able to support their actions if questioned.
There has been considerable thought around the format that will be required in the case of an inspection.
Centres should hold regular meetings of the research team. These should be minuted, documenting all those present. Most sites run multiple trials and so confidentiality must be a consideration. Study names could be used but sites must be wary of making restricted information available to outside parties. However, the minutes could contain study status, SAEs and AEs discussed, safety issues and Protocol violations and deviations – these are linked to particular members of the team indicating inappropriate delegation or that re-training is required. If necessary, agreed identifiers could be attributed to each trial so that the Sponsor can evaluate the amount of discussion for their study.
The Sponsor can be involved with monitoring PI oversight. The CRA has a close working relationship with the site staff and can flag concerns. During SDV they can identify how often the PI is present at patient visits, and how regularly the visit is completed by a sub-investigator. How often the PI is present at informed consent can be verified by the signature on the form. The CRA is also able to record the availability of the PI at a monitoring visits in their follow up letter and all issues discussed. This should also be used as an opportunity for the Sponsor to assess the PIs knowledge of the Protocol, the patients enrolled and how the trial is progressing at site. Concerns can then be addressed at an early stage.
Together with the site staff the CRA could identify the amount of data queries linked to each staff member. The PI would then need to document the steps taken to correct issues. Notes to file can be raised if there is no other document appropriate to record actions taken.
It is important to retain a balance between compliance with the ICH GCP regulations and not over burdening the PI with additional paperwork. However, patient safety and the protection of their rights is the priority for all those involved in clinical trials and so research teams should recognise the importance of this requirement. By identifying the criteria necessary to demonstrate PI oversight early in contract negotiations it allows sites to budget for this in the costings agreement.
As the addendum is recent and uncertainty is prevalent over the evidence required, site staff should be prepared to voice their opinions and rationalise the practicalities of requests to the Sponsor. In turn, the Sponsor has to be prepared to listen to the views of the site and work with them to identify the optimal solution to ensure compliance. It is in both parties’ interests that demonstrating PI oversight becomes routine.
The PI is responsible for delegating responsibilities to the appropriate staff in his team and this should not be taken lightly. The staff should be able to demonstrate that they are qualified and have the necessary experience. The tasks should be adhered to and the team should be able to demonstrate this to an auditor.
At my previous site I discovered that a new research nurse (with only a few months experience) was taking informed consent and asking the investigator to sign the form. This directly contravened the delegation log, yet both the nurse and the PI were happy to disregard ICHGCP. I suggest that it should be part of an inspection that the investigators are required to demonstrate an informed consent to the auditor as a role-playing exercise.
The Sponsor should also be more rigorous in reporting infringements, the same nurse had taken two consents to a Protocol amendment, signing the paperwork herself. The CRA picked up this breach and yet as one consent was not required due patient completion this was not reported to the MHRA. It is only by strict monitoring and enforcing regulations that are in place to ensure patient safety that “loose cannons” can be brought into line. Investigators should view staff that are prepared to violate codes of practice as liabilities, not a way to cut corners and maximise profit. Site sustainability is an ongoing issue, this should be directly related to the quality and transparency of their delivery of clinical trials.
Once again, this comes back to selecting sites that focus on delivering clinical trials transparently and are prepared to account for their actions. As the direct link to the site the CRA’s are vital to communicate their opinions to Sponsors, and their concerns should be taken seriously. There are many great sites with committed, hard-working investigators and they should be recognised and rewarded when it comes to awarding future trials.
