Sponsor Oversight - Metrics & Case Studies

In our previous News about the MHRA blog on Sponsor Oversight  we reported on the different mechanisms by which oversight can be demonstrated. The Sponsor maintains overall responsibility for the conduct and reporting of the trial. Thus, mechanisms should be in place to demonstrate oversight of activities contracted or delegated to ensure patient safety and data integrity. Recently, the MHRA posted Part 2 of the blog which provides some metrics together with two case studies from recent GCP inspections in regard to Organization’s Oversight of Clinical Trials.

According to the agency, during the period of 2015 - 2016 three critical findings were observed (all at non-commercial organizations). A total of ten major findings were found (nine at non-commercial organizations and one at a commercial organization). During the period before twelve major findings were observed (six each at commercial and non-commercial organizations). More recently, during the period 2016- 2017 there was one critical finding for ‘Organization’s Oversight of Clinical Trials’ which was identified at a non-commercial organization and two major findings (one each at commercial and non-commercial organizations). The blog states: "It would appear that compliance is improving in this area, but many factors can influence these metrics such as the total number and types of inspections performed during the year".

Additionally, two case studies have been presented:

1) Non-commercial organization:

The following critical finding was observed in case of a sponsor due to lack of oversight of trials managed by the Clinical Trial Unit (CTU) and Chief Investigators (CI) which resulted in critical compliance issues with pharmacovigilance in one of the sponsored trials:

• The Quality Management System (QMS) lacked key procedures required to ensure oversight of trials and there was no assessment of the CTU´s QMS for those trials managed by the CTU.
• Trial Master File (TMF) / Investigator Site File (ISF) audit were the only types of audits performed and the QA Manager lacked experience in performing audits.
• Contracts and agreements were missing with key vendors or lacked detail.
• Delegation of duties to the CI and CTU were not adequately detailed or completed.
• The Sponsor did not have sight of key documents or changes to documents (e.g. the Reference Safety Information, RSI) for trials to ensure continued oversight of trials.

2) Commercial Organization

A major finding for "Organization’s oversight of Clinical Trials" was identified for the following:

• No evidence to demonstrate the sponsor oversight activities as specified in the CRO’s (Contract Research Organization) plans (for example oversight of approvals).
• Co-monitoring visits were not performed in accordance with the monitoring oversight plan (lack of co-monitoring visits performed and when performed they had not been reviewed as required).
• Inadequate documentation to demonstrate when MVRs (Monitoring Visit Reports) created by CROs were reviewed, by whom and the outcome of the review.
• Inadequate documentation to demonstrate review of protocol deviations occurring in the trials.
• Lack of oversight of TMFs held by vendors to ensure they were up to date and complete.
• Late reporting of SUSARs (suspected unexpected serious adverse reaction) by the CRO, which the sponsor did not have oversight of.
• The TMF index did not specify the sponsor oversight file. It was not possible to reconstruct how the sponsor maintained oversight of the CRO and how the trial was being conducted. During a subsequent investigator site inspection, a number of major findings were identified which had not been detected through monitoring and of which the sponsor was not aware.