Sponsor Oversight: Legal Responsibility and Industry Best Practice

More than 60% of pharma companies are dependent in some way upon contract research organizations (CROs), according to an analysis from procurement intelligence provider Beroe. This reliance is born in part out of a lack of in-house expertise, as well as a desire to focus on research and development around their therapeutic area and product portfolio. However, pharma companies sometimes forget about the risk they are exposed to when they outsource these activities.

A sponsor’s failure to put adequate processes in place for oversight of CROs and other third parties can result in data integrity issues and critical findings. This can prevent the organization from sponsoring further trials until the issues are resolved. It can potentially lead to delays in the review of a marketing application. It can even lead to additional inspections of investigators, sponsors, and CROs; rejection of an investigational product; application withdrawal; and even criminal prosecution.

The solution to this challenge is simple: when engaging third-party organizations, sponsors must have good processes in place to oversee vendors such as CROs and clinical trial units. Of course, this is more than simply good practice—it’s also a requirement for compliance in many countries.

Sponsor oversight is a legal responsibility, according to the European Medicines Agency’s ICH: E 6 (R2): Guideline for good clinical practice, and needs to be addressed or formally transferred to a vendor, per the FDA’s Title 21 regulations. Sponsor oversight in clinical trials is key to patient rights protection, patient well-being and safety, trial data integrity, reliability of study results, and trial conduct in accordance with good clinical practice and regulatory expectations.

Lack of sponsor oversight leads to data integrity issues

An example of how a lack of sponsor oversight can lead to data integrity issues, including breaches, arose during a discussion at the joint FDA and MHRA symposium on good clinical practices. Inspectors had recently observed a case of unintentional unblinding in a clinical trial. The conducted trial compared the efficacy and safety of an investigational product to placebo in participants suffering from a progressively debilitating disease.

The trial was phase III, multicenter, randomized, and double-blinded. However, the inspectors found that independent evaluators—who were blinded according to the trial protocol and were not involved in any aspect of the participants’ care—were granted access to various electronic systems (eSystems ) used in the trial. These eSystems contained information about laboratory results and cardiac monitoring that could potentially unblind the treatment assignment.

The sponsor had employed a CRO, whose monitors were responsible for providing and revoking access to these eSystems that contained unblinding information. The outcome was that the blinding was not adequately maintained as specified in the protocol, which affected the reliability of the study data and the unbiased determination of treatment response. Furthermore, it showed that the sponsor of the trial failed to demonstrate proper oversight of the monitoring activities.

According to the inspectors, the root cause for the unblinding was multifactorial and the sponsor had:

  • Inadequate protocol-specific training of all personnel.
  • Inadequate processes and procedures to grant and revoke access to these databases.
  • Inadequate processes and procedures to detect inappropriate access.
  • Failure in evaluating monitoring procedures and plans to ensure the monitoring approach was consistent with critical aspects related to data integrity.
  • Failure to communicate relevant information with monitors promptly regarding the first case incident.
  • Failure to maintain adequate documentation to demonstrate their oversight of the monitoring.

How sponsor oversight can be improved

When addressing sponsor oversight, inspectors tend to focus on how well sponsors can detect errors and address data integrity issues. In particular, there is likely to be a focus on the processes and procedures in place for detecting, addressing, and mitigating errors during clinical trials.

FDA suggests a few key ways sponsors can oversee the CRO’s monitoring activities:

  • Establish a clear understanding of responsibilities and expectations for the conduct of monitoring activities.
  • Evaluate monitoring procedures and monitoring plans to ensure the approach is consistent with applicable aspects of the study.
  • Exchange relevant information promptly.
  • Conduct co-monitoring visits as appropriate.
  • Review monitoring reports periodically.
  • Document communication with the CRO regarding monitoring progress and findings.
  • Review metrics routinely.

Finding the right approach

There are many ways that sponsors can improve oversight of vendors and partners, but there is no one-size-fits-all approach. The right approach will depend upon the potential risks and the impact of vendor activities on participant safety and study result reliability.

Want to learn more about this topic? Sign up to watch the recording of our recent webinar Data Integrity in GCP Part 2 – Case Studies, where we dive deep into different aspects of sponsor oversight challenges by presenting different case studies on this topic. Or, for tailored support in creating an effective sponsor oversight strategy for your organization, contact GxP-CC today.

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