What’s New in E6 R3? Sponsor Responsibilities, Part 3 – Sponsor Oversight

The word “oversight” is a contronym, with two meanings that are the opposite of each other:

• Watchful supervision (e.g., “We maintained oversight of our CRO”)
• Omission or error due to lack of watchful supervision (e.g., “Due to an oversight, we did not register our trial on clinicaltrials.gov in a timely way”)

Contronyms are sometimes called “Janus words,” after the Roman god of doors and gates, for whom the month of January is named.

ICH GCP E6 R3 features a new section on Sponsor Oversight that emphasizes the first meaning of the word.  This section hits some of the highlights from R2 (risk and compliance) while including some updated references regarding protocol deviations and committees.

The whole enchilada.  The section starts with a general statement that sponsors are responsible for ensuring that trial design, conduct, processes, data and documentation are of sufficient quality to ensure participant safety, reliability of results, and appropriate decision-making.

Compliance.  The sponsor is responsible for ensuring that the trial is conducted per the protocol, study-specific plans, and regulations. Toward that end, the sponsor should determine trial-specific criteria for identifying “important” protocol deviations, or those deviations that impact the rights, safety, or well-being of participants or the reliability of results.  In R2, the term “important deviation” was used in conjunction with risk reporting, with a reference to ICH E3, Structure and Content of Clinical Study Reports. The mention of “trial-specific criteria” is key, because many sponsor utilize the “example” criteria in E3 (“such as” eligibility, withdrawal, dosing, and excluded concomitant treatment deviations) as their standard criteria for important deviations, when study-specific criteria might be more appropriate.

Risk management.  Decisions should be assessed for risks.  Oversight measures should be tailored toward risk level, with a note that selection of investigators and service providers is the foundation of oversight. Issues should be escalated and followed up in a timely manner. Risks should be actively managed throughout the trial.  These statements appeared in R2 in conjunction with risk management, but the statement tying oversight to risk is new. As we noted in an earlier post, R2 also did not include requirements for qualifying vendors, which are reiterated here.

Committees.  The sponsor may establish an Independent Data Monitoring Committee, Endpoint Adjudication Committee, or other committees for other purposes.  Committees activities should be guided by written charters and should be “managed” for conflicts of interest.  Adjudication committees should be blinded to treatment assignments.  R2 previously referenced Independent Data Monitoring Committees and investigator coordinating committees, but not other types of committees.