What’s New in E6 R3? Data Governance

The new Data Governance section in ICH GCP E6 R3 applies to data integrity, traceability, and security for both investigators and sponsors.  The section starts with some general principles and then proceeds to eight numbered sub-sections.  This section is significant, as it addresses controls for electronic medical records for the first time in GCP. Here are the highlights:

General principles.  The “quality and amount” of information generated in a clinical trial should support the trial’s objectives, provide confidence in results, and support good decision-making.  Accordingly, investigators and sponsors should put processes in place to ensure protection of confidential data; validation of computer systems; safeguarding of randomization, blinding, and dose escalation; and analyses that will support decision-making.

Blinding. Blinding should be protected throughout key activities, such as providing sites access to data, data transfer, and data review.  Roles, responsibilities, and procedures for accessing unblinded information should be defined.  Potential for accidental unblinding should be considered as part of the risk assessment, and any unblinding prior to the final analysis should be documented and assessed for its impact on results.  Some of these points were also made in the Statistical Programming and Data Analysis subsection of the Sponsor Responsibilities/Data and Records section of R3.

Data Life Cycle Elements.  This subsection describes procedures that should be in place over the full “data life cycle,” which includes data capture, metadata capture, review, corrections, transfer, and finalization. Key points:

• Data capture, verification and validation should take a risk-based approach, based on data criticality.
• Acquired data should be accompanied by relevant metadata.
• Audit trails should log user data (account creation, role/permission changes, and access)
• Audit trails should include reason for change, unless it’s implicit; if implicit, the decision not to capture it should be documented in a risk-based evaluation
• Any situation in which audit trails are disabled or modified (e.g., for a “back-end change”) should be documented and justified
• Date and time stamps should be unambiguous (e.g., captured in UTC)
• The system owner should determine which metadata require review and retention
• Audit trail and metadata review should be planned and risk-based
• Corrections to data that could impact reliability of study results should be attributable, justified, and “supported by source records around the time original entry”
• Pre-analysis data cleaning activities should be documented, including data reconciliation, corrections, coding, “compilation,” and steps to address the impact of protocol deviations

Computerized Systems. The introduction to this section clearly states that sponsors should review electronic medical records systems and other electronic systems used by sites to determine whether they are “fit for purpose” in the context of the trial.  All systems must be secure, validated, change controlled, and supported.  Users should be trained and follow written procedures for using systems. User access should be controlled.