What approach does the ICH E6(R2) integrated addendum require sponsors to use in managing trial quality?

The ICH E6(R2) integrated addendum recommends a risk-based approach for managing trial quality. This approach emphasizes identifying and minimizing risks to participant safety and data integrity throughout the clinical trial process. By focusing on the most significant risks, sponsors can allocate resources more effectively, ensuring that critical aspects of the trial are monitored closely while maintaining flexibility in less critical areas.

This risk-based strategy involves systematic assessment and management of risks from the planning stage up to the trial’s conclusion. It empowers sponsors to implement specific risk mitigation measures, which can include adaptive monitoring and focusing quality assurance efforts where they're most needed. This not only enhances trial integrity but also aligns with regulatory expectations for ensuring that clinical trials are conducted ethically and efficiently.

The other approaches mentioned do not align with the ICH E6(R2) standards. A penalty-based approach would not necessarily address risks proactively and could lead to a culture of fear, which is counterproductive to open communication and transparency in clinical trials. A random selection approach lacks focused risk management, failing to address specific vulnerabilities in the study’s design or implementation. Lastly, a retrospective review approach occurs after data collection and may miss critical issues during the trial, making it less effective for ongoing quality assurance and participant safety oversight.