ICH Harmonised Guideline for Good Clinical Practice E6(R3) - Step 4 Final

ICH E6(R3) Guideline

3.9.3 The sponsor should determine necessary trial-specific criteria for classifying protocol deviations as important. Important protocol deviations are a subset of protocol deviations that may significantly impact the completeness, accuracy and/or reliability of the trial data or that may significantly affect a participant ’s rights, safety or well being. Decisions related to the trial should be appropriately assessed for their impact on participant ’ s rights, safety and well-being and the reliability of trial results. Risks related to such decisions should be suitably managed throughout the planning, conduct and reporting of the trial. The range and extent of oversight measures should be fit for purpose and tailored to the complexity of and risks associated with the trial. The selection and oversight of investigators and service providers are fundamental features of the oversight process. Oversight by the sponsor includes quality assurance and quality control processes relating to the trial-related activities of investigators and service providers. The sponsor may consider establishing an IDMC to assess the progress of a clinical trial, including the safety data and the efficacy endpoints, at intervals and to recommend to the sponsor whether to continue, modify or stop a trial. Where appropriate, sponsors may also establish an endpoint assessment/adjudication committee in certain trials to review endpoints reported by investigators to determine whether the endpoints meet protocol-specified criteria. To minimise bias, such committees should typically be blinded to the assigned treatments when performing their assessments, regardless of whether the trial itself is conducted in a blinded manner. Committees established for purposes that could impact participant safety or the reliability of trial results should include members with relevant expertise and with managed conflicts of interest, have written operating procedures (e.g., charters) and document their decisions. The sponsor should implement an appropriate system to manage quality throughout all stages of the trial process. Quality management includes the design and implementation of efficient clinical trial protocols, including tools and procedures for trial conduct (including for data collection and management), in order to ensure the protection of participants ’ rights, safety and well-being and the reliability of trial results . The sponsor should adopt a proportionate and risk based approach to quality management, which involves incorporating quality into the design of the clinical trial (i.e., quality by design) and identifying those factors that are likely to have a meaningful impact on participants ’ rights, safety and well-being and the reliability of the results (i.e., critical to quality factors as described in ICH E8(R1)). The sponsor should describe the quality management approach implemented in the trial in the clinical trial report (see ICH E3 Structure and Content of Clinical Study Reports). 3.9.8 3.9.9 3.10 Quality Management 3.9.4 3.9.5 3.9.6 The sponsor should ensure appropriate and timely escalation and follow-up of issues to allow the implementation of appropriate actions in a timely manner. 3.9.7

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