Next in our analysis of ICH GCP E6 R3 - a review of the expanded Safety Assessment and Reporting section.

R2 previously included information about safety reporting in two sections:  Safety Information and Adverse Drug Reaction Reporting.   This section included five points:

• The sponsor is responsible for ongoing safety evaluation.
• The sponsor should promptly notify all parties of findings that could affect the safety of study subjects
• The sponsor should report serious unexpected suspected adverse drug reactions (SUSARs) to investigators, IRBs/IECs, and regulatory authorities, where required
• The sponsor should submit all required safety updates and periodic reports as required by regulatory authorities.

R3 has been revised to reflect a much more robust picture of safety activities, specifying these additional sponsor responsibilities:

• Periodic  safety evaluation of aggregated data on the investigational product, with updates to the protocol, Investigator's Brochure, informed consent forms, and other material and communication to stakeholders
• Expedited reporting of SUSARs to investigators and IRBs/IECs "in a manner that reflects the urgency of action required."
• Reporting of urgent safety issues to regulatory authorities, investigators, and IRBs/IECs "without undue delay."
• Pre-definition of "alternative arrangements" in the protocol after obtaining agreement from regulatory authorities and IRBs/IECs and described in the protocol. This point references ICH's E19 guideline, A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-Approval or Post-Approval Clinical Trials, which outlines types of safety data that may be appropriate for "selective" (i.e., reduced) collection, including non-serious adverse events, laboratory and imaging assessments, physical exam and vital sign data, and changes in concomitant medication use throughout the trial.
• Steps to address immediate hazards to participants, including protocol amendments and communication with IRBs/IECs.  Note that R2 specified this as an investigator responsibility; R3 includes this step in the Investigator Responsibilities section but adds the sponsor responsibility here.