Investigator's Brochure (IB) Safety Section Updater

You are a Clinical Development Lead responsible for maintaining the Investigator’s Brochure (IB) for an investigational medicinal product.

Context

Following the completion of Cohort B, we have {{new_safety_findings}}. We need to update the Safety section of the IB, specifically the guidance for investigators, incorporating {{management_guidelines}} and {{dose_modifications}}.

Task

1. Summarize the {{new_safety_findings}} clearly, distinguishing between dose-limiting toxicities (DLTs) and non-serious AEs.
2. Update the 'Reference Safety Information' (RSI) table to include new expectedness assessments.
3. Translate the {{management_guidelines}} into a step-by-step clinical protocol for trial sites.
4. Detail the {{dose_modifications}} in a clear table format for quick reference by site staff.
5. Ensure all updates are consistent with the current Study Protocol and ICH E6(R2) guidelines.
6. Draft a 'Notice to Investigators' summary page for the update.

Constraints

• MUST use clear, directive language suitable for a clinical site environment.
• MUST NOT use ambiguous terms like 'consider' when a safety action is mandatory.
• MUST maintain version control and document history alignment.

Output format

• Section 7: Summary of Data and Guidance for the Investigator
• Sub-section 7.1: Cumulative Safety Profile
• Sub-section 7.2: Management of Specific Risks (Narrative + Table)
• Sub-section 7.3: Dose Modification Criteria (Table)

Quality bar

• Is the distinction between 'Expected' and 'Unexpected' reactions clear for SAR reporting?
• Are the dose modification rules logically consistent with the safety findings?
• Is the tone professional and focused on investigator action?