Question 20 of 20 Advanced Concept
What role does the reference safety information play in a development safety update report?
Short answer
The reference safety information, usually the investigator's brochure version in effect at the start of the reporting period, is the yardstick for deciding which reactions are expected. The DSUR states that version and judges the year's safety data against it, so a mid-year brochure update does not change what counted as unexpected during that period.
Why
ICH E2F sets the development safety update report (DSUR) as an annual report on a drug in development, and EMA notes that US and EU regulators accept it in place of the US IND annual report and the EU annual safety report. The year starts from the development international birth date, the first authorization to run a trial anywhere, and the data lock point is the last day of the year. Section 2.6 says the investigator's brochure in effect at the start of the period serves as reference safety information, and the DSUR must state its version and date.
This matters because expectedness drives expedited reporting. A reaction not in the reference safety information is unexpected, and if it is also serious and suspected, it is a SUSAR. Fixing the yardstick at the start keeps the year's assessment consistent and stops a company from adding a reaction to the brochure halfway through and then calling earlier cases expected.
Changes to the reference safety information during the period are reported in their own DSUR section.
A strong answer covers
- DSUR purpose and annual cycle from the development international birth date
- Brochure version at the start of the period as reference
- Expectedness drives SUSAR reporting
- Changes during the period reported separately
- Replaces US IND annual report and EU annual safety report
Common mistakes
- Using the latest brochure to judge expectedness for the whole year.
- Confusing the DSUR with the postmarketing PSUR.
- Listing every adverse event in the reference safety information, which hides true unexpected reactions.
The interviewer might ask next
How would you decide whether a newly observed reaction should be added to the reference safety information?