ZEPHYR-101 LATE CHANGE REQUEST (SYNTHETIC)
Fictional study and fictional product ZX-204. Not real data.

Request date: 1 October 2026
Requested by: biostatistics
Status: submitted, not yet assessed

SUMMARY OF THE REQUEST
Add a pre-specified sensitivity analysis of the primary endpoint that excludes participants who had a major protocol deviation affecting the primary assessment. The statistical analysis plan currently has no such analysis.

WHY NOW
A reviewer comment on an earlier draft of the clinical study report asked whether results are robust to major protocol deviations. Biostatistics believes the analysis should be added before database lock rather than after unblinding.

WHAT IS KNOWN
- A protocol deviation dataset exists, but the definition of "major" was finalized only last month.
- The primary endpoint analysis dataset would need a new population flag.
- One summary table and one figure would be added.
- Biostatistics estimates the programming effort at "a few days".
- No one has yet checked whether the new flag affects other analyses that share the same population.

WHAT IS NOT KNOWN
- Whether the sponsor has approved an amendment to the analysis plan.
- Whether independent QC capacity exists for the new work before the date for the second dry run.
- Whether the reviewer guide needs to describe the new flag.
- Whether the change should be implemented in the shared analysis dataset or only in the new output.

REQUESTED DATE
Include in the second dry run on 22 October.