In the next installment of our series on what's changed between the May 2023 draft and January 2025 final versions of ICH GCP E6 R3, we tackle section 3.15, Safety Assessment and Reporting. There are not too many changes here, as Safety is a fairly well-established aspect of GCP.
Step 3.13.1 on sponsor review of safety information previously stated that the sponsor should "aggregate, as appropriate, and periodically review relevant safety information." The final version now states that the sponsor should "aggregate, as appropriate, and review in a timely manner relevant safety information," indicating that triggers should be in place to review urgent information even when outside of the periodic review cadence.
Step 3.13.2 (b), which describes expedited reporting, formerly stated that sponsors should "expedite the reporting to regulatory authority(ies) of all adverse drug reactions (ADRs) that meet three criteria: suspected, unexpected and serious (i.e., SUSARs)." It now states that sponsors should "expedite the reporting to regulatory authority(ies) of all suspected, unexpected and serious adverse reactions (i.e., SUSARs)." We think the wording was clearer in the draft version and more consistent with the Glossary, which defines a SUSAR as "an adverse reaction that meets three criteria: suspected, unexpected and serious." A person unfamiliar with the SUSAR criteria could potentially interpret the new statement as "expedite reporting of all suspected adverse reactions, all unexpected adverse reactions, and all serious adverse reactions," which is a much larger reporting volume.
This change illustrates an issue we see often in clinical research: Wording in protocols and plans that is imprecise, but is interpreted (mostly) consistently by readers because they know what it's supposed to say. This always reminds us of Alice in Wonderland:
"Then you should say what you mean," the March Hare went on. 'I do,' Alice hastily replied; "at least—at least I mean what I say—that's the same thing, you know." "Not the same thing a bit!" said the Hatter. "Why, you might just as well say that 'I see what I eat' is the same thing as 'I eat what I see!'
