Narratives for Adverse Dropouts in the CSR

Question 1:

I am confused about the requirement to include (or not include) narratives (and CRFs) for subjects who discontinue investigational product/dropout due to an adverse event (“adverse drop outs”) in the clinical study report. Are these narratives specifically required in the study report? From the `Good Review Practice' document for conducting safety reviews one would gather that these events are important to the safety review but a strict reading of ICH E3 would indicate they are not required - can you please clarify?

Answer 1:

The ICH E3 guideline requires narratives for certain adverse events. Note that section 12.3.2, "Narratives of Deaths, Other Serious Adverse Events, and Certain Other Significant Adverse Events," states that, "There should be a brief narrative describing each death, other serious adverse event, and other significant adverse event that is judged to be of special interest because of clinical importance...."

Note that in the introduction to section 12, the guideline states, "For the purpose of this guideline, 'other significant adverse events' are marked hematological and other laboratory abnormalities and any adverse events that led to an intervention, including withdrawal of drug treatment, dose reduction, or significant additional concomitant therapy."

The ICH E3 definition of "other significant adverse events" would include "adverse drop outs" and thus a narrative should be provided. If you have concerns about the need for narratives in a clinical study report for a specific study, you should contact the appropriate FDA review division.

Search the FDA-GCP database
© 2003-2018 First Clinical Research LLC.  Trademark Notice  Terms & Conditions  Privacy Statement  Site Map