Editor’s Note: The document referenced throughout this article is the ICH eCTD STF Specification V 2.6.1.
A number of sponsors have recently inquired as to the proper use of the modified-file attributes (operators) when using Study Tagging Files (STFs). Our research has yielded a number of helpful findings on the subject.
The Lifecycle Management section (page 10) of the latest ICH guidance on eCTD Backbone Files Specification for Study Tagging Files incorrectly states that the modified-file attribute of “append” is used to control lifecycle operations of that STF. While the documentation is wrong we don’t expect a timely update.
As per FDA requirement the modified-file attribute does not control lifecycle management. In actual practice, STF lifecycle management is controlled by assigning the same CTD section, study ID and categories.
Lifecycle management of STFs is documented in the FDA specification for eCTD Validation Criteria as error 1850. Error 1850 was introduced in version 1.0 of this document effective March 10, 2008, and error 1850 is present in the latest version (3.1) dated February 7, 2014. The guidance document warns that “if you have appended an STF with a second STF, and the two study IDs are different (not an exact match), the reviewer will see two studies instead of one.”
It is important to note that the eCTD Validation criteria makes no recommendation as to whether or not the modified-file operation should be used, and does not classify doing so as an error. Accordingly, you cannot update the category [or study ID] as the guidance states in the section on Modifying STF Information (page 11) and shows in the Example Scenario Sequence 0002 (page 20).
Also, in practice, if two STFs are submitted to the same CTD section, study ID and categories (e.g. species), whether they are submitted in the same sequence or different sequence, those STFs will appear as one study to the reviewer – contradicting the Study Data Management Options of the STF specification (page 16).
What does this all mean to you?
You need to confirm that the publishing and review software you are using to manage the lifecycle of studies is based on having the same CTD section, study ID and categories – not the modified-file operation.