In theory, the relationship between CDISC’s SEND Implementation Guide (IG) and the FDA’s study data Technical Conformance Guide (TCG) is pretty straight forward: CDISC defines the IG and then the TCG communicates “general considerations on how to submit standardized study data using FDA-supported data standards located in the FDA Data Standards Catalog” (section 1.1).
The IG states how to standardize data and the TCG talks about the submission requirements of those standardized data. So, the IG leads with the standardization and the TCG follows with the submission requirement. However, recently it feels like things are working the other way around, with the IG development following the direction laid out by the TCG.
Let’s talk about a few specific examples. In SEND 4.0 the BG (bodyweight gain) domain is being removed as a direct consequence of the TCG stating “It is not necessary to include a BG domain in submissions” (section 4.1.3.3).
In 2017, the agency added a section describing the specific variable population for PC (pharmacokinetic concentrations) needed to allow the agency to produce the visualizations and perform their analysis. This was to overcome an issue identified after the SEND 3.1 Fit-For-Use pilot, where the agency struggled with these data. This then led to the development of SEND 3.1.1 which brought the PC domain in line with the recommendation in the TCG. This is why the FDA’s study data catalog currently allows for either SEND 3.1 or SEND 3.1.1 to be used for submission, because when SEND 3.1 follows the TCG there should be no real difference between these versions.
Then in September 2021, the agency added the Scope of SEND text (section 4.1.3.4) which stated that certain juvenile studies were required for submission, despite no examples or guidance having been published for such studies. This led the CDISC DART team to pivot away from our planned work to quickly produce SENDIG-DART v1.2 to include such examples and guidance. These examples were required because juvenile studies require data to be analyzed by age rather than by study day or by the number of days exposed.
Most recently, a new TCG was issued which further widened the scope of SEND for DART to include combination studies. Studies where only a certain period of study could be represented in the current SEND modeling. Again, no examples or guidance currently exist to describe how to handle such studies. So again, the CDISC DART team has pivoted, and we are working on quickly producing the necessary examples and guidance. This time, we are not looking to publish a new version of the IG with this information but are looking for a more immediate publication method.
I started this post with the theory that the IG leads and the TCG follows, but here we’ve looked at specific examples where the IG is playing catchup to the TCG. I guess that just shows that the relationship between the SEND Implementation Guide and the FDA’s Technical Conformance Guide has become more symbiotic than we previously anticipated.
‘til next time
Marc
