There’s been some significant news since my last blog post. Firstly, the FDA released a new version of the study data Technical Conformance Guide (TCG), and then we had the combined CDISC and FDA public webcast where some major changes to SEND 4.0 were announced.

The biggest update to the TCG was the addition of a section describing the scope of SEND for SENDIG-DART for CDER submissions. At the public webcast, the FDA then gave a presentation going through this update in more detail. The new section is very similar to the existing section for SEND 3.1/3.1.1. The usual verbiage is present regarding the GLP status, the drug substance, etc. and how such factors do not impact whether or not SEND is required. No surprises there.

The interesting text comes a little later. This starts with a very specific statement that preliminary studies (smaller scale studies) which are used in lieu of a regular study for assessing clinical safety, are in scope. This makes perfect sense and is hardly unexpected.

Studies which are used to determine dose levels or dose schedules for a SENDIG-DART study are not required in SEND. The reasoning being that such studies do not impact clinical safety. It’s great to see this explicitly stated.

The surprises then come in the next sections:

Combo studies are in scope. Combo fertility/EFD and combo EFD/PPND studies are required in SEND, at least for the EFD portion. I’m calling this a surprise, but is it really? The equivalent section for SEND 3.1/3.1.1 has always described the situation, “When general toxicity studies incorporate other study types…”, however, the examples provided are where both study types are already in scope for SEND (it gives the example of general tox combined with cardiovascular). Still, the implication is the principle can be applied when two study types are combined: the general tox study design is in scope. Put in SEND what can be put in SEND and document the rest.

So now we have this principle applied to SENDIG-DART. However, for such studies, this is potentially more troubling. It’s not a case of simply omitting certain endpoints. We are potentially talking about omitting entire phases of the study. While this is quite possible to achieve, what concerns me is that this could be interpreted in different ways, resulting in inconsistent representation of similar studies from one organization to the next. For this reason, I believe that we need good guidance and examples to be produced as soon as possible.

The TCG also specifically called out enhanced PPND studies. These are studies where many of the same endpoints could be collected via the use of something like an ultrasound. The agency is stating that such studies are not required in SEND at this point. However, they do state “voluntary submission of these datasets is encouraged”. They are asking for SEND, but not requiring SEND. Does this mean they will make them required in the future? Maybe.

One thing that I don’t think is stated in the TCG, but was called out in the webcast, is that SENDIG-DART studies starting prior to the 15th of March 2023 currently do not require a simplified ts.xpt. Obviously, this is a significant difference to SEND 3.0/3.1/3.1.1 studies. The reason is that the technical rejection for SENDIG-DART doesn’t exist yet. The implication here is that this situation may change in future.

My 500 words are up and we didn’t get time to talk about the changes to SEND 4.0. Come back next time where I’ll discuss those.

‘til next time


Published by Marc Ellison

Self-confessed SEND nerd who loves geek-ing out about everything to do with SEND. Active CDISC volunteer and member of the CDISC SEND extended leadership team. Director of SEND solutions at Instem responsible for all our industry leading SEND products and services.