There have been rumors of a proposed Nervous System domain (NV) for many years, yet still nothing has been published and it’s not listed in the content for SEND 4.0. So, just what is going on?
At the recent joint FDA and CDISC SEND meeting, the full scope of SEND 4.0 was presented, and so in my last post I described that content (read it here), and I mentioned my frustration that we still won’t have a dedicated domain for representing CNS data such as Functional Operation Battery (FOB) and Irwin Tests.
Following on from that post, I thought it would be a good idea to discuss some of the checkered history of SEND and the elusive NV domain. It was originally created for inclusion in SEND 3.1, which was published back in 2016. It then came close to inclusion in SENDIG-DART 1.2 but again was pulled late in the process. SEND 4.0 is planned to be published in 2023, yet NV still didn’t make the cut.
At the moment, the intention is for it to be included in a dedicated Safety Pharmacology Implementation Guide (SENDIG-SP), due for publication in 2025. Assuming that all goes to plan, that’s nearly a full decade later than originally expected when it was written.
So, why has it been continually delayed? The main issue cited is disagreement on how to represent the full list of available values. Clearly, in order to make use of the data, the scores and values themselves are not sufficient, we need the context. We need to know what values were available for the assessment. Personally, I’ve always advocated that the Define-XML file should be used for this. Many don’t like using the Define file due to incompatibility with Excel. There were suggestions for inclusion in the nonclinical Study Data Reviewer’s Guide (nSDRG), but the counter arguments were overwhelming.
So, some have driven ahead with a solution to have a dedicated domain in SEND called Scoring Scales (SX), housing lists of all available values for such assessments. NV was removed from SENDIG-DART 1.2 for juvenile studies because it needed the SX domain for the scoring scales. With SX now included in SEND 4.0, why do we still not have the NV domain?
The answer given is that nervous system tests are predominantly used in Safety Pharmacology, and as such belong in their own IG (SENDIG-SP) and not the main SEND IG, which is now supposed to just focus on general toxicology. So, “what about the domains for ECG, cardiovascular and respiratory?” I hear you ask. Good point. They will still be in SEND 4.0, but without NV.
Having dredged over the history and issues, I come back to the statement in the FDA’s Technical Conformance Guide “Overall, the expectation of SEND datasets for nonclinical studies is linked to the pharmacological and toxicological information required to provide FDA with the data needed to assess and support the safety of the proposed clinical investigations” which then goes on to talk about how SEND is needed to “…assess the risks to human subjects…”.
As the nervous system data can be vital to the safety assessment, shouldn’t we include it in SEND? If we needed to do that, without the NV domain, what other options do we have? Maybe that becomes the topic of a future blog.
I know feelings vary on this topic, so if you’d like to continue this conversation with me, just drop me a note at email@example.com
‘til next time