Last week was the Fall 2022 CDISC meeting. As usual, the highlight of the meeting was the public joint presentation between CDISC and FDA. With each event, cross study analysis has slowly become more of a focus. This time, there were multiple presentations referring to this topic and the opportunity to use SEND beyond just FDA compliance.
The meeting began with a presentation on behalf of Japan Pharmaceutical Manufacturers Association (JPMA). While many interesting points were raised, probably the most thought-provoking topic was the discussion around the use of virtual control groups. While this is an idea that has occasionally been mooted in nonclinical safety assessment circles, it was fascinating to see it being stated in relation to SEND. JPMA stated quite clearly that they understand this is a highly controversial suggestion. According to the presentation, this was partly driven by the 3Rs, but also noted that there is difficulty in obtaining certain types of subjects. They also stated that “In clinical field, there is a movement to replace the placebo control group with historical control and/or real world data”. Carrying this principle into nonclinical will certainly provoke some interesting discussions!
Regarding the development and expansion of the SEND standard, the single biggest piece of news to drop from CDISC was the fact that the next version of the SEND Implementation Guide will be called version 4.0 and not version 3.2 as previously communicated. What is the significance of this? CDISC leadership stated that they wanted to communicate that this release includes quite substantial changes. There will be 5 new domains available:
- Pharmacokinetic Input (PI)
- Scoring Scales (SX)
- Cell Phenotyping (CP)
- Immunogenicity Specimen Assessments (IS)
- Ophthalmic Examinations (OE)
This version will also drive a new version of the underlying SDTM model as 18 new variables are being added across the guide.
In addition to SEND 4.0, work continues with both the SENDIG-DART 1.2 for juvenile toxicology and SENDIG-GT 1.0 for genetic toxicology. Both standards have made good progress towards their 2023 publication dates. It’s also worth mentioning that good progress is also being made by the Tumor Combinations working group which is creating, publishing and maintaining recommendations for combining tumors for analysis in nonclinical using SEND Controlled Terminology.
Finally, the event concluded with an excellent presentation from the BioCelerate – FDA CDER SEND Harmonization/Cross Study Analysis Working Group who are looking to use SEND for cross study analysis in relation to the Target, and specifically “Understanding off-target toxicity”. The presentation included several novel visualizations that they have developed specifically for this application of cross study analysis.
While this joint presentation was the highlight of the week, significant progress was being made by all the CDISC SEND workstreams. I think that many involved will agree that it was an exhausting but very productive week.
‘til next time