November’s trip out to the American College of Toxicology Annual Meeting (ACT) was my first time back at the conference since you-know-what brought the world to a standstill. It’s really fascinating to see how much the SEND conversation has moved on in that time. It certainly was a hot topic for discussion, but we’ve left behind the questions of “do I really have to do SEND?” and moved on to discussions about the additional value can we pull from SEND datasets. There was an afternoon’s symposium entitled Cross Study Analysis and Visualization Using SEND Data, which was co-chaired by Wenxian Wang of BMS and Mark Carfagna of Eli Lily. Anyone who’s dipped even the slightest of toes into the waters of SEND cross study analysis and visualization will be very familiar with Mark, as he’s been a leading voice in this area for some time.
One part of the symposium was an intriguing presentation by Susan Butler of FDA CDER, who explained techniques for comparing studies that vary by factors such as species or sex. In such cases, the typical values for results like bodyweight can differ wildly from species to species.
The technique of calculating and using a Zscore was explained and demonstrated. Without going into detail and explaining all of the formulas, the basic concept is that a score is assigned based on differences from the control group using standard deviations from the mean to normalize the data. Effectively, this means that we see a numeric score of the significance change that the compound is producing, and these scores are comparable from one study to the next despite the fact that the individual measured values can be vastly different.
This presentation was just one example of the developing interest in using our standardized nonclinical data for something beyond submission. That said, we did still hear the comment that SEND was just an additional “submission tax”, however such opinions are now seeming to be slipping into the minority as many organizations are starting to explore other uses of the SEND data.
Having returned from ACT, and while looking ahead to 2024, we saw the unexpected posting of a Federal Register Notice indicating that (among others) SENDIG-GeneTox v1.0 will become a submission requirement from March 15th, 2025. Not only did the posting take me a little by surprise as I’d assumed the agency may first run a Fit-For-Use pilot, as they did with SENDIG-DART, but we are also seeing the FDA start to require a new standard with just over one year’s notice to industry. Previously, a requirement for a new standard has come with at least two years notice, and updates to existing standards being one year. In fairness, this shouldn’t exactly be too taxing on industry as this new standard only contains a single new domain, which itself contains no new variables.
At Instem, we’d already started work on planning our implementation of SENDIG-GeneTox v1.0, as our own Mike Wasko led the CDISC team which produced this new SEND Implementation Guide.
So, it was great to return to ACT and see that people are now more focused on the uses of SEND beyond submission, as well as seeing the scope of SEND widening further as we close out the year.
Season’s greetings to you all, and I’ll be back in the new year.
‘til next time
Marc
