What can we do? Answers from CSS Nonclinical Topics WG Follow up activity to “Nonclinical: Bringing it all Together” presentation by Dr. Lilliam Rosario What can we do? Answers from CSS Nonclinical Topics WG

Content This presentation summarizes the CSS Nonclinical Topics Introductory activity, in which Dr. Lilliam Rosario (Director, Office of Computational Science, FDA) asked: “What can we do to help?” regarding the e-data submission review processes and nonclinical PhUSE projects Each idea was written on a post-it note and stuck to a poster (see picture on title slide) describing e-data submission, processing and use by reviewers. The ideas are listed (verbatim) with “@....” To indicate where on the poster the idea was posted. The attendees of CSS then reviewed the list and either answered, or made recommendations on how to address the idea. Recommendations are listed on Slide 6.

Post-it ideas @CDISC: Need ability to generate tabulated summaries leveraging SEND data @Define: Where should information be submitted? Nonclinical SDRG and Define file? Does information need to be duplicated? Industry index of where to find information? Define usability, what is needed/helpful? Keys? Dictionary/codelists? @graph: Validation results – warning/errors, consistency, interpretation? Some sponsors not generating the datasets/CROs are doing it for them, that results in sometimes in negotiations – efforts to align this would be valuable. @scripts assessment: Visualization: we would like to see the data the way you see it.

Post-it ideas @Visualization: Expand visualization to capabilities to other data types Controlled terminology for histopath and clinical signs; MedRA into clinical @Tables: is there a need to create group comparison stats and summary tables from SEND for reviewers? @Kick-start: Checks for conformance and consistency before Kick-start? Sharing feedback from technical implementation (FDA to Public) Sharing anything from FDA on what hinders reviews: something like “hot issues” per quarter to public @Modeling Endpoints “Flow if possible” Define File: what is the usage in SEND Cross Domain Visualization Rational plan for standards development, testing, implementation, sunsetting. Input for next cycle. SDRG.XML and Define.xml: Can this be one deliverable, usable by all? Provide a mechanism whereby the reviewers routinely communicate their review experience and suggestions for improvement to the sponsors.

Breakout Discussion Outcome Post-it Ideas NCT WG Recommendation Need ability to generate tabulated summaries leveraging SEND data Possible PhUSE Project Industry index of where to find information? Refer to SEND Implementation User Group for assessment Define - usability, what is needed/helpful? Keys? Dictionary/codelists? Define File: what is the usage in SEND Where should information be submitted? Nonclinical SDRG and /or Define file? Refer to Define Codelist project team for bullet one. FDA will provide more information regarding the use of the define file for nonclinical studies. Then refer to nsdrg project team for recommendation on where info should be submitted. Validation results – warning/errors, consistency, interpretation? Some sponsors not generating the datasets/CROs are doing it for them, that results in sometimes in negotiations – efforts to align this would be valuable. Nsdrg and Csdrg project team will work on representation of validation in SDRGs. Possible PhUSE project to align CROs and Sponsors interpretations of warnings and errors. Visualization: we would like to see the data the way you see it. FDA to take this under advisement. Expand visualization to capabilities to other data types Cross Domain Visualization Visualization of Histopathology team and Scripts team are interested in new ideas . Possible new PhUSE project for specific visualization goals. (as done for histology) Controlled terminology for histopath and clinical signs; MedRA into clinical Histopath has CT for non-neoplastic findings, specimen, etc. General agreement that controlling clinical signs and mapping to MedRA are not very valuable for nonclinical. is there a need to create group comparison stats and summary tables from SEND for reviewers? No. Checks for conformance and consistency before Kick-start? Conformance and data consistency (i.e. number of noses) is expected from Sponsors. Sponsors should assure the accurate representation and format of the data. Sharing feedback from technical implementation (FDA to Public) Sharing anything from FDA on what hinders reviews: something like “hot issues” per quarter to public “Flow if possible” Possible new PhUSE project (Like ADA) to explore representing flow cytometry data in SEND. Rational plan for standards development, testing, implementation, sunsetting. Input for next cycle. Refer to CDISC SDRG.XML and Define.xml: Can this be one deliverable, usable by all? Pending answer from FDA on how define is used. Provide a mechanism whereby the reviewers routinely communicate their review experience and suggestions for improvement to the sponsors.