1. CDISC SDS Oncology Domains: An Orientation to Aid Review & Feedback Barrie Nelson CDISC SDS Oncology Sub Team Lead 2010-02-01

2. Agenda Purpose of this Presentation The Documentation Package The Development Team Purpose & Rationale An Overview of the proposed domains –TU : Tumor Identification –TR : Tumor Results –RS : Response Solicited Feedback Review Comments Next Steps

3. Purpose of this Presentation The assessment of the FDA Review Divisions as to whether the proposed domains are fit for their intended purpose is an essential element in the development of these TA specific SDTM domains. This presentation is intended to provide an orientation to the Oncology Domains package that will facilitate a more focused review.

4. The Documentation Package Package location: http://gforge.nci.nih.gov/projects/sdsoncology/

5. The Documentation Package Navigate the folder tree down to the SDS Team Review Folder:

6. The Documentation Package The Review package contents: Tumor Domain Specifications –TU_TR_RS 2009-09-11.doc –Contains the SDTM specification for each of the proposed domains Tumor Domain Examples –Tumor Domain Examples 2009-09-13.xls –The spreadsheet contains brief data examples for each domain Oncology_CT –Oncology_CT__2009-09-10_DRAFT.xls –Controlled Terminology will be developed for these domains this spreadsheet contains a preliminary set of values SDS_Review_Comments –SDS_Review_Comments.xls –Spreadsheet for recording comments. Please return all comment spreadsheets to barrien@amgen.com.barrien@amgen.com –All comments will be discussed and dispositioned by the CDISC SDS Onc SIG and documentation will be updated accordingly.

7. The Development Team The development of oncology specific SDTM domains been ongoing for a number of years. This is a CDISC SDS sub-team effort with participation from additional Subject Matter Experts. During the development of the domains input has been provided by: –CDSIC SDS team members with an interest in Oncology –CDISC ADaM team members –Sponsor company Oncologists –Oncology Imaging vendors –FDA representation –NCI representation The current SDTM specifications have recently been reviewed by the wider CDISC SDS team The final documentation will either be incorporated as an Appendix to the SDTM-IG or exist as standalone, implementation specific, documentation

8. Purpose & Rationale Intended to represent data collected in clinical trials where tumors are: –Identified –Repeatedly measured/assessed –Used in an evaluation of therapeutic response Developed primarily with RECIST Criteria in mind and therefore data collected in solid tumor studies. –However, the domains should be appropriate for use in the assessment of other types of cancer such as lymphomas or gliomas Three Domains (TU / TR / RS) have been developed to provide a standardized representation to: –Reduce data redundancy –Provide a relational approach aligned with current SDS philosophy

9. TU : Tumor Identification Data that uniquely identifies a tumor. –Identified by an investigator and/or independent assessor In RECIST terms this equates to the identification of: –Target –Non-Target –New tumors A record in the TU domain contains the following information: –Unique tumor ID value; –Anatomical location of the tumor; –Method used to identify the tumor; –Role of the individual identifying the tumor; –Timing information.

10. TR : Tumor Results Represents quantitative measurements and/or qualitative assessments of the tumors identified in the TU domain. –Measurements are usually taken at baseline and then at each subsequent assessment (or visit) to support response evaluations. A record in the TR domain contains the following information: –unique tumor ID value; –Testcd/Test –Result –Method used –Role of the individual assessing the tumor –Timing information. The TR domain does not include anatomical location information on each measurement record because this would be a duplication of information already represented in TU. –This was a deciding factor in the multi-domain approach

11. RS : Response The RS domain represents the response evaluation determined from the data in TR. Data from other sources (other SDTM domains) might also be used in an assessment of response. For example: –MacDonald Response Criteria includes a neurological aspect. Should the Response Criteria used in the clinical trial be represented in the TS domain? –Rationale: the Response Criteria is really Study level metadata data and all subjects would be assessed using the same criteria. –Representing the criteria used on each record within the Responses domain would seem a little redundant. –A standardized TSPARM/TSVAL would be needed

12. Solicited Feedback 1.Should the proposed new SDTM variables be added to the SDTM model? –Do they add value and might they be have use in other domains? 2.Extend CT for the ND to include NOT APPLICABLE, etc. 3.Standardized SuppQual vars are proposed for more detailed anatomical location information – do these make sense? 4.Is “BONE SCAN” a commonly seen METHOD?

13. Solicited Feedback (contd.) 5.RECIST criteria calls for a value of 5mm to be recorded when a tumor is too small to measure. How should this standardization be represented in the TR domain? –Two methods for representing this can be found in the Domain Examples spreadsheet: Row 54 provides the information on a single row and uses the ORRES & STRESC/STRESN variables to provide the standardization. Rows 55 & 56 provide a 2 row approach to representing this information. Which method is preferred? The single row option is preferred by the Onc sub team 6.Should the Response Criteria used in the clinical trial be represented in the TS domain? –Response Criteria is really Study level metadata data - all subjects would be assessed using the same criteria. –Representing the criteria used on each record within the RS domain would seem redundant.

14. Review Comments Please provide all comments, including responses to solicited feedback, in the SDS_Review_Comments.xls spreadsheet provided in the review package. Please return all comment spreadsheets to barrien@amgen.com.barrien@amgen.com Agree on a deadline for providing feedback

15. Next Steps Feedback/Comment discussion: Follow-up Meeting? or Inclusion of FDA representatives in Onc Sub-team comments disposition discussions? Longer Term FDA Involvement in ongoing CDISC SDS Onc sub-team?