Quick tour of CDISC’s ADaM standard

1. Quick tour of CDISC’s ADaM standard

2. FDA/PHuSEADaM Kick off Meeting

3. Location in the CDISC Standards

4. Clinical trial data and information flow

5. Analysis Datasets and Tables, Listings, Graphs (TLGs) VAD Module Reporting module In: SDTMv data sets Out: Analysis data In: Analysis data sets Out: Standard TLGs process process TLGs SDTM ADaM Analysis Datasets sometimes called VADs Value Added Datasets

6. SDTM Designed to store trial data as collected No redundancy Designed for data transfer and Interoperability Few derived variables Standard domains for each type of subject area Predominantly character variables Dates are ISO8601 character strings ADaM Designed for communication of scientific results of the trial Contains collected and derived data as per analysis plan May use variables from multiple SDTM domains and other ADaM datasets Redundancy is needed for easy analysis and may contain variables for supportive purposes Numeric variables are often needed for analysis Dates are numeric to allow calculation Heavily reliant on descriptive metadata Differences between SDTM and ADaM

7. Going from SDTM to ADaM example of “composite endpoint”

8. ADaM is designed to standardise the way that analysis results are stored and thus presented to authorities.It is predominantly designed for statistical analyses to reduce and eliminate any processing required by the reviewer.

9. Where is it described:Core ADaM Standard Documents www.cdisc.org/adam Analysis Data Model v2.1 Analysis Data Model Implementation Guide v1.0 Analysis Data Model Data Structure for Adverse Event Analysis v1.0 The ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.0 ADaM Examples Final ADaM Validation Checks v1.2 ……..Plus Appendix references

10. ADaM Dataset Classes • ADSL (Subject Level Analysis Data) • one record per subject • the only required dataset in a CDISC-based submission • allows simple merging with other datasets • BDS (Basic Data Structure) – one or more records per subject, per analysis parameter per analysis timepoint(Also used for time to event analyses and LABs. • ADAE(Adverse Events) one row per subject per adverse event recorded • Other future planned additional datasets : eg General Occurrences: Medications, Medical History.

11. ADSL & BDS • Go to implementation guide for list of variables.

12. BDS example

13. ADaM RA VAD

14. ADaM “Metadata” as described in the docs is: Analysis Dataset Metadata – description of dataset Analysis Variable Metadata (dataset structures) Analysis Parameter Value-Level Metadata – specs/derivations used to create analysis values (paramcds) Analysis Results Metadata – derivations and statistical procedures used for a report.

15. ADaM MetadataAnalysis Dataset Metadata • Dataset name (e.g. ADEFF) • Dataset Description (e.g. Primary Efficacy analysis dataset) • Location – filepath where the dataset is stored • Structure (e.g. one observation per subject per visit) • Class (e.g. “ADSL” , “BDS” or OTHER) • Key variables (e.g. USUBJID, AVISIT, PARAMCD) • Documentation (e.g. Descriptions of source data, processing steps or references to external documents like Protocol, DAP) • These can be included as separate files and hyperlinked

16. ADaM MetadataAnalysis Dataset Metadata

17. ADaM MetadataAnalysis Variable Metadata Variable Name and Dataset Name Label Type Codelist /Controlled terminology Source or derivation Core (Req Cond Perm) CDISC Notes

18. ADaM MetadataAnalysis Variable Metadata

19. ADaM MetadataAnalysis Parameter-Value Level Metadata Part of Analysis Variable Metadata for VADs with BDS structure Parameter Identifier for different values of PARAM/PARAMCD contains specifications for how the parameters are derived.

20. Example of metadata for param codes – value level metadata

21. Descriptive metadata representation… …………The display presentation of the metadata should be determined between the sponsor and the recipient. The example is only intended to illustrate content and not appearance.

22. ADaM MetadataAnalysis Results Metadata Allows reviewers to link from an analysis result to important information describing the analysis such as the reason for performing the analysis, and the dataset and selection criteria used to generate the analysis These metadata provide traceability from a result used in a statistical display to the data in the analysis datasets. Analysis results metadata are not required. However, best practice is that they be provided to assist the reviewer by identifying the critical analyses, providing links between results, documentation, and datasets, and documenting the analyses performed.

23. ADaM MetadataAnalysis Results Metadata

24. Validation Checks

25. Special AE dataset structure

26. Summary of ADaM contents ADSL dataset structure BDS dataset structure (with BDS TTE and Lab section) ADAE dataset structure Descriptive metadata – for datasets, parameters (value level metadata) and results (Table, Listings, Graphs (TLG)) metadata. Validation checks Do we have to bear in mind direct links between SDTM model and ADaM model (eg ADSL, ADAE) ………………scoping discussion