1. Quick tour of CDISC’s ADaM standard

2. FDA/PHuSE ADaM Kick off Meeting

3. Location in the CDISC Standards
ADaM is the last standard in the food chain when it comes to presenting the results of a clinical trial for revision by the authorities.

4. Clinical trial data and information flow
Going back to basics, a protocol is written with the plans for the trial and from that some sort of Statistical Analysis Plan is written to define how the results from the patients will be presented in order to prove safety and efficacy of the drug. Data is collected from the patients and stored in a system called SDTM. The SDTM data is taken and processed into other datasets called Analysis Datasets which summarise and calculate results. These Analysis datasets are then used to create reports here called Analysis results.

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
SDTM
ADaM
TLGs
process
Analysis Datasets sometimes called VADs Value Added Datasets

6. Differences between SDTM and 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
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

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
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
Analysis Data Model v
Basic principles and standards for metadata to apply to all analysis datasets
Introduction to the Basic Data Structure (BDS) and Subject Level analysis dataset (ADSL)
Descriptive metadata (specs) examples
Analysis Data Model Implementation Guide v
Definition and standards for Basic Data Structure (BDS) and Subject Level Analysis dataset (ADSL)
Standard implementation of analysis issues
Standard variable names and labels
ADaM Examples Document 2011
Illustrates ADaM concepts and principles
It does NOT implement or advocate new rules or standards
Analysis Data Model Data Structure for Adverse Event Analysis v1.0
2012 Dataset structure specifically for AE data
The ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.0
2012 How to use the BDS for TTE data
ADaM Validation Checks v
ADaM Validation Checks in pdf and excel format

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 Metadata Analysis 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 Metadata Analysis Dataset Metadata

17. ADaM Metadata Analysis Variable Metadata
Variable Name and Dataset Name
Label
Type
Codelist /Controlled terminology
Source or derivation
Core (Req Cond Perm)
CDISC Notes
Analysis variable metadata describes each variable in the dataset.

18. ADaM Metadata Analysis Variable Metadata

19. ADaM Metadata Analysis 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.
In a BDS analysis dataset, the variable PARAM contains a unique description for every analysis parameter included in that dataset. The variable PARAMCD contains the short name of the analysis parameter in PARAM, with a one-to-one mapping between the two variables.

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 Metadata Analysis 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.
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.
For further details see ADaM 2.1 Section 5.3 “ Analysis Results Metadata”

23. ADaM Metadata Analysis 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