1. ADaM Implementation Guide: It’s Almost Here. Are You Ready?
Sandra Minjoe
Principal Statistical Programmer Analyst
Genentech, Inc
ADaM IG, May 2008

2. Outline Purposes for Analysis Datasets and ADaM
Major Sections of ADaM IG
Basic ADaM structure
ADSL
Timing of IG Release
ADaM IG, May 2008

3. Purposes for Analysis Datasets and ADaM
ADaM IG, May 2008

4. Purposes for Analysis Datasets
Combine data needed for specific analysis(es)
Imputed data
Target windows
Selection Flags
Allow “One Proc Away” Analysis
Generated with minimal programming
Allow alternate analysis(es) and exploration
ADaM IG, May 2008

5. Other Needs for Analysis Datasets
Provide information
How to appropriately use data
How to replicate results and explore alternate analyses
Convey traceability
How variables and observations were derived
ADaM IG, May 2008

6. Purposes of ADaM Combine data across domains Provide derived data
Variables and observations used for statistical analyses
Provide metadata
Explain the analysis and results
Provide traceability
Back to collected data
ADaM IG, May 2008

7. ADaM and Reviewers ADaM helps the reviewer trace:
What you said you would do
What you did
Why they are different
Traceability is important
Does NOT replace communication with FDA
ADaM IG, May 2008

8. Major Sections of ADaM IG
ADaM IG, May 2008

9. Major Sections of ADaM IG
ADaM Data Structure
Standard ADaM Metadata
Categories of variables
ADSL
Implementation Issues & Solutions
Columns vs. Rows
Examples
ADaM IG, May 2008

10. Basic ADaM Structure A vertical structure Includes observations for
One record per subject per analysis parameter per analysis time point
Includes observations for
Observed values
Derived values required for analysis
Value-level metadata is needed
Allows flexibility
Predictable structure
ADaM IG, May 2008

11. Categories of Variables
Subject Identifiers
SDTM Identifiers
ADaM Timing Identifiers (e.g. AVISIT)
ADaM Parameter Identifiers (e.g. PARAM)
ADaM Analysis Values (e.g. AVAL)
Analysis Enabling Variables (e.g. ANLFL, TRTP)
Supportive Variables (e.g. --SEQ)
ADaM IG, May 2008

12. ADSL Subject Level Analysis Data
Required if any ADaM data is submitted
ADaM IG, May 2008

13. ADSL Content Contains basic subject information
Demographic, baseline, disposition data
Used as source for these variables in other analysis datasets
Has standard names and attributes
Tools can be built to use it
Use it for Baseline and Disposition table programming
ADaM IG, May 2008

14. ADSL Structure Structure: 1 record per subject
Regardless of trial design
Allows simple merging with any other dataset
Even SDTM
Use it for population denominators
ADaM IG, May 2008

15. What goes into ADSL Required variables Permissible variables
Study identifiers
Subject demographics
Population indicator(s)
Treatment variables
Trial dates
Permissible variables
Numeric equivalents of flags
Stratification variables
Treatment duration and compliance variables
Other key visit dates and durations
Protocol specific event information, such as death/survival
ADaM IG, May 2008

16. Required ADSL Category: Study Identifiers
Required variables: Likely from the SDTM DM domain
STUDYID
USUBJID
SITEID
Optional study-specific identifiers, e.g:
SITEGRP (pooled group of sites used for analysis)
ADaM IG, May 2008

17. Required ADSL Category: Subject Demographics
Required variables: Likely from the SDTM DM domain
AGE
SEX
RACE
Optional study-specific identifiers, e.g.:
AGEGRP (age group)
RACEGRP (race group)
ADaM IG, May 2008

18. Required ADSL Category: Population Indicator(s)
Required variables:
At least one flag
Flag for each population defined in SAP
Character flag is required
Numeric flags can be included
Some common example flags:
FASFL (full analysis set)
ITTFL (intent-to-treat population)
PPROTFL (per-protocol population)
SAFFL (safety population)
ADaM IG, May 2008

19. Population Indicators: Conversions between SDTM & ADaM
SDTM QNAM
Description
ADSL indicator variables*
FULLSET
Full analysis flag
FASFL, FASFN
ITT
Intent-to-treat population flag
ITTFL, ITTFN
PPROT
Per-protocol population flag
PPROTFL, PPORTFN
SAFETY
Safety population flag
SAFFL, SAFFN
* Include only population flag(s) needed for analysis
ADaM IG, May 2008

20. Required ADSL Category: Treatment Variables
Required variables:
ARM (planned arm)
TRTP (planned treatment)
Optional study-specific variables, e.g.:
TRTA (actual treatment)
Use when subject received something other than planned treatment
TRTxA and TRTxP
Used instead of TRTA and TRTP
For when multiple treatment regimens are assigned, e.g., cross-over design
ADaM IG, May 2008

21. Required ADSL Category: Trial Dates
Required SDTM variables
RFSTDTC and RFENDTC
Retained for reference, traceability
Required numeric dates
RANDDT (if trial is randomized)
TRTSTDT (Date of 1st treatment start)
TRTENDT (Date of last treatment end)
Format to be human-readable
If appropriate, instead use
TRTxSTDT and TRTxENDT
Date-time if appropriate
ADaM IG, May 2008

22. Implementation Issues & Solutions
Building Analysis Datasets
Step 1: bring in data from elsewhere
Step 2: derive new data
Columns
Rows
Step 3: clean up
ADaM IG, May 2008

23. Rules for Rows vs. Columns
Add column if all data needed for derivation is in the row
Change from baseline
Add row if need more than one row to derive new information
LOCF, Average across a visit, AUC
Add row for transformations that go across all analysis variables
Log10
ADaM IG, May 2008

24. After Derivations How much SDTM to keep in AD? Consider keeping if:
Data used to derive analysis variables but otherwise not needed for analysis
Consider keeping if:
Helps with traceability
Easy to subset to get analysis records
“Extra” data will allow for derivation of alternate analyses
Keep audience in mind
ADaM IG, May 2008

25. Timing of IG Release
ADaM IG, May 2008

26. Timing of IG Release Jan 30, 2008 March – May, 2008 May 30, 2008
Released for internal CDISC review
March – May, 2008
ADaM making doc modifications
May 30, 2008
Planned date for public review release
Late August, 2008
Approximate review due date
ADaM IG, May 2008

27. IG Review Review process will be similar to other CDISC reviews
Spreadsheet to collect comments
Review can be done by:
Company
Individual
Other?
ADaM IG, May 2008

28. IG Review
ADaM IG, May 2008

29. Summary Purposes for Analysis Datasets/ADaM Major Sections of ADaM IG
Basic ADaM structure
ADSL
Timing of IG Release
Questions?
ADaM IG, May 2008