adam ig, may 2008 adam implementation guide: its almost here. are you ready? sandra minjoe principal...
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ADaM IG, May 2008
ADaM Implementation Guide: It’s Almost Here. Are You Ready?
Sandra MinjoePrincipal Statistical Programmer AnalystGenentech, Inc
ADaM IG, May 2008
Outline
Purposes for Analysis Datasets and ADaM
Major Sections of ADaM IG Basic ADaM structure ADSL
Timing of IG Release
ADaM IG, May 2008
Purposes for Analysis Datasets and ADaM
ADaM IG, May 2008
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
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
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
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
Major Sections of ADaM IG
ADaM IG, May 2008
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
Basic ADaM Structure
A vertical structure 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
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
ADSL
Subject Level Analysis Data Required if any ADaM data is
submitted
ADaM IG, May 2008
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
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
What goes into ADSL
Required 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
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
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
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
Population Indicators:Conversions between SDTM & ADaM
* Include only population flag(s) needed for analysis
SDTM QNAMDescription
ADSL indicator variables*
FULLSET Full analysis flag FASFL, FASFN
ITTIntent-to-treat population flag
ITTFL, ITTFN
PPROTPer-protocol population flag
PPROTFL, PPORTFN
SAFETYSafety population flag
SAFFL, SAFFN
ADaM IG, May 2008
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
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
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
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
After Derivations
How much SDTM to keep in AD? 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
Timing of IG Release
ADaM IG, May 2008
Timing of IG Release
Jan 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
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
IG Review
ADaM IG, May 2008
Summary
Purposes for Analysis Datasets/ADaM
Major Sections of ADaM IG Basic ADaM structure ADSL
Timing of IG Release
Questions?