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

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 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

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 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

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? 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

Timing of IG Release ADaM IG, May 2008

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

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? ADaM IG, May 2008