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
 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

ADSL indicator
SDTM QNAM
Description variables*
FULLSET Full analysis flag FASFL, FASFN
Intent-to-treat
ITT ITTFL, ITTFN
population flag
Per-protocol PPROTFL,
PPROT
population flag PPORTFN
Safety population
SAFETY SAFFL, SAFFN
flag

* 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?

 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?

ADaM IG, May 2008