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

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?