1. A Taste of ADaM Presented by: Peng/Zik Liu MSD (Shanghai) Pharma Co.
Beilei Xu Accenture
Changhong Shi Merck Sharp & Dohme Corp.
Presented by: Peng/Zik Liu
MSD (Shanghai) Pharma Co.

2. Outline
Background
ADaM
Setup Steps for Lipid ADaM data
Summary

3. Background CDISC - Clinical Data Interchange Standards Consortium
SDTM - Study Data Tabulation Model
Standard for interchange of collected data
ADaM - Analysis Data Model
Standard for analysis data

4. ADaM Standard Data Structure
ADSL: Subject level analysis data
one record per subject
subject-level population flags, planned and actual treatment variables, demographic information, randomization factors, sub-grouping variables, and important dates
BDS: Basic Data Structure
Long and skinny structure: contains one or more records per subject, per analysis parameter, and per analysis time point
“One-proc” away readiness for analysis
Traceability

5. BDS Variables A central set of variables: Other variables:
The analysis parameter: e.g., PARAM
The value being analyzed: e.g., AVAL and AVALC
Other variables:
Provide more information about the value being analyzed (e.g., the subject identification)
Describe and trace the derivation of the variable (e.g., DTYPE)
Enable the analyses (e.g., treatment variables, covariates)

6. Implementation Consideration
Number of ADaM datasets needed
Derivation of analysis endpoints, analysis windows, analysis values, and imputation of missing values
Setup of analysis flags and population flags

7. Lipid Analysis Data - ADLP
Lipid endpoints:
LDL - C
HDL - C
LDL/HDL ratio
Analysis time points:
SCREENING
BASELINE
WEEK 2
WEEK 4
Analysis population- Full Analysis Set

8. Lipid Analysis Data - ADLP
Subject identifiers: STUDYID, USUBJID, SUBJID, and SITEID
Treatment variables: TRTP, TRPA, TRTPN, and TRTAN
Analysis parameter variables: PARAM, PARAMCD, PARAMN, and PARAMTYP
Analysis timing variables: ADT and ADY
The analysis value variables: AVAL, BASE, and CHG
The analysis flag variable - ANL01FL
The parameter population flag - FASPFL
The traceability variables: SRCDOM, SRCVAR, and SRCSEQ

9. ADLP Setup Steps Obtain Variables from Source SDTM LB Domain
Derive New Analysis Endpoints (PARAMTYP)
Handle Negatives (or under detection) and Multiple Records on the Same Date (DTYPE)
Set Analysis Flag Variables (ANLzzFL)
Compute Change, Percent Change from Baseline (BASE, CHG, PCHG)
Set Population Flag Variables

10. Obtain Data from SDTM LB Domain
USUBJID
LBSEQ
LBTESTCD
LBTEST
LBSTRESN
LBSTRESU
VISIT
VISITNUM
LBDTC
LBDY
1A-4_02
1001
LDL
LDL Cholesterol
2.36
mmol/L
SCRNING 1
-16
1002
2.8
DAY 1 2
1003
2.73
DAY 15 3 15
1004
2.68
1005
2.74
DAY 28 4 28
ADLP:
USUBJID
PARAM
AWRANGE
AVISIT
AVISITN
ADT
ADY
AVAL
SRCDOM
SRCVAR
SRCSEQ
1A-4_02
LDL-C (mmol/L)
< Day 1
SCREENING
-99
9/15/2008
-16
2.36 LB
LBSTRESN
1001
Day 1
Baseline
10/1/2008 1
2.8
1002
2-21 Days
Week 2 2
10/15/2008 15
2.73
1003
2.68
1004
>= 22 Days
Week 4 4
10/28/2008 28
2.74
1005 10

11. Derive New Analysis Endpoint LDL/HDL Ratio
ADLP:
USUBJID
PARAM
AWRANGE
AVISIT
AVISITN
ADT
ADY
AVAL
PARAMTYP
1A-4_02
LDL/HDL ratio
< Day 1
SCREENING
-99
9/15/2008
-16
2.226
DERIVED
Day 1
Baseline
10/1/2008 1
2.593
2-21 Days
Week 2 2
10/15/2008 15
2.438
2.459
>= 22 Days
Week 4 4
10/28/2008 28
2.383 11

12. Handle Multiple Records on the Same Date
USUBJID
PARAM
AWRANGE
AVISIT
AVISITN
ADT
AVAL
SRCDOM
SRCVAR
SRCSEQ
DTYPE
1A-4_02
LDL-C (mmol/L)
< Day 1
SCREENING
-99
9/15/2008
2.36 LB
LBSTRESN
1001
Day 1
Baseline
10/1/2008
2.8
1002
2-21 Days
Week 2 2
10/15/2008
2.73
1003
2.68
1004
2.71
AVERAGE
>= 22 Days
Week 4 4
10/28/2008
2.74
1005 12

13. Set Analysis Flag Variables (ANLzzFL)
USUBJID
PARAM
AWRANGE
AVISIT
AVISITN
ADT
ADY
AVAL
DTYPE
ANL01FL
1A-4_02
LDL-C (mmol/L)
< Day 1
SCREENING
-99
9/15/2008
-16
2.36 Y
Day 1
Baseline
10/1/2008 1
2.8
2-21 Days
Week 2 2
10/15/2008 15
2.73
2.68
2.71
AVERAGE
>= 22 Days
Week 4 4
10/28/2008 28
2.74

14. Set Population Flag Variables
USUBJID
PARAM
AWRANGE
AVISIT
AVISITN
AVAL
BASE
CHG
DTYPE
ANL01FL
FASPFL
1A-4_02
LDL-C (mmol/L)
< Day 1
SCREENING
-99
2.36
2.8 Y
Day 1
Baseline
2-21 Days
Week 2 2
2.73
-0.07
2.68
-0.12
2.71
-0.09
AVERAGE
>= 22 Days
Week 4 4
2.74
-0.06

15. One-Proc Away proc mixed data=adlp;
where paramcd=‘LDL’ and anl01fl=‘Y’
and faspfl=‘Y’ and avisitn in (0,2,4);
class subjid avisit trta;
model chg=avisit trta trta*avisit;
repeated avisit/subject=subjid type=un;
run;

16. Summary The setup steps shown above enable:
the creation of the ADaM Basic Data Structure (BDS)
traceability between analysis data and source data
"one-proc" away readiness for analysis
Further development can be made to standardize the programs for analysis data setup