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.

Outline Background ADaM Setup Steps for Lipid ADaM data Summary

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 http://www.cdisc.org/adam

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

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)

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

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

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

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

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 2008-09-15 -16 1002 2.8 DAY 1 2 2008-10-01 1003 2.73 DAY 15 3 2008-10-15 15 1004 2.68 1005 2.74 DAY 28 4 2008-10-28 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

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

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

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

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

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;

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