This document discusses ADaM metadata, which provides information about Analysis Data Model (ADaM) datasets. It presents examples of metadata for time to event analyses, including analysis dataset, variable, parameter value-level, and results metadata. The goal of metadata is to specify how to create ADaM and TFL datasets, define information for sponsors, and promote consistency between sites. Benefits include reduced communication needs, easier estimation and planning, and help for inexperienced users. Challenges include initial time/resource investment and determining who maintains the metadata.

1. Metadata and ADaM
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2. Disclaimer
Any views or opinions presented in this
presentation are solely those of the author and
do not necessarily represent those of the
company.
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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3. Agenda
•
Introduction of ADaM Metadata
•
Clincial Trial Process
•
Examples of how to create Metadata
•
Goal of ADaM Metadata
•
Pros and Cons
•
Conclusion
•
Questions & Answers
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4. ADaM Metadata
• Definition – Information of ADaM(Analysis Data
Model) datasets
• Types
–
–
–
–
Analysis Dataset Metadata
Analysis Variable Metadata
Analysis Parameter Value-Level Metadata
Analysis Results Metadata
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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5. Normal Clinical Trial Process
Protocol
SAP
Mock Up
Tables
CRF
DMDB
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Raw
Derived
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TFL
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6. CDISC Clinical Trial Process
Protocol
SAP
Mock Up
Tables
ADaM
Metadata
eCRF
EDC
SDTM
ADaM
TFL
ADaM Related Process
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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7. ADaM Related Process
ADaM Metadata
Analysis
Dataset
Metadata
Analysis
Variable
Metadata
Analysis
Parameter
value-level
Metadata
ADaM
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Analysis
Results
Metadata
TFL
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8. Example 1 - Time to Event Mock Up
table
Table 14.2.1
Time to Death by Treatment
PARAM = „Days to Death‟, TRTP
Analysis Population: Intent to Treat
ITTFL=„Y‟
Drug 1
Drug 2
p-value
__________________________________________________________________________________________
N
xxx
xxx
Median
xx
xx
x.xx
Q1, Q3
xx, xx
xx, xx
__________________________________________________________________________________________
AVAL(Days to Event), CNSR(Censor information)
proc lifetest data=ADTTEOS;
where PARAM=“Days to Death” and ITTFL=“Y”;
time AVAL*CNSR(1);
strata TRTP;
run;
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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9. Time to Event Analysis Dataset
Metadata
Dataset
Dataset
Dataset
Name Description Location
ADTTEOS Overall
Survival
Analysis
Dataset
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Dataset
Structure
Key
Class of Documentation
Variables Dataset
of Dataset
adtteos.xpt One record STUDYID, BDS
per subject USUBJID,
PARAM
per
parameter
©2012 Cytel Statistical Software & Services Pvt. Ltd.
adtteos.txt
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10. [CB1]Note
to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S
Example 1 : Time to Event Analysis
Variable Metadata including Analysis
Parameter Value-Level Metadata (1)
Dataset Parameter Variable Variable Label Variable Display
Name Identifier Name
Type
Format
Codelist /
Controlled
Terms
Source / Derivation
ADTTEOS *ALL*
STUDYID Study Identifier
text
$20
ADSL.STUDYID
ADTTEOS *ALL*
USUBJID Unique Subject
Identifier
text
$20
ADSL.USUBJID
ADTTEOS *ALL*
ITTFL
Intent-To-Treat
Population Flag
text
$1
Y, null
ADSL.ITTFL
ADTTEOS *ALL*
TRTP
Planned
Treatment
text
$40
Drug 1, Drug 2
ADSL.TRT01P
ADTTEOS *ALL*
TRTPN
Planned
Treatment (N)
integer
1.0
1 = Drug 1,
2 = Drug 2
ADSL.TRT01PN
ADTTEOS PARAMCD
PARAM
Parameter
text
$50
Days to Death
ADTTEOS *ALL*
PARAMCD Parameter Code text
$8
DEATH
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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11. [CB1]Note
to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S
Example 1 : Time to Event Analysis
Variable Metadata including Analysis
Parameter Value-Level Metadata (2)
Dataset Parameter Variable
Name Identifier
Name
Variable
Label
Variable Display
Type Format
Codelist /
Controlled Terms
Source / Derivation
ADTTEOS *ALL*
AVAL
Analysis Value float
8.2
ADT – STARTDT + 1
ADTTEOS *ALL*
STARTDT
YYYYMM
DD10.
ADSL.RANDDT
ADTTEOS *ALL*
ADT
Time to Event integer
Origin Date for
Subject
Analysis Date integer
YYYYMM
DD10.
SAS Date of DS.DSDTC
ADTTEOS *ALL*
CNSR
Censor
integer
1.0
ADTTEOS *ALL*
EVNTDESC Event or
Censoring
Description
text
$40
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0 for DS.DSDECOD =
„DEATH‟, 1 for any other
study completion
DEATH, COMPLETED DS.DSDECOD
THE STUDY, LOST TO
FOLLOW-UP, AE, PD
0, 1
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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12. [CB1]Note
to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S
Example 1 : Time to Event ADaM Dataset
USUBJID
TRTP
PARAM
AVAL
STARTDT
001-01-001 Study Drug 1
Days to
Death
157
001-01-002 Study Drug 2
Days to
Death
001-01-003 Study Drug 2
001-01-004 Study Drug 1
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ADT
CNSR
EVNTDESC
2011-01-04 2011-06-10
1
COMPLETED
THE STUDY
116
2011-02-01 2011-05-28
1
AE
Days to
Death
88
2011-02-05 2011-05-04
0
DEATH
Days to
Death
102
2011-03-20 2011-06-30
1
PD
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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13. Example 1 : Time to Event Analysis
Results Metadata
Metadata Field
Metadata
DISPLAY
IDENTIFIER
DISPLAY NAME
Table 14.2.1
RESULT
IDENTIFIER
PARAM
Days to Death
PARAMCD
DEATH
ANALYSIS
VARIABLE
REASON
AVAL
DATASET
ADTTEOS
Time to Death by Treatment, Analysis Population: Intent to Treat
Days to Death
Primary efficacy analysis
ITTFL=“Y” and PARAM = „Days to Death‟
SELECTION
CRITERIA
DOCUMENTATION See SAP Section XX for details. Program: t-14-012-001-death.txt
PROGRAMMING
STATEMENTS
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proc lifetest data= ADTTEOS;
where ITTFL=„Y‟ and PARAM = “Days to Death”;
time AVAL*CNSR(1);
strata TRTP;
run;
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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14. Example 2 : Time to Event Mock Up
table
Table 14.2.2
Time to Progression Free Survival : Cox Proportional Hazard Model
PARAM = ‘Days to Progression Free Survival’, TRTP
Analysis Population: Intent to Treat
ITTFL=„Y‟
Drug 1
Drug 2
p-value
__________________________________________________________________________________________
N
xxx
xxx
Median
xx
xx
x.xx
Q1, Q3
xx, xx
xx, xx
__________________________________________________________________________________________
AVAL(Days to Event), CNSR(Censor information)
proc phreg data=ADTTEOS;
where PARAM=“Days to Progression Free Survival” and ITTFL=“Y”;
model AVAL*CNSR(1) = TRTP AGE SEX ;
run;
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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15. [CB1]Note
to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S
Example 2 : Time to Event Analysis
Variable Metadata including Analysis
Parameter Value-Level Metadata (1)
Dataset Parameter Variable Variable Label Variable Display
Name Identifier Name
Type
Format
Source / Derivation
Codelist /
Controlled Terms
ADTTEOS *ALL*
STUDYID Study Identifier
text
$20
ADSL.STUDYID
ADTTEOS *ALL*
USUBJID Unique Subject
Identifier
text
$20
ADSL.USUBJID
ADTTEOS *ALL*
ADTTEOS *ALL*
ADTTEOS *ALL*
AGE
SEX
ITTFL
Age
Sex
Intent-To-Treat
Population Flag
integer
text
text
3.0
$1
$1
Y, null
ADSL.AGE
ADSL.SEX
ADSL.ITTFL
ADTTEOS *ALL*
TRTP
Planned
Treatment
text
$40
Drug 1, Drug 2
ADSL.TRT01P
ADTTEOS *ALL*
TRTPN
Planned
Treatment (N)
integer
1.0
1 = Drug 1,
2 = Drug 2
ADSL.TRT01PN
ADTTEOS PARAMCD
PARAM
Parameter
text
$50
ADTTEOS *ALL*
PARAMCD Parameter Code text
Days to Death
Days to Progression
Free Survival
DEATH
PFS
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$8
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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16. Example 2 : Time to Event Analysis
Variable Metadata including Analysis
Parameter Value-Level Metadata (2)
Dataset Parameter Variable
Name Identifier
Name
Variable
Label
Variable Display
Type Format
Codelist /
Controlled Terms
Source / Derivation
ADTTEOS *ALL*
AVAL
Analysis Value float
8.2
ADT – STARTDT + 1
ADTTEOS *ALL*
STARTDT
YYYYMM
DD10.
ADSL.RANDDT
ADTTEOS *ALL*
ADT
Time to Event integer
Origin Date for
Subject
Analysis Date integer
YYYYMM
DD10.
SAS Date of DS.DSDTC
ADTTEOS DEATH
CNSR
Censor
integer
1.0
ADTTEOS PFS
CNSR
Censor
integer
1.0
ADTTEOS *ALL*
EVNTDESC Event or
Censoring
Description
text
$40
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0 for DS.DSDECOD =
„DEATH‟, 1 for any other
study completion
0, 1
0 for DS.DSDECOD
in(„DEATH‟ , „PD‟), 1 for any
other study completion
DEATH, COMPLETED DS.DSDECOD
THE STUDY, LOST TO
FOLLOW-UP, AE, PD
0, 1
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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17. [CB1]Note
to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S
Example 2 : Time to Event ADaM Dataset
USUBJ AGE SEX TRTP
ID
PARAM
AVA STAR
L
TDT
ADT
CNSR
EVNTDESC
001-01001
43
M
Study
Drug 1
Days to Death
157
201101-04
201106-10
1
COMPLETED
THE STUDY
001-01002
57
F
Study
Drug 2
Days to Death
116
201102-01
201105-28
1
AE
001-01003
71
M
Study
Drug 2
Days to Death
88
201102-05
201105-04
0
DEATH
001-01004
55
F
Study
Drug 1
Days to Death
102
201103-20
201106-30
1
PD
001-01001
43
M
Study
Drug 1
Days to Progression 157
Free Survival
201101-04
201106-10
1
COMPLETED
THE STUDY
001-01002
57
F
Study
Drug 2
Days to Progression 116
Free Survival
201102-01
201105-28
1
AE
001-01003
71
M
Study
Drug 2
Days to Progression 88
Free Survival
201102-05
201105-04
0
DEATH
001-01004
55
F
Study
Drug 1
Days to Progression 102
Free Survival
201103-20
201106-30
0
PD
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18. Example 2 : Time to Event Analysis
Results Metadata
Metadata Field
Metadata
DISPLAY
IDENTIFIER
DISPLAY NAME
Table 14.2.2
RESULT
IDENTIFIER
PARAM
Days to Progression Free Survival
PARAMCD
PFS
ANALYSIS
VARIABLE
REASON
AVAL
DATASET
ADTTEOS
Time to Progression Free Survival : Cox Proportional Hazard Model
Days to Progression Free Survival
Secondary efficacy analysis
ITTFL=“Y” and PARAM=“Days to Progression Free Survival‟
SELECTION
CRITERIA
DOCUMENTATION See SAP Section XX for details. Program: t-14-002-002-pfs.txt
PROGRAMMING
STATEMENTS
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proc phreg data= ADTTEOS;
where ITTFL=„Y‟ and PARAM = “Days to Progression Free Survival’;
model AVAL*CNSR(1) = TRTP AGE SEX;
run;
©2012 Cytel Statistical Software & Services Pvt. Ltd.
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19. Summary of Examples
Mock Up Tables
ADaM Metadata
14.2.1
14.2.2
Dataset
ADTTEOS
Variables
STUDYDI, USUBJID
ITTFL
TRTP, TRTPN
PARAM, PARAMCD
AVAL
STARTDT, ADT
CNSR
EVNTDESC
AGE
SEX
Parameter DEATH
Results Days to Death
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
PFS
Days to Progression
Free Survival
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20. Goal of Metadata
• Serve as Spec and Define
– Spec : provide the programmers how ADaM and some TFL
can be created
– Define : datasets information for sponsors
• Central document for all programmers and statisticians
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21. Goal of Metadata (2)
• Minimize the communication traffic in virtual office
setting
–
–
–
–
Philadelphia Office
Boston Office
India Office
Remote Programming
• Reconciliation between ADaM datasets and Metadata
– use macros to check wether ADaM datasets follow
ADaM Metadata.
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22. Cons
• Who will prepare and maintain the metadata
• CDISC expert(SDTM, ADaM and so on)
• Programmer Lead
• Statistician
• The initial investment on resource and time at
the early stage of the study
• Two many metadata?
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©2012 Cytel Statistical Software & Services Pvt. Ltd.
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23. Pros (1)
• Consistency in ADaM datasets
–
–
–
–
Label
Name
Format
# of variables
• Help the inexperience personnel – ADaM is new
• The central document between developers and
validators – especially for the virtual office setting
• Helps the programmers on efficacy analysis.
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24. Pros (2)
• Better estimate on the number of ADaM datasets –
help the planning and resourcing.
• Review on Mock Up tables and SAP
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25. Conclusion
• The concept of Metadata is “Plan your work and work
your plan”
• ADaM Metadata is ongoing until all are done.
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26. Questions?
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