metadata and adam

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Metadata and ADaM

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www.cytel.com ©2012 Cytel Statistical Software & Services Pvt. Ltd.

Disclaimer

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Any views or opinions presented in this presentation are solely those of the author and do not necessarily represent those of the company.


Agenda

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• Introduction of ADaM Metadata

• Clincial Trial Process

• Examples of how to create Metadata

• Goal of ADaM Metadata

• Pros and Cons

• Conclusion

• Questions & Answers


ADaM Metadata

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• Definition – Information of ADaM(Analysis Data Model) datasets

• Types– Analysis Dataset Metadata– Analysis Variable Metadata – Analysis Parameter Value-Level Metadata– Analysis Results Metadata


Normal Clinical Trial Process

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Protocol SAP Mock Up Tables

CRF

DMDB Raw TFLDerived


CDISC Clinical Trial Process

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Protocol SAP Mock Up Tables

eCRF

EDC SDTM

ADaMMetadata

TFLADaM

ADaM Related Process


ADaM Related Process

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Analysis Dataset

Metadata

TFLADaM

Analysis Variable

Metadata

Analysis Parametervalue-levelMetadata

Analysis Results

Metadata

ADaM Metadata


Example 1 - Time to Event Mock Up table

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Table 14.2.1

Time to Death by Treatment

PARAM = ‘Days to Death’, TRTP

Analysis Population: Intent to Treat

ITTFL=‘Y’

Drug 1Drug 2 p-value

__________________________________________________________________________________________N xxx

xxxMedian xx

xx x.xxQ1, 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;


Time to Event Analysis Dataset Metadata

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Dataset Name

Dataset Description

Dataset Location

Dataset Structure

Key Variables of Dataset

Class of Dataset

Documentation

ADTTEOS Overall Survival Analysis Dataset

adtteos.xpt One record per subject per parameter

STUDYID, USUBJID, PARAM

BDS adtteos.txt


Example 1 : Time to Event Analysis Variable Metadata including Analysis Parameter Value-Level Metadata (1)

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[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 SAS use a file extension for ASCII text files other than .txt, the file name should include the native file extension generated by the analysis tool for ASCII text program files, e.g. mySAScode.sas.

Dataset Name

Parameter Identifier

Variable Name

Variable Label Variable Type

Display 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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Dataset Name


Variable Name

Variable Label

Variable Type

Display Format

Codelist / Controlled Terms

Source / Derivation

ADTTEOS *ALL* AVAL Analysis Value float 8.2 ADT – STARTDT + 1

ADTTEOS *ALL* STARTDT Time to Event Origin Date for Subject

integer YYYYMMDD10.

ADSL.RANDDT

ADTTEOS *ALL* ADT Analysis Date integer YYYYMMDD10.

SAS Date of DS.DSDTC

ADTTEOS *ALL* CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD = ‘DEATH’, 1 for any other study completion

ADTTEOS *ALL* EVNTDESC Event or Censoring Description

text $40 DEATH, COMPLETED THE STUDY, LOST TO FOLLOW-UP, AE, PD

DS.DSDECOD


Example 1 : Time to Event ADaM Dataset

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USUBJID TRTP PARAM AVAL STARTDT ADT CNSR EVNTDESC001-01-001 Study Drug 1 Days to

Death157 2011-01-04 2011-06-10 1 COMPLETED

THE STUDY

001-01-002 Study Drug 2 Days to Death

116 2011-02-01 2011-05-28 1 AE


88 2011-02-05 2011-05-04 0 DEATH


102 2011-03-20 2011-06-30 1 PD


Example 1 : Time to Event Analysis Results Metadata

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Metadata Field Metadata

DISPLAY IDENTIFIER

Table 14.2.1

DISPLAY NAME Time to Death by Treatment, Analysis Population: Intent to Treat

RESULT IDENTIFIER

Days to Death

PARAM Days to Death

PARAMCD DEATH

ANALYSIS VARIABLE

AVAL

REASON Primary efficacy analysis

DATASET ADTTEOS

SELECTION CRITERIA

ITTFL=“Y” and PARAM = ‘Days to Death’

DOCUMENTATION See SAP Section XX for details. Program: t-14-012-001-death.txt

PROGRAMMING STATEMENTS

proc lifetest data= ADTTEOS; where ITTFL=‘Y’ and PARAM = “Days to Death”; time AVAL*CNSR(1); strata TRTP;run;


Example 2 : Time to Event Mock Up table

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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 1Drug 2 p-value

__________________________________________________________________________________________N xxx

xxxMedian xx

xx x.xxQ1, 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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Dataset Name


Variable Name

Variable Label Variable Type

Display Format


Source / Derivation

ADTTEOS *ALL* STUDYID Study Identifier text $20 ADSL.STUDYID

ADTTEOS *ALL* USUBJID Unique Subject Identifier

text $20 ADSL.USUBJID

ADTTEOS *ALL* AGE Age integer 3.0 ADSL.AGEADTTEOS *ALL* SEX Sex text $1 ADSL.SEXADTTEOS *ALL* ITTFL Intent-To-Treat

Population Flagtext $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 DeathDays to Progression Free Survival

ADTTEOS *ALL* PARAMCD Parameter Code text $8 DEATHPFS



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Dataset Name


Variable Name

Variable Label

Variable Type

Display Format


Source / Derivation

ADTTEOS *ALL* AVAL Analysis Value float 8.2 ADT – STARTDT + 1

ADTTEOS *ALL* STARTDT Time to Event Origin Date for Subject

integer YYYYMMDD10.

ADSL.RANDDT

ADTTEOS *ALL* ADT Analysis Date integer YYYYMMDD10.

SAS Date of DS.DSDTC

ADTTEOS DEATH CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD = ‘DEATH’, 1 for any other study completion

ADTTEOS PFS CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD in(‘DEATH’ , ‘PD’), 1 for any other study completion

ADTTEOS *ALL* EVNTDESC Event or Censoring Description

text $40 DEATH, COMPLETED THE STUDY, LOST TO FOLLOW-UP, AE, PD

DS.DSDECOD


Example 2 : Time to Event ADaM Dataset

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USUBJID

AGE SEX TRTP PARAM AVAL

STARTDT

ADT CNSR EVNTDESC

001-01-001

43 M Study Drug 1

Days to Death 157 2011-01-04

2011-06-10

1 COMPLETED THE STUDY

001-01-002

57 F Study Drug 2

Days to Death 116 2011-02-01

2011-05-28

1 AE

001-01-003

71 M Study Drug 2

Days to Death 88 2011-02-05

2011-05-04

0 DEATH

001-01-004

55 F Study Drug 1

Days to Death 102 2011-03-20

2011-06-30

1 PD

001-01-001

43 M Study Drug 1

Days to Progression Free Survival

157 2011-01-04

2011-06-10

1 COMPLETED THE STUDY

001-01-002

57 F Study Drug 2


116 2011-02-01

2011-05-28

1 AE

001-01-003

71 M Study Drug 2


88 2011-02-05

2011-05-04

0 DEATH

001-01-004

55 F Study Drug 1


102 2011-03-20

2011-06-30

0 PD


Example 2 : Time to Event Analysis Results Metadata

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Metadata Field Metadata

DISPLAY IDENTIFIER

Table 14.2.2

DISPLAY NAME Time to Progression Free Survival : Cox Proportional Hazard Model

RESULT IDENTIFIER


PARAM Days to Progression Free Survival

PARAMCD PFS

ANALYSIS VARIABLE

AVAL

REASON Secondary efficacy analysis

DATASET ADTTEOS

SELECTION CRITERIA

ITTFL=“Y” and PARAM=“Days to Progression Free Survival’

DOCUMENTATION See SAP Section XX for details. Program: t-14-002-002-pfs.txt

PROGRAMMING STATEMENTS

proc phreg data= ADTTEOS; where ITTFL=‘Y’ and PARAM = “Days to Progression Free Survival’; model AVAL*CNSR(1) = TRTP AGE SEX;run;


Summary of Examples

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Mock Up Tables 14.2.1 14.2.2

ADaM Metadata Dataset ADTTEOS

Variables STUDYDI, USUBJID

ITTFL

TRTP, TRTPN

PARAM, PARAMCD

AVAL

STARTDT, ADT

CNSR

EVNTDESC

AGE

SEX

Parameter DEATH PFS

Results Days to Death Days to Progression Free Survival


Goal of Metadata

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• 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


Goal of Metadata (2)

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• 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.


Cons

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• 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?


Pros (1)

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• 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.


Pros (2)

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• Better estimate on the number of ADaM datasets – help the planning and resourcing.

• Review on Mock Up tables and SAP


Conclusion

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• The concept of Metadata is “Plan your work and work your plan”

• ADaM Metadata is ongoing until all are done.


Questions?

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