CDISC Italian-Speaking User Group Meeting 16th May, …cdiscportal.digitalinfuzion.com/CDISC User Networks/Europe/Italian... · CDISC Italian-Speaking User Group Meeting 16th May,

CDISC Italian-Speaking User Group Meeting

16th May, 2008

PART 2Generation of SDTM

Niels Both, S-CubedMember of CDISC e3c

S-cubed ApS | Skovbakken 1 | DK-3500 Værløse | Phone: +45 3644 7677 | [email protected] | www.s-cubed.dk

Presentation - Overview

SDTM Compliance check

Mapping process

Legacy data conversions

Building CDISC/SDTM knowhow

Recieving SDTM data from business partner or CRO

Data QC Checks

mailto:[email protected]

http://www.s-cubed.dk


Building CDISC/SDTM Knowhow

If CDISC/SDTM is new in an organistion, in my expirience itis a good way forward to let a few individuals start up theprocess and then later let them become the super users.

If the CDISC standards are to be implemented within yoursystems, it is important to have buy-in from the topmanagement. To convince them, the following can be keymessages: 1) SDTM will become mandatory for submissions 2) There is a solid business case for using industry

standards3) CDISC is part of the critical path initiative.




Building CDISC/SDTM KnowhowSome options:

• CDISC Training courses, in particular the SDTM training

• The CDISC Interchanges several each year, US and Europe are big events

• Participate in local user group

• Road shows

• READ THE DOCUMENTS!






Mapping process




Data QC Checks





Points to consider prior to legacy conversion:

• Do you have the relevant documents and old data available (ie annotated CRFs, Protocols, DM and data entry guidelines)?

• Do you have the sufficient SDTM knowledge in the company?

• Do you have programming/mapping capabilities and systems inhouse?





Advice:

• Communicate with FDA OBPS prior to submission.

• Do not neglect the time consuming data QC process in the end.

• Follow the SDTM rules as exactly as possible.

• Expect surprises, and put extra time in your project plans.




Mapping processDataset Specification:

Input DataSet Output Dataset Macros

ADVERSE_EVENT AE .

Variable Specification:Input Var Output Var Format

PATNO USUBJID $16

RAW_TERM AETERM $200

Data AE (KEEP=USUBJID AETERM);Set ADVERSE_EVENT;

Format USUBJID $16.;USUBJID=PATNO;

Format AETERM $200.;AETERM=RAW_TERM;

Run;




Mapping processDataset Specification:

Input DataSet Output Dataset Macros

CORE_PATIENT DM .

Variable Specification:Input Var Output Var Format

PATNO USUBJID $16

=FLOOR((SCREEN_D-MDY(DOB_MM,DOB_DD,DOB_YY))/365.25)

AGE 8

Data DM (KEEP=USUBJID AGE);Set CORE_PATIENT;

Format USUBJID $16.;USUBJID=PATNO;

Format AGE 8N.;AETERM=FLOOR((SCREEN_D-MDY(DOB_MM,DOB_DD,DOB_YY))/365.25);

Run;




Mapping processTool can map SAS datasets in ANY format to SAS datasets in ANY format ie

• Analysis data -> SDTM

• Analysis data -> ADaM

• Raw data -> SDTM

• SDTM -> ADaM

For complex derivations, or tedious standard calculations it’s worthwhile to use a setof standard program pieces to embed.




Mapping processStudy 1Study 1Study 1Study 1Legacy Data

Simple mappings

SDTMMinus

Embedded pieces SDTMV3.1.1

SDTM• without derived vars,• with local CT on testcodes, and•with supplemental qualifiers within the domains

Standard embedded pieces to:• derive variables

(ie - - BLFL and dates)• streamline testcodes• create SUPPQUAL domains• enable creation of different

SDTM version• etc




Mapping process

• There are a number of such tools to be purchased, or it can be programmed inhouse

• MOST CRITICAL PART OF THE MAPPING TOOL IS THE USER FUNCTIONALITY!






Mapping process




Data QC Checks




SDTM Compliance Check

FDA check SDTM data, before they enter their datawarehouse. It is therefore very important that SDTMs submitted have been pre-checked.

They use WEBSdm, the specification is publicly available.

• SAS Proc CDISC

• Use Lincoln WEBSdm checker

• Home grown SAS checker

Look carefully at the check specification available at: http://www.phaseforward.com/products/safety/documents/ValidationChecksPerformedbyWebSDMtm.Q107.pdf



http://www.phaseforward.com/products/safety/documents/ValidationChecksPerfor





SDTM Compliance Check

Remember if you use the SDTMs for submission, that some compliance errors might be acceptable.

They can be mentioned in define.xml or a reviewers guide.

If you are inexperienced with SDTM submissions and with what’s acceptable it’s probably easier to avoid/ eliminate the errors altogether.






Mapping process




Data QC Checks




Data QC Checks

Why QC process?

•Better do if you don´t want the recipient to be the one to point out your mistakes.

• A well planned QC process will allow a faster generation process using less resources or allowing the use of junior resources for programming/mapping.




Data QC Checks

Various manual and electronic QC steps that can be performed on data

1.Electronic compliance checks2.Manual data QC of CRFs / eCRF screendumps against SDTMs3.Comparison of basic counts from SDTMs to Clinical Report4.Comparison of most key statistical analysis from Clinical Report, and

SDTM data5.Electronic comparison across many sets of SDTMs to compare the

data contents




Data QC Checks

1.Electronic compliance checks




Data QC Checks2.Manual data QC of CRFs / eCRF

screendumps against SDTMs• To ensure that all (relevant) data from CRFs are included in SDTMs and that

CRF data-items are not switched around.

• Comparison can be done either on SDTMs on the screen or from SDTM data dump listings (on paper)

• Tedious but very important

• Suggest to do on 3-5 CRFs per study

• Done by assistants with SDTM knowledge, and might be combined with creation or finalisation of SDTM annotated case report forms.




Data QC Checks

4. Comparison of most key statistical analysis from Clinical Report,and SDTM data

• Have experienced statisticians reproduce the most key statistical analyses based on the SDTMs and compare with Clinical Study results

• Will also require some statistical programming skills as the SDTM will not contain the derived variables that are potentially needed




Data QC Checks

5.Electronic comparison across many sets of SDTMs to compare the data contents

• Create a program that can compare the contents of individual variables across many different sets of SDTM, and list and countthem in tables for manual review by individuals with good data understanding ie statistician or data manager.




Data QC Checks

Comparison example with 3 studiesSTUDYID STUDY1 (20) STUDY2(275) STUDY3(65)

USUBJID 1_01 (1)1_02 (1)......

2_001 (1)2_002 (1)......

3_101(1)3_102(1)......

SEX M(15)F(5)

M(150)F(125)

m(35)f(30)

AGE 18-30 18-55 19-47

AGEU YEARS(20) YEARS(275) YEARS(65)

COUNTRY USA(20) USA(150)DEN(100)SWE(25)

SWE(65)

.....

OOOPS!






Mapping process




Data QC Checks





CRO

Pharma

FDA





CRO

Pharma

FDA

Based on the detailed specification make sure you check that the CRO data is checked in a way similar to what the recipent will do

It is much easier to fix the problems up front,and not at submission time.




SDTM Compliance

DOMAIN DM VARIABLE SEX SHOULD BE IN RANGE: (’M',’F','U') IT IS: 'MALE’ FOR USUBJID ='103'.



S-cubed ApS | Skovbakken 1 | DK-3500 Værløse | Phone: +45 3644 7677 | [email protected] | www.s-cubed.dk29



Documents

CDISC Italian-Speaking User Group Meeting 16th May, …cdiscportal.digitalinfuzion.com/CDISC User Networks/Europe/Italian... · CDISC Italian-Speaking User Group Meeting 16th May,