1. Facilitating Data Integration For Regulatory Submissions
John R. Gerlach; SAS / CDISC Specialist
John C. Bowen; Independent Consultant

2. The Challenge
Creating an Integrated (Harmonized) Collection of Clinical Data for Regulatory Submission
Labor Intensive
Error Prone
Modus Operandi – Ad Hoc Programming

3. The SAS Solution Reporting Tool to Evaluate Pair-wise Data Sets
Meta Data Level
Content Level
Assumptions
Same Data Set Names
Same Variable Names
Expandable

4. Comparison of the DM Data Set in the Left and Right Data Libraries
Meta Data Report
Comparison of the DM Data Set in the Left and Right Data Libraries
( Metadata Level )
================= Left ================= ================= Right ==================
Name Type Length Label Type Length Label
AGE NUM Age in AGEU at … NUM Age in AGEU a t…
AGEU CHAR Age Units CHAR Age Units
ARM CHAR Description of … CHAR Description of …
ARMCD CHAR Planned Arm Code CHAR Planned Arm Code
BRTHDTC CHAR Date of Birth CHAR Date of Birth
* COUNTRY CHAR Country
* DOMAIN CHAR Domain Abbreviation CHAR Domain Abbreviation
RACE CHAR Race CHAR Race
* RFENDTC CHAR Subject Reference End …
RFSTDTC CHAR Subject Reference Start CHAR Subject Reference Start …
* SEX CHAR Sex NUM Sex
SITEID CHAR Study Site Identifier CHAR Study Site Identifier
STUDYID CHAR Study Identifier CHAR Study Identifier
* SUBJID CHAR Subject Identifier …
USUBJID CHAR Unique Subject … CHAR Unique Subject Identifier

5. Content Level Report
Comparison of the AE Data Set in the Left and Right Data Libraries
( Content Level )
Variable Left Right
AESER N N
Y Y
AEREL < Null > DEFINITELY RELATED
N NOT RELATED
Y POSSIBLY RELATED
PROBABLY RELATED
UNLIKELY RELATED

6. SAS Reporting Tool Base SAS Macro Language Data Step Programming
REPORT Procedure
SQL with Dictionary Tables
TABLES
COLUMNS
%data_integrate(study101, study201, AE, HTML=N) ;

7. Meta-Data Level Report Methodology
Determine Both Data Sets Exist.
Obtain Meta Data on Each Data Set.
Perform Match-merge.
Produce Report.

8. Comparison of the AE Data Set in the Left and Right Data Libraries
Meta Data Report
Comparison of the AE Data Set in the Left and Right Data Libraries
( Metadata Level )
================= Left ================ ================== Right ================
Name Type Length Label Type Length Label
AEACN CHAR Action Taken w CHAR Action Taken with …
AEBODSYS CHAR Body System CHAR Body System or Organ Class
AEDECOD CHAR Dictionary-Derived Term CHAR Dictionary-Derived Term
AEENDTC CHAR End Date/Time of Adver CHAR End Date/Time of Adverse …
AEENDY NUM Study Date of End of Event NUM Study Day of End of Event
* AEENRF CHAR End Relative to Reference …
AEHLGT CHAR MedDRA Highest Level … CHAR MedDRA Highest Level …
* AEOUT CHAR AE Outcome CHAR Outcome of Adverse Event
* AEREL CHAR Causality CHAR Causality
* AESDTH CHAR Results in Death
AESEQ NUM Sequence Number NUM Sequence Number
AESER CHAR Serious Event CHAR Serious Event
AESEV CHAR Severity CHAR Severity
AESTDTC CHAR Start Date/Time of … CHAR Start Date/Time of …
AESTDY NUM Study Day of Start of Event NUM Study Date of Start of Event
* AETERM CHAR Reported Term for the … CHAR Reported Term for the …
DOMAIN CHAR Domain Abbreviation CHAR Domain Abbreviation
STUDYID CHAR Study Identifier CHAR Study Identifier
USUBJID CHAR Unique Subject Identifier CHAR Unique Subject Identifier

9. Comparison of the AE Data Set in the Left and Right Data Libraries
Meta Data Report
Comparison of the AE Data Set in the Left and Right Data Libraries
( Metadata Level )
================= Left ================ ================== Right ================
Name Type Length Label Type Length Label
* AEENRF CHAR End Relative to Reference …
* AEOUT CHAR AE Outcome CHAR Outcome of Adverse Event
* AEREL CHAR Causality CHAR Causality
* AESDTH CHAR Results in Death
* AETERM CHAR Reported Term for the … CHAR Reported Term for the …

10. Meta Data Report You Need BOTH Reports!
Assume Meta-data Report Indicates Perfect Match.
Data Level – A Different Matter
Different Versions of MedDRA / WHO Codes
Variable Sex Having Value ‘M’ versus ‘1’
You Need BOTH Reports!

11. Content Level Report Methodology
Identify Character variables, if any.
For each Character variable –
Obtain unique values in the Left data set.
Determine data type of the respective variable in the Right data set. Why?

12. Content Level Report Methodology
Obtain unique values in Right data set.
Store as character values, regardless of data type.
Combine Left and Right data sets keeping
30 observations.
Assign the text ‘< Null >’ for missing value.

13. Content Level Report Methodology
Append data set representing the ith variable to the reporting data set.
Produce the report.
Do it again for Numeric Variables.

14. Data Integration Issue – AEOUT
Left Study Right Study
FATAL FATAL
RESOLVED ONGOING
RESOLVED WITH SEQUELAE RESOLVED
UNKNOWN RESOLVED WITH SEQUELAE
UNRESOLVED
Right side represents a subset of values.
Active Study - “ONGOING” should change status by database lock.

15. Data Integration Issue – AEREL
Left Study Right Study
N Definitely Related
Y Not Related
Possibly Related
Probably Related
Unlikely Related
Dichotomous versus descriptive values.
Unlikely Related & Not Related  N
Other Values  Y

16. Data Integration Issue – AESDTH
Manifested in Metadata report only.
AESDTH variable exists in all studies,
except one.
However, AEOUT exists in the Domain.
AESDTH  Imputed from AEOUT (FATAL).

17. Data Integration Issue – AESEV
Left Study Right Study
LIFE THREATENING <Null>
MILD Mild
MODERATE Moderate
SEVERE Severe
Unknown
Null and Unknown values may be an issue.
Mixed case needs to be converted.

18. Data Integration Issue – ARMCD
Left Study Right Study
PROD_NAME <Null>
PLACEBO DRUG_NAME
PLACEBO
Embarrassing Null value for a Required variable.
DRUG_NAME needs to be re-assigned to PROD_NAME.

19. Data Integration Issue – CMROUTE
Left Study Right Study
INTRAVENOUS I/V IV
Intravenous
Intravenous Direct
Intravenous Injection
Convert various forms of Intravenous.

20. Data Integration Issue – COUNTRY
Left Study Right Study
USA US
ENG
ITA
ISO byte versus 2-byte.

21. Data Integration Issue – RFENDTC
Left Study Right Study
<Null> <Null>
T:00:00
T:00:00
T:00:00
T:00:00
Null value acceptable for Screen failures only.
Date / Time converted to ISO8601 Date only.

22. Data Integration Issue – SEX
Left Study Right Study
M <Null>
F 1
U 2
Left study uses proposed CDISC Control Terminology.

23. Conclusion Data integration -- Part of the IT landscape.
ISS / ISE Submissions
Acquisitions (Differing Proprietary Standards)
CDISC Standards -- No Guarantee for Harmonization Across Studies.
Reporting Tool
Metadata Level
Content Level
Standard Reports Promoting Good Communication.

24. Questions? John R. Gerlach SAS / CDISC Specialist
John C. Bowen
Independent Consultant