OpenCDISC Rules for Discussion

1. OpenCDISC Rules for Discussion March 18-19, 2012

2. CDER’s Top Issues • Wasted Space • Description: • Currently, sponsors pad column widths by arbitrarily pre-allocation column widths to 200, loosely based on the previous IG example • IG is updated, as is the FDA’s CID • Ideally, column widths should only be the maximum length used in that column across records • Solution: • Should we use extra characters used or %? • Exceptions?

3. CDER’s Top Issues • Dataset Sizes • Description: • Based on FDA’s SDS and CID • Solution: • Limit set to 1 gb • Warning acceptable for this? • Should warning/error be based on certain limits? • Warning 1 gb to 1.25 gb • Error > 1.5?

4. CDER’s Top Issues • Expected –DY variable when –DTC present • Description: • Are these three situations enough? • --DY variable value is not populated • --DY variable value is imputed • Incorrect value for --DY variable • Solution: • Someone brought up an issue with this • Extra rule check or edit of existing rule check? • Is warning appropriate?

5. CDER’s Top Issues • Duplicate USUBJID/--DECOD/--STDTC record • Description: • E.g. AEs with same start date • Situation for imputed dates? • Solution: • Add rule or modify to exclude any partial dates in records • Change to information if partial date?

6. CBER’s Top (open) Issues Project Breakout Session March 18-19, 2013

7. CBER’s Top Issues • * SD0002: Required variable is null • Description: • This issue occurs across domains (LB, AE, TS, FA, etc.) • Why does this occur? EDC system issue? Quality Control? • If value not taken/recorded, how to avoid “null” entry? Screen failure? Explanation in Reviewer’s Guide? • Should check be adjusted if all/majority of values in a variable column are null/missing? Different check?

8. CBER’s Top Issues • * SD0006: No Baseline Result in [domain] for subject • Description: • While SDTM requires baseline, not all tests have a “baseline” value • Is this a CBER issue, or is it ubiquitous? • Proposal: • Should existing rule be split for different LBTESTCDs that do not have a baseline to avoid false positives? • Is this currently in progress?

9. CBER’s Top Issues • * SD0026/29/35: Standard unit null when standard result is provided • Description: • Implementation issue? EDC? • Or is the issue that not all LBTESTs have associated unit? • Proposal: • Identify rules with no units and update implementation • Define.xml or TS domain for list of tests w/o unit • Add additional variable to indicate LBTEST has no unit • Utilize screen failure if applicable?

10. CBER’s Top Issues • SD0031: Missing values for --STDTC and --STRF, when --ENDTC or --ENRF is provided • Description: • Data collection issue • Con meds for ongoing, so have ENRF but no start information • Proposal: • Adjust business rule on how to represent exposures that happen in a “moment in time” • CT for situations where started before trial but now ongoing • STRTPT could be used to represent event/intervention occurred prior, but would need to amend IG for clarification

11. CBER’s Top Issues • SD0063: SDTM/Dataset variable label mismatch • Description: • Variable label should match label described in SDTM • When creating a new domain Variable Labels could be adjusted as appropriate to properly convey the meaning in the context of the data being submitted • There was an issue in OpenCDISC v.1.3 that was resolved -> false positive resolved? Does anyone else see this issue now? • When would this issue arise at your company?

12. CBER’s Top Issues • SD0070: No EX record for subject • Description: • Typical for follow-on studies where exposure occurred in first study so no exposure in “this” study • Randomized but not “treated” -> perhaps subject died • Phase 0 study looking at population but no treatment being provided • Solution: • ACTARMCD provided in 3.1.3 which allows NOTTRT • OpenCDISC can check this to increase accuracy of rule validation • Important review piece for FDA reviewers

13. CBER’s Top Issues • SD0087/88: RFSTDTC/RFENDTC is not provided for a randomized subject • Description: • Why does this issue occur? • What do you all use this information to relay? • Data not collected? Study Design? EDC? • If not collected, is screen failure viable option with explanation in reviewer’s guide? • Proposal: • Smart checks based on study design? Is this possible to even implement?

14. CBER’s Top Issues • * CTxxxx: Many Codelist Issues • Description: • Invalid codelist value not found in codelist • This is not necessarily an extensible codelist vs. SDTM codelist issue • Proposal: • When using extensible codelists, reference needs to be made in define.xml • This will eliminate “most” CT issues in your OpenCDISC report which arose due to faulty define.xml • Update define.xml code specifying external code list dictionary

15. CDER’s Top Issues Project Breakout Session March 18-19, 2013

16. CDER’s Top Issues • File System Checks • Description: • Although OpenCDISC v1.4 checks CID for checks, what about other relevant documents, such as the Study Data Specifications? • Folder structure is one avenue to consider as FDA automates processes that require these items • Define.xml is another • Solution: • Create new checks? Is this business rule specific?

17. CDER’s Top Issues • SD0003/1011: ISO Dates • Description: • ISO date field used as duration spec, not just start/stop (i.e. AE) • Partial dates are difficult to interpret/analyze • If duration field is inputted in expected start/stop, is this detected? • Solution: • Create new checks? Is this business rule specific?

18. CDER’s Top Issues • Traceability • Description: • Being able to trace data between CRFs/SDTM/ADaM • FDA reviewers want this, but how do you provide? • Very, very difficult to solve this issue • Solution: • ?

19. CDER’s Top Issues • SD0064: Invalid subject • Description: • Subject in non-DM domain but no record in DM • Recorded information but subject did not receive treatment? Withdrew prematurely? • Solution: • Does ACTARMCD provide solution? • Use screen failure and add information to ACTARMCD?

20. CDER’s Top Issues • SD0038: Study Day value = 0 • Description: • IG is clear that Study Day can be -1 or 1, but not 0 • Understanding or implementation issue? • Solution: • Discuss OpenCDISC v1.4’s new checks for this

21. CDER’s Top Issues • SD0080: AE start date is after the latest Disposition date • Description: • Sometimes, this last disposition date not recorded • Other times, protocol requires follow-up period for AEs while the disposition date is listed in original trial schedule • Solution: • Modify checks?

22. CDER’s Top Issues • SD1005: Invalid StudyID • Description: • StudyID values don’t match StudyID in DM • This seems like a simple issue to resolve -> why does this happen? • This metadata checking is important to FDA processes • Issues can include: dashes, added date, abbreviated study names, etc… • Proposal: • Add additional checks for other StudyID locations (define.xml, index.xml, stf.xml?) for additional accuracy

23. CDER’s Top Issues • SD0065: Invalid subject visit/visit number • Description: • All Unique Subject Identifier (USUBJID) + Visit Name (VISIT) + Visit Number (VISITNUM) combination values in data should be present in the Subject Visits (SV) domain • Is this a data quality check issue?

24. CDER’s Top Issues • SD0040: Inconsistent value for --TEST within --TESTCD • Description: • All values of Name of Measurement, Test or Examination (--TEST) should be the same for a given value of Short Name of Measurement, Test or Examination (--TESTCD) • 1:1 relationship between test code and name • Why would this be different?

25. CDER’s Top Issues • SD0005: Duplicate --seq • Description: • The value of Sequence Number (--SEQ) variable must be unique for each record within a subject • Why would this occur? • Is this because a subject comes in twice for a single sequence because no data reported in first sequence?

26. CDER’s Top Issues • SD0004: Inconsistent value for DOMAIN • Description: • Domain Abbreviation (DOMAIN) variable should be consistent with the name of the dataset • Why would this ever break? • Due to split domains?

27. CDER’s Top Issues • SD0007: Inconsistent value for Standard Units • Description: • Standard Units (--STRESU) must be consistent for all records with same Short Name of Measurement, Test or Examination (--TESTCD) and Category (--CAT) • Same test in different category is considered, so why does this rule still break?

28. CDER’s Top Issues • SD0018: Invalid value for --TESTCD variable • Description: • The value of a Short Name of Measurement, Test or Examination (--TESTCD) variable should be limited to 8 characters, cannot start with a number, and cannot contain characters other than letters in upper case, numbers, or underscores • Clear and concise explanation -> why does this rule still break so often?

29. CDER’s Top Issues • SD0048: Value for --ORRES is populated, when --STAT is 'NOT DONE' • Description: • Status (--STAT) should be NULL, when Result or Finding in Original Units (--ORRES) is provided • Seems simple to resolve -> why does this rule break?Other points to consider? Special cases?

30. CDER’s Top Issues • SD0077: Invalid referenced record • Description: • Reference record defined by Related Domain Abbreviation (RDOMAIN), Unique Subject Identifier (USUBJID), Identifying Variable (IDVAR) and Identifying Variable Value (IDVARVAL) must exist in the target Domain • Does data belong in parent domain and not suppqual? • This can (and does) happen -> data dumped into suppqualbecause not sure where else to put it • If no clear parent, should it be included? • Custom domain?

31. CDER’s Top Issues • SD0061: Domain referenced in define.xml but dataset is missing • Description: • Domains referenced in data definition document (define.xml) should be included in the submission • Seems simple enoughto implement • Poor define.xml management or other reason? • Can compare define metadata with SDTM data library

32. CDER’s Top Issues • SD0017(others): Variable lengths • Description: • The value of xxxx should be no more than yy characters in length • --TEST, --TESTCD, TSPARM, ARMCD, • Are there extenuating circumstances to these rules where character limits may not be enough? • Adjust OpenCDISC checks to accommodate? • What’s the difference between SD0017 and SD1058? Duplicate rules?

33. CDER’s Top Issues • New check ideas • Check for domains with no records • Why did sponsor submit this domain for ‘review’? • No define.xml present (although define.pdf exists) • Warning for now until included in some documentation or IG • Allows for maximum use of standardized data

34. CAB/VP OpenCDISC Reconciliation – Open Issues Project Breakout Session March 18-19, 2013

35. CAB/VP OpenCDISC • SD0031 • Description: • Start Date/Time of Observation (--STDTC), Start Relative to Reference Period (--STRF) or Start Relative to Reference Time Point (--STRTPT) should not be NULL, when End Date/Time of Observation (--ENDTC), End Relative to Reference Period (--ENRF) or End Relative to Reference Time Period (--ENRTPT) is not NULL • Proposed Solution/Action: • Requires additional discussion originally sent to CBER Top 20 Validation Rule Failures project team for further discussion.

36. CAB/VP OpenCDISC • SD0046 • Description: • All values of Qualifier Variable Label (QLABEL) should be the same for a given value of Qualifier Variable Name (QNAM) • Proposed Solution/Action: • Send to the SDS Team to clarify what the IG should say regarding the uniqueness of these one-to one relationships.

37. CAB/VP OpenCDISC • SD0081 • Description: • Date/Time of Collection (--DTC) should be less than or equal to the Start Date/Time of the latest Disposition Event (DSSTDTC) • Proposed Solution/Action: • Requires additional discussion originally sent to CBER Top 20 Validation Rule Failures project team for further discussion.

38. CAB/VP OpenCDISC • SD0093 • Description: • 'Age Units (AGEU) should be provided, when Age (AGE) is populated • Proposed Solution/Action: • Send to Change Control Board to be changed to an error.

39. CAB/VP OpenCDISC • New Rules for Consideration • RelationshipType (RELTYPE) populated as 'ONE' must not have more than one record present in the RDOMAIN with the corresponding IDVAR. • A DATE/TIME OF COLLECTION is available, but the STUDY DAY OF VISIT/COLLECTION/EXAM is missing. • If both start date of observation and reference date are populated with complete dates, then --STDY should be populated.

40. CAB/VP OpenCDISC • New Rules for Consideration • If both end date of observation and reference date are populated with complete dates, then --ENDY should be populated. • Study Day variable(--DY) is not null but the variables required for the calculation (DM.RFSTDTC and --DTC) are not complete. 2. Study Day variable(--STDY) is not null but the variables required for the calculation (DM.RFSTDTC and --STDTC) are not complete. 3. Study Day variable(--ENDY) is not null but the variables required for the calculation (DM.RFSTDTC and --ENDTC) are not complete.