OpenCDISC Rules for Discussion March 18-19, 2012

CDER’s Top Issues Wasted Space Description: Solution: 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?

CDER’s Top Issues Dataset Sizes Description: Solution: 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?

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?

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?

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

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?

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?

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?

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

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?

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

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?

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

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

CDER’s Top Issues File System Checks Description: Solution: 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?

CDER’s Top Issues SD0003/1011: ISO Dates Description: Solution: 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?

CDER’s Top Issues Traceability Description: Solution: 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: ?

CDER’s Top Issues SD0064: Invalid subject Description: Solution: 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?

CDER’s Top Issues SD0038: Study Day value = 0 Description: Solution: 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

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?

CDER’s Top Issues SD1005: Invalid StudyID Description: Proposal: 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

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?

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?

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?

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?

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?

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?

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?

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 suppqual because not sure where else to put it If no clear parent, should it be included? Custom domain?

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 enough to implement Poor define.xml management or other reason? Can compare define metadata with SDTM data library

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?

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

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

CAB/VP OpenCDISC SD0031 Description: Proposed Solution/Action: 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.

CAB/VP OpenCDISC SD0046 Description: Proposed Solution/Action: 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.

CAB/VP OpenCDISC SD0081 Description: Proposed Solution/Action: 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.

CAB/VP OpenCDISC Proposed Solution/Action: 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.

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.

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.