OpenCDISC Rules for Discussion March 18-19, 2012 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? 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? 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: 1. 2. 3. 4. 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 CDER’s Top Issues Project Breakout Session March 18-19, 2013 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? 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? 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: –? 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? 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 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: – 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: – 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: – 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: – 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 • 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.