2CDER’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 exampleIG is updated, as is the FDA’s CIDIdeally, column widths should only be the maximum length used in that column across recordsSolution:Should we use extra characters used or %?Exceptions?
3CDER’s Top Issues Dataset Sizes Description: Solution: Based on FDA’s SDS and CIDSolution:Limit set to 1 gbWarning acceptable for this?Should warning/error be based on certain limits?Warning 1 gb to 1.25 gbError > 1.5?
4CDER’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 imputedIncorrect value for --DY variableSolution:Someone brought up an issue with thisExtra rule check or edit of existing rule check?Is warning appropriate?
5CDER’s Top Issues Duplicate USUBJID/--DECOD/--STDTC record Description:E.g. AEs with same start dateSituation for imputed dates?Solution:Add rule or modify to exclude any partial dates in recordsChange to information if partial date?
6CBER’s Top (open) Issues Project Breakout SessionMarch 18-19, 2013
7CBER’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?
8CBER’s Top Issues * SD0006: No Baseline Result in [domain] for subject Description:While SDTM requires baseline, not all tests have a “baseline” valueIs 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?
9CBER’s Top Issues* SD0026/29/35: Standard unit null when standard result is providedDescription:Implementation issue? EDC?Or is the issue that not all LBTESTs have associated unit?Proposal:Identify rules with no units and update implementationDefine.xml or TS domain for list of tests w/o unitAdd additional variable to indicate LBTEST has no unitUtilize screen failure if applicable?
10CBER’s Top IssuesSD0031: Missing values for --STDTC and --STRF, when --ENDTC or --ENRF is providedDescription:Data collection issueCon meds for ongoing, so have ENRF but no start informationProposal:Adjust business rule on how to represent exposures that happen in a “moment in time”CT for situations where started before trial but now ongoingSTRTPT could be used to represent event/intervention occurred prior, but would need to amend IG for clarification
11CBER’s Top Issues SD0063: SDTM/Dataset variable label mismatch Description:Variable label should match label described in SDTMWhen creating a new domain Variable Labels could be adjusted as appropriate to properly convey the meaning in the context of the data being submittedThere 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?
12CBER’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” studyRandomized but not “treated” -> perhaps subject diedPhase 0 study looking at population but no treatment being providedSolution:ACTARMCD provided in which allows NOTTRTOpenCDISC can check this to increase accuracy of rule validationImportant review piece for FDA reviewers
13CBER’s Top IssuesSD0087/88: RFSTDTC/RFENDTC is not provided for a randomized subjectDescription: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?
14CBER’s Top Issues * CTxxxx: Many Codelist Issues Description: Invalid codelist value not found in codelistThis is not necessarily an extensible codelist vs. SDTM codelist issueProposal:When using extensible codelists, reference needs to be made in define.xmlThis will eliminate “most” CT issues in your OpenCDISC report which arose due to faulty define.xmlUpdate define.xml code specifying external code list dictionary
15Project Breakout Session March 18-19, 2013 CDER’s Top IssuesProject Breakout SessionMarch 18-19, 2013
16CDER’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 itemsDefine.xml is anotherSolution:Create new checks? Is this business rule specific?
17CDER’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/analyzeIf duration field is inputted in expected start/stop, is this detected?Solution:Create new checks? Is this business rule specific?
18CDER’s Top Issues Traceability Description: Solution: Being able to trace data between CRFs/SDTM/ADaMFDA reviewers want this, but how do you provide?Very, very difficult to solve this issueSolution:?
19CDER’s Top Issues SD0064: Invalid subject Description: Solution: Subject in non-DM domain but no record in DMRecorded information but subject did not receive treatment? Withdrew prematurely?Solution:Does ACTARMCD provide solution?Use screen failure and add information to ACTARMCD?
20CDER’s Top Issues SD0038: Study Day value = 0 Description: Solution: IG is clear that Study Day can be -1 or 1, but not 0Understanding or implementation issue?Solution:Discuss OpenCDISC v1.4’s new checks for this
21CDER’s Top IssuesSD0080: AE start date is after the latest Disposition dateDescription:Sometimes, this last disposition date not recordedOther times, protocol requires follow-up period for AEs while the disposition date is listed in original trial scheduleSolution:Modify checks?
22CDER’s Top Issues SD1005: Invalid StudyID Description: Proposal: StudyID values don’t match StudyID in DMThis seems like a simple issue to resolve -> why does this happen?This metadata checking is important to FDA processesIssues 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
23CDER’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) domainIs this a data quality check issue?
24CDER’s Top IssuesSD0040: Inconsistent value for --TEST within --TESTCDDescription: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 nameWhy would this be different?
25CDER’s Top Issues SD0005: Duplicate --seq Description: The value of Sequence Number (--SEQ) variable must be unique for each record within a subjectWhy would this occur?Is this because a subject comes in twice for a single sequence because no data reported in first sequence?
26CDER’s Top Issues SD0004: Inconsistent value for DOMAIN Description: Domain Abbreviation (DOMAIN) variable should be consistent with the name of the datasetWhy would this ever break?Due to split domains?
27CDER’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?
28CDER’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 underscoresClear and concise explanation -> why does this rule still break so often?
29CDER’s Top IssuesSD0048: 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 providedSeems simple to resolve -> why does this rule break? Other points to consider? Special cases?
30CDER’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 DomainDoes data belong in parent domain and not suppqual?This can (and does) happen -> data dumped into suppqual because not sure where else to put itIf no clear parent, should it be included?Custom domain?
31CDER’s Top IssuesSD0061: Domain referenced in define.xml but dataset is missingDescription:Domains referenced in data definition document (define.xml) should be included in the submissionSeems simple enough to implementPoor define.xml management or other reason?Can compare define metadata with SDTM data library
32CDER’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?
33CDER’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 IGAllows for maximum use of standardized data
35CAB/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 NULLProposed Solution/Action:Requires additional discussion originally sent to CBER Top 20 Validation Rule Failures project team for further discussion.
36CAB/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.
37CAB/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.
38CAB/VP OpenCDISC Proposed Solution/Action: SD0093 Description: 'Age Units (AGEU) should be provided, when Age (AGE) is populatedProposed Solution/Action:Send to Change Control Board to be changed to an error.
39CAB/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.
40CAB/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.