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 SessionMarch 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. Identify rules with no units and update implementation2. Define.xml or TS domain for list of tests w/o unit3. Add additional variable to indicate LBTEST has no unit4. 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

• 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

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 SessionMarch 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 SessionMarch 18-19, 2013

• 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.

CAB/VP OpenCDISC