Evolution of SDTMIG to 3.1.2: A mapping specialist must reference on these changes

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1 PharmaSUG Paper CD04 Evlutin f SDTMIG t 3.1.2: A mapping specialist must reference n these changes ABSTRACT Rachit Desai, eclinical Slutins, New Lndn, CT Anirudh Gautam, MaxisIT, Metuchen, NJ Vikash Jain, eclinical Slutins, New Lndn, CT With the evlutin f changes t the SDTM data standards mdel which incrprated in minr and majr changes t the Classes, Dmains, Variables, Cntrlled Terminlgy and its respective assumptins in SDTMIG versin has played a great deal f effrts fr a mapping specialist t understand these evlving changes and their respective principals been implementatin in cmpliance t these data standards and keep themselves updated n this knwledgebase with their nging wrk with in the industry t keep them in par with the cmpetitive glbal market. This paper will further dive int the details f the new dmains incrprated in the current versin and als give an verview and details n their structure and its respective implementatin with real case scenaris. The purpse f this presentatin is t benefit the user by prviding a clear cmparisn f changes incrprated t these standards and its impact t implemented standards in previus versins and als discusses further n the new guidelines utlines n which bservatin class the data belngs t was nt part f the previus versins f implementatin guide. INTRODUCTION The SDTM submissin data standards mdel has been evlving since its intrductin in the year The current SDTM v3.1.2 is the latest standard available and als accepted by FDA since 6 Nvember 2009 fr electrnic submissin f data. The current versin has cme a lng way since its intrductin, but here we wuld be cmparing it with the previus apprved versin (3.1.1) The key changes t v3.1.2 are fr been utline fr the fllwing sectins: Additin f new dmains NCI gverned Cntrlled Terminlgy Dmain level changes t pre-existing dmain mdels Changes t Assumptins fr Dmain Mdels Dmain level changes We will nw drive int the details f new additins and changes t the standards fr each if the abve sectins utlined. Additin f new dmains in Mdel fr Special Purpse dmains Subject Element (SE) and Subject Visits (SV): The Trial Elements, Trial Arms, and Trial Visits datasets in the Trial Design mdel describe the planned design f the study but it is als necessary t cllect

2 the crrespnding actual data. Subject assignment t an Arm is reprted in the ARM variable in Demgraphics. Actual Elements and Visits data fr each subject are described in tw additinal datasets: The Subject Elements dataset (SE) The Subject Visits dataset (SV) (SE) and Subject Visits (SV) are mved under special-purpse dmain datasets frm Trial Design mdel. Additin f new dmains in General Observatin Class (Events) Prtcl Deviatin (DV): The DV dmain is an Events mdel fr cllected prtcl deviatins and nt fr derived prtcl deviatins that are mre likely t be part f analysis. Events typically include what the event was, captured in --TERM (the tpic variable), and when it happened (captured in its start and/r end dates). The intent f the dmain mdel is t capture prtcl deviatins that ccurred during the curse f the study (see ICH E3, Sectin 10.2). Usually these are deviatins that ccur after the subject has been randmized r received the first treatment. This dmain shuld nt be used t cllect entry criteria infrmatin. Vilated inclusin/exclusin criteria are stred in IE. The Deviatins dmain is fr mre general deviatin data. A prtcl may indicate that vilating an inclusin/exclusin criterin during the curse f the study (after first dse) is a prtcl vilatin. In this case, this infrmatin wuld g int DV. Clinical Events (CE): The intent f the dmain mdel is t capture clinical events f interest that wuld nt be classified as adverse events. The data may be data abut episdes f symptms f the disease under study (ften knwn as signs and symptms), r abut events that d nt cnstitute adverse events in themselves, thugh they might lead t the identificatin f an adverse event. Fr example, in a study f an investigatinal treatment fr migraine headaches, migraine headaches may nt be cnsidered t be adverse events per prtcl. The ccurrence f migraines r assciated signs and symptms might be reprted in CE. Other studies might track the ccurrence f specific events as efficacy endpints. Fr example, in a study f an investigatinal treatment fr preventin f ischemic strke, all ccurrences f TIA, strke and death might be captured as clinical events and assessed as t whether they meet endpint criteria. Nte that ther infrmatin abut these events may als be reprted in ther datasets. Fr example, the event leading t death wuld be reprted in AE and death wuld als be a reasn fr study discntinuatin in DS. Additin f new dmains in General Observatin Class (Findings) PK Cncentratins (PC): PK Cncentratins dmain mdel cntains data cllected abut tissue (e.g., serum r plasma) cncentratins f analytes (usually study drugs and/r their metablites) as a functin f time after dsing the study drug.

3 Example: PK Parameters (PP): PP Definitin: Data describing the parameters f the time-cncentratin curve fr PC data (e.g., area under the curve, Cmax, Tmax). It is recgnized that PP is a derived dataset, and may be prduced frm an analysis dataset that might have a different structure. As a result, sme spnsrs may need t nrmalize their analysis dataset in rder fr it t fit int the SDTM-based PP dmain Drug Accuntability (DA): Drug Accuntability is fr data regarding the accuntability f study drug, such as infrmatin n receipt, dispensing, return, and packaging. Micrbilgy Specimen (MB): The MB dmain is designed t stre micrbilgy findings that include rganisms fund, grain stain results and rganism grwth status. Micrbilgy Susceptibility Test (MS): The MS dmain is designed t stre any findings related t the rganisms fund and submitted in MB. This will usually cnsist f susceptibility testing results, but can als be ther rganism-related findings such as extent f grwth f an

4 rganism. This dmain is intended t be used in cnjunctin with the MB dmain described abve. Findings Abut: Findings Abut Events r Interventins is a specializatin f the Findings General Observatin Class. Findings Abut dmain needs t be used when cllected CRF data represent an Event r Interventin which can nt be part f Event/ Interventin r Supplemental Qualifier. Example: Pre-Specified Adverse Events In this example, three AEs are pre-specified and are scheduled t be asked at each visit. If the ccurrence is yes, then a cmplete AE recrd is cllected n the AE frm. Pre-Specified Adverse Events. The Findings Abut recrd and the AE recrd may be linked via RELREC NCI gverned Cntrlled Terminlgy Fr SDTMIG V3.1.1 the presence f a single asterisk (*) r a duble asterisk (**) in the Cntrlled Terms r Frmat clumn indicated that a discrete set f values (cntrlled terminlgy) was expected fr the variable. This set f values was spnsr-defined in cases where standard vcabularies had nt yet been defined (represented by *) r frm an external published surce such as MedDRA (represented by **). Fr V3.1.2, cntrlled terminlgy is nw represented ne f three ways which is been gverned by NCI: A single asterisk when there is n specific CT available at the current time, but the SDS Team expects that spnsrs may have their wn CT and/r the CDISC Cntrlled Terminlgy Team may be develping CT A list f cntrlled terms fr the variable when values are nt yet maintained externally The name f an external cde lists whse values can be fund via the hyperlinks in either the dmain r Appendix C frm SDTMIG apprved versin The current list f cntrlled terminlgy is lcated n the CDISC website at

5 Dmain level changes t pre-existing dmain mdels Additin f new variables fr respective dmains Dmain: CONCOMITANT MEDICATIONS CM Added new variable CMPRESP, CMSTRTPT, CMSTTPT, CMENRTPT Dmain: ADVERSE EVENTS AE Added new variable AEPRESP, AEENRTPT, AEENTPT Dmain: SUBSTANCE USE SU Added new variable SUPRESP Dmain: MEDICAL HISTORY MH Added new variable MHPRESP, MHENRTPT, MHENTPT Dmain: PHYSICAL EXAMINATION PE Remved expected variable PESTRESN and PESTRESU Dmain: EXPOSURE EX Added permissible variables EXVAMT and EXVAMTU Changes t Assumptins fr Dmain Mdels Submissin f free text Data cllected as free text is usually a part f a list f chices and accmpanied by Other, specify. The placement f free-text value wuld differ as per the belw mentined scenaris. When assciated with a nn-result qualifier then the free text value shuld be included in the SUPPQUAL. But when the free text value is assciated with a qualifier field then the spnsr may chse t either include it in SUPPQUAL r directly in the qualifier variable field within the dmain. If the free text value is assciated with a result field then the free text is always included in the Original result (--ORRES) and its up t the spnsr t either include the full/partial free text value in the character result (--STRESC) r put OTHER. Fr Interventin and Events class, the respective Tpic variables can have the free text value cllected n CRF and --PRESP culd be used t distinguish between pre-specified and free text respnses. Fr Findings class, TEST wuld have the value f the free text and TESTCD wuld have t cded. Splitting Dmains This is a cmpletely new assumptin that has been intrduced in versin which allws the spnsr t split a dmain int physically different datasets by a nn missing categry r sub-categry. There are certain rules that need t be fllwed s as t ensure that the spitted dmains can be appended back tgether. Gruping and Categrizatin f variables The spnsr may chse t categrize a tpic variable int --CAT and --SCAT s as t uniquely identify a recrd, hwever these values shuld nt be redundant within --DECOD and --BODSYS. The implementatin guide als suggests n hw t grup variables and hw des --GRPID differ frm --CAT and --SCAT.

6 Hierarchy f Gruping Variables STUDYID DOMAIN --CAT --SCAT USUBJID --GRPID Assignment f Natural Keys Variables cntributing t the natural key fr a dmain shuld be included in the metadata. These are nt static fr a dmain mdel and may differ frm spnsr t spnsr based n the cllectin f the data s as t uniquely identify a recrd within a dmain. This prvides freedm t the spnsr t include result variables as a part the natural key. Origin f Metadata fr Variables The SDTMIG defines certain cntrlled terms that wuld ppulate the Origin clumn f the define.xml. These cntrlled terms are as fllws: CRF Fr data cllected n the CRF edt Fr data received via electrnic Data Transfer. Applicable fr lab, ECG r IVRS Derived Fr variables derived by the Spnsr based n an algrithm frm ther data values Assigned Fr variables that are either cded as a part f cding prcess (-- DECOD) r values set independently s as t fill SDTM fields (DOMAIN etc.) Prtcl Fr variables having values cming frm the prtcl as a part f the trial (EXDOSE, VSPOS etc.) Submitting multiple values fr a variable A Tpic variable, fr an Interventin (--TRT) r Event (--TERM) class, may have multiple values reprted. Fr such cases the spnsr usually either reslves the multiplicity r splits the values in t independent recrds. A Result variable fr a Finding class (--ORRES) having multiple values reprted fr a test must be submitted in multiple recrds fr the same test (--TESTCD). But in rder t preserve uniqueness f the data, the spnsr may chse t include result variable as a part f the natural key fr that dmain. Multiple values fr a Qualifier variable must be stred in the SUPPQUAL f the dmain and the value fr the Qualifier variable shuld be MULTIPLE. The values f QNAM and QLABEL shuld be mre specific in rder t clearly link the multiple values with its Dmain. Supplemental Reasn variables The spnsr smetimes cllects the reasn fr smething was dne r nt dne. Then variable --REASND, a part f the general bservatin class, handles the reasn fr nt dne. Similarly --INDC and --ADJ variables are present in Interventin class t handle the reasn fr an interventin. The Findings class

7 has n predefined variable that culd handle such scenari; therefre any reasning value must g t SUPPQUAL. Relative Timing variables The latest versin f SDTMIG (v3.1.2) adds fur new timing variables, -- STRTPT, --STTPT, --ENRTPT, and ENTPT, s as t express relative timing assignments such as Prir r Onging that are cllected at ther times f the study and is nt handled by --STRF and --ENRF variables. Althugh these new variables cntain similar values as --STRF and --ENRF but is nt limited t the study reference perid and can be linked t any timing descriptin. Fr a reference time pint crrespnding t the date f cllectin r assessment, an bservatin can start BEFORE that time pint, can start COINCIDENT with that time pint, r it is unknwn (U) when it started. An bservatin can end BEFORE that time pint, can end COINCIDENT with that time pint, can be knwn that it didn t end but was ONGOING, r it is unknwn (U) at all when it ended r if it was nging. In this case AFTER is nt a valid value because it wuld represent an event after the date f cllectin. If the reference time pint is prir t the date f cllectin r assessment then an bservatin can start BEFORE the reference pint, can start COINCIDENT with the reference pint, can start AFTER the reference pint, r it may nt be knwn (U) when it started. An bservatin can end BEFORE the reference pint, can end COINCIDENT with the reference pint, can end AFTER the reference pint, can be knwn that it didn t end but was ONGOING, r it is unknwn (U) when it ended r if it was nging. Dmain level changes DM Rle f BRTHDTC changed frm Result Qualifier t Recrd Qualifier Changed variable label fr AGE frm Age in AGEU at RFSTDTC t Age t remve names f ther variables in variable labels. AGE des nt have t be derived frm RFSTDTC ARMCD is restricted t 20 characters and nt 8 characters CO Added VISITNUM, VISITDY and VISIT variables IDVAR and IDVARVAL rle changed frm Identifier t Recrd Qualifier and COVAL rle changed frm Result Qualifier t Tpic CM Changed variable label fr CMDOSTOT frm Ttal Daily Dse Using DOSU t Ttal Daily Dse t remve names f ther variables in variable labels EX Added assumptin that Expsure data is required Changed variable label fr EXDOSTOT frm Ttal Daily Dse Using DOSU t Ttal Daily Dse t remve names f ther variables in variable labels EG VISITNUM changed frm Required t Expected EGEVAL changed frm Expected t Permissible

8 LB VISITNUM changed frm Required t Expected PE Remved expected variables PESTRESN and PESTRESU and als remved variable PEBLFL SC SCDTC changed frm Expected t Permissible VS VISITNUM changed frm Required t Expected CONCLUSION The utlined changes and additins described in this paper are the nce described as majr changes in SDTMIG versin. But there are many detail changes at micr level which is a task fr a mapping specialist t keep a clse eye n. These changes t standards are nging and evlving which will be updated in future versins, and always pens up a scpe f reference fr the mapping specialist t refer t such changes, new additin t standards either at class, dmain r variable levels and many mre aspects f the functinality in implementing these standards t streamline the data reprting prcess. REFERENCES CDSIC SDTM Implementatin Guide and ACKNOWLEDGMENTS I wuld like t acknwledge eclinical Slutin fr prviding the pprtunity t wrk n this paper. SAS and all ther SAS Institute Inc. prduct r service names are registered trademarks r trademarks f SAS Institute Inc. in the USA and ther cuntries. indicates USA registratin. CONTACT INFORMATION Yur cmments and questins are valued and encuraged. Please ne f the authrs at: Rachit Desai rdesai@eclinicalsl.cm Anirudh Gautam agautam@egistar.cm Vikash Jain vjain@eclinicalsl.cm r jainvikash77@yah.cm