Challenge in Legacy Studies Converting to CDISC – A Case 在传统的研究挑战转化为CDISC–案例.ppt

1、Challenge in Legacy Studies Converting to CDISC A Case Study from MacroStatWeijin Gan Manager, Macrostat July 2012,Background,12 Legacy studies of the same compound, Neurology disease, CSR Completed. 5 studies, Phase II - Phase III 7 studies, Phase I Phase II Objective : Convert legacy data to CDISC

2、 standard (SDTM/ADaM) for FDA submission. (The submission includes 37 studies in total, 12 studies were done by our group),How to ensure CDISC compliance SDTM / ADaM How to ensure the compliance with CSR How to ensure consistency cross studies,The challenges we face,Raw Data,Blank CRF,SDTM IG,Statis

3、tician,Annotated CRF SDTM,SDTM Spec Excel mapping spreadsheet,CDISC expert review Sponsor review,Programmer,ADaM Spec Excel mapping spreadsheet,Legacy Study CSR,CSR QC Report,Data Flow,ADaM IG,SAP,SDTM Data,ADaM Data,Challenge - SDTM Compliance,How to map CRF data to SDTM Domain 2 core SDTM spec SDT

4、M mapping for all studies aCFR and SDTM spec reviews. 1) STDM IG provide very specific mapping rule and a lot example. 2) Consult CDISC expert for special case. 3) Not every variable have clear mapping solution in SDTM. It can be done in different way,Challenge - SDTM Compliance,CASE2: “Not submitte

5、d”,CASE1 : SP vs. OTH “specified” map to SP “other, specify” map to OTH,Case3: CO vs. SUPP Comment to each domain could go to CO domain or SUPP- domain,Case4: DA vs. EX Drug Accountability CRF may dosage information and should go into EX domain, rather than the DA domain,Challenge - SDTM Compliance,

6、Tools to check SDTM compliance OpenCDISC WebSDM All error messages from OpenCDISC reports need to be checked and resolved All warning messages from OpenCDISC should be commented appropriately,Challenge - SDTM Compliance,Keep aCRF, SDTM spec and SDTM consistent Variables in aCRF match SDTM spec The l

7、ist of Controlled Terminology matches the actual values in the datasets (Value level Metadata) Variable role matches SDTM IG Variable attributes match the datasets The ultimate purpose is to keep the define.xml consistent with the SDTM.,Challenge - SDTM Compliance,Challenge - SDTM Compliance,Example

8、 of Consistency check across aCRF, SDTM spec and SDTM,Develop ADaM specification based on SAP ADaM spec underwent several internal and external reviews SAS program checked about 183 rules from ADaM IG. Such as Name convention Variable attributes Value level matches the ADaM dataset Required variable

9、 in ADSL Data Point Traceability One-to-one mapping of variable value ,Challenge - ADaM Compliance,Example of ADaM compliance check,Challenge - ADaM Compliance,Replicate Key table of CSR Investigate and document discrepancies between output from CDISC dataset and CSR table. Create QC report for each

10、 study Sample of QC report,Challenge - CSR Validation,Without the original program code and analysis dataset, investigating discrepancies was very difficult. Possible reason of discrepancy Different raw data Different version of the WHO drug dictionary / MedDRA Algorithm applied differently, e.g. vi

11、sit mapping, LOCF, imputation of missing values Data issue,Challenge - CSR Validation,Tremendous effort was spent to keep the STDM/ADaM consistent across the studies. Core spec prepared at beginning Core team reviewed aCRF/spec across studies to check the consistency SAS program checks the consisten

12、cy of variable names and attribute across studies,Challenge - Consistency Across Studies,Checking SDTM/ADaM compliance still relies on manual review, especially in the early stages Although there are tools to check compliance, such as openCDISC, WebSDM, these tools only work after SDTM/ADaM datasets

13、 were created. Spotting issues at early stages helps to avoid re-work after SDTM/ADaM creation. Finding major issues at early stages, eg. aCFR mapping, data structure, relies on the statisticians knowledge of CDISC. Tools do help a lot. Full automation of compliance check is not always possible.,Les

14、son Learned,With the general CDISC knowledge, the mapping rule of some special domains or endpoints can be quickly learned from CDISC expert Additional effort is needed to QC and maintain SDTM/ADaM spec, if define.xml will be created.,Lesson Learned,Prepare the programming team with CDISC knowledge is essential Some useful knowledge IS