SDTM modelling: from study protocol to SDTM-compliant datasets

4,849 views
4,556 views

Published on

Biometristi Italiani Associati – Seminario BIAS
CDISC SDTM and ADaM: Moving from theory to practice
SAS Institute – Milano - 14/03/2014

Published in: Health & Medicine
0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
4,849
On SlideShare
0
From Embeds
0
Number of Embeds
16
Actions
Shares
0
Downloads
221
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide
  • Protocol Milestone indicates a protocol-specific point-in-time event
    Disposition event indicates the completion of the study as a whole, or the end of the current Epoch if the Epoch variable is populated
  • SDTM modelling: from study protocol to SDTM-compliant datasets

    1. 1. SDTM MODELLING: FROM STUDY PROTOCOL TO SDTM-COMPLIANT DATASETS - Biometristi Italiani Associati – Seminario BIAS CDISC SDTM and ADaM: Moving from theory to practice SAS Institute – Milano - 14/03/2014 Angelo Tinazzi Cytel Inc., Wilmington Del. USA Succursale de Meyrin – Geneva – Switzerland angelo.tinazzi@cytel.com
    2. 2. Cytel Inc. - Confidential 2[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Disclaimer The information contained in this presentation is based on personal research of the author and does not necessarily represent Cytel Inc..
    3. 3. Cytel Inc. - Confidential 3[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Let’s migrate  Phase III study  First Relapsed or Refractory Acute Myeloid Leukemia  Two arms - Blinded study Case Study Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    4. 4. Cytel Inc. - Confidential 4[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Let’s migrate Prior and “follow-up” cancer treatment Tumor Response (efficacy) including response to prior therapies Combination Therapies Follow-up Other various findings Main Data Challenges SDTM IG V 3.1.2 with Amendment 1 was used Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    5. 5. Cytel Inc. - Confidential 5[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration Approach Gap analysis Understanding source datasets Modelling the Migration Migration Finalize, Validate and Document Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    6. 6. Cytel Inc. - Confidential 6[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Gap Analysis  Initiated prior to commencing migration activities  How to perform gap analysis  Itemization and evaluation of files to support migration activities  Document inventory  Study documents  CDISC Standards  Company Standards / Company Implementation Guidance  Validate sample CRF fields versus source data  External data requirements e.g. central labs  Comparison of protocol amendments/versions against CRF versions  Clarifies the scope and challenges of migration activities  Identifies differences in data collection formats Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    7. 7. Cytel Inc. - Confidential 7[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Understanding Source Datasets  Determine if data  Need to be submitted (e.g. «Any AE» information)  Can be used as it is (structure-wise)  Needs to be transposed and brought to a normalized structure  Need detailed pre-processing  Validate the data for any missing/partial values  e. g. format of date variable Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    8. 8. Cytel Inc. - Confidential 8[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Understanding Source Datasets Data domains first ‘pruning’ AE AEAER CMCMR CMPR PRAML BPP CG NLMU LVEF MARA VS PMBSAIFVPR IFCRE NCNC NPTN SCT EG PE SS RESP LB Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions Events Findings Interventions Special Domains ET CD RA PRA MLTX RD CD RA PRA MLTX RD
    9. 9. Cytel Inc. - Confidential 9[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Understanding Source Datasets Data domains first ‘pruning’ – Multiple sources SDTM Raw Datasets AE AE AEAER CM CMCMR CMPRIOR PRAML BPP DM DEMO SCEL DS DS DEMO DS RD ET EX IFVPR IFCRE IE IE (only violated criteria) MH MH CH PSC DX VS VS PMBSA YG NCNC NPTN SCT ZG CG MARA LVEF NLMU ZR PRAMLTX CD RD RA VS VS PMBSA <Not submitted> ETH Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    10. 10. Cytel Inc. - Confidential 10[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  The annotated CRF provides the migration team with a clear presentation of SDTM variables  Completed following the GAP analysis and prior to migration  Experience needed to create the annotated CRF  Knowledge of the SDTM Implementation Guide and Metadata Submission Guidelines (chapter 4 – Guidelines for Annotating CRFs) Annotated CRF Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    11. 11. Cytel Inc. - Confidential 11[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Upon receiving all required information, start defining mapping rules.  The mapping rules should be defined from source datasets (raw data) to target datasets (SDTM)  Key components  SDTM standards and Controlled Terminology files  Study documents including original Annotated CRF  Standard template for specifications  Standard mapping rules to be used (e.g. ISO date conversion, rename, derive etc.) Additional Specifications Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    12. 12. Cytel Inc. - Confidential 12[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Adapt study terminology to standard CDISC (NCI) terminology (CT)  The mapping needs to be described in the define.xml  CT not only restricted to only those values that are available in the data  All entries capitalized for CDISC CT  ‘Spelling’ as per external dictionary (e.g. MedDRA) Controlled Terminology Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    13. 13. Cytel Inc. - Confidential 13[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Mapping to CDISC (NCI) Controlled Terminology e.g. Concomitant Medications route Controlled Terminology Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions Source CDISC/NCI CT INFUSION PARENTERAL Administration by injection, infusion, or implantation MOUTH/THROAT ORAL Administration to or by way of the mouth TOPICAL-EYE OPHTHALMIC TOPICAL PO TOPICAL
    14. 14. Cytel Inc. - Confidential 14[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Mapping to CDISC (NCI) Controlled Terminology e.g. Laboratory Unit Controlled Terminology Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions CDISC/NCI CT Source 10^9/L X 10 9/L X1000/MM3 X10^3/MM3 10^6/L X10 6/UL X10^3/ML umol/L MICROMOL/L
    15. 15. Cytel Inc. - Confidential 15[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Domain that contains a clear representation of the design of a clinical trial Created prior to CRF annotation and data migration Experience needed to create the trial design data set:  SDTM Trial Design Concepts  Experience with key clinical documents (e.g. Protocol, SAP, Data Sets, CSR) Trial Design Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    16. 16. Cytel Inc. - Confidential 16[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Subject Reference Start (RFSTDTC) / End Date (RFENDTC)  E.g. first / last dose  Planned (ARM/ARMCD) vs Actual Arm (ACTARM/ACTARMCD) DM Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    17. 17. Cytel Inc. - Confidential 17[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Relative to Subject Reference Date (RFSTDTC)  Standard Derivation Relative Study Days –DY –STDY --ENDY Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document ConclusionsIf (--STDTC<DM.RFSTDTC) then –STDY=--STDTC-DM.RFSTDTC Else –STDY=(--STDTC-DM.RFSTDTC)+1 SDTM does not allow for Study day 0
    18. 18. Cytel Inc. - Confidential 18[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Prior anti-cancer therapies in CM Mapping Details – Categories in standard domains The new PR domain available in IG 3.2 may be used to store Surgery or other procedures Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    19. 19. Cytel Inc. - Confidential 19[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Check that none of the existing published domains will fit the need  Use existing models as prototype or choose the appropriate general observation class  How to determine where data belong in the SDTM IG v3.1.3 section 8.6  Assign a 2–letter domain code. Possible convention:  Z- for findings  Y- for interventions  X- for events Mapping Details – New Domains Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    20. 20. Cytel Inc. - Confidential 20[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Other Findings (ZG)  Survival Status (ZS)  Tumor Response (ZR)  Other non-protocol cancer therapies (YG) Mapping Details – New Domains Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions New SS (Subject Status) domain available in IG 3.2
    21. 21. Cytel Inc. - Confidential 21[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Other non-protocol cancer therapies (YG) Mapping Details – New Domains Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions The Interventions class captures investigational, therapeutic and other treatments that are administered to the subject (with some actual or expected physiological effect) either as specified by the study protocol (e.g., exposure to study drug), coincident with the study assessment period (e.g., concomitant medications), or self-administered by the subject (such as use of alcohol, tobacco, or caffeine). SDTM IG v3.1.3 Section 2.4
    22. 22. Cytel Inc. - Confidential 22[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Other non-protocol cancer therapies (YG) Mapping Details – New Domains Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions STUDYID USUBJID DOMAIN YGSEQ YGSPID YGSTDTC YGENDTC XXXX YYYYYY YG 1 1 2011-01-12 2011-02-20 XXXX YYYYYY YG 2 1 2011-01-12 2011-02-25 YGTRT YGCAT YGSCAT FTC PLUS SORAFENIB SUBSEQUENT NON-PROTOCOL AML TREATMENTS CHEMOTHERAPY CLAG-M THERAPY SUBSEQUENT NON-PROTOCOL AML TREATMENTS CHEMOTHERAPY Interventions Qualitfiers 2.2.1 Select and include the relevant Qualifier variables from the identified general observation
    23. 23. Cytel Inc. - Confidential 23[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Other non-protocol cancer therapies (YG) Mapping Details – New Domains Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions Solicited information in the CRF
    24. 24. Cytel Inc. - Confidential 24[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration The Disposition dataset provides an accounting for all subjects who entered the study and may include protocol milestones, such as randomization, as well as the subject's completion status or reason for discontinuation for the entire study or each phase or segment of the study, including screening and post-treatment follow-up. Sponsors may choose which disposition events and milestones to submit for a study. See ICH E3, Section 10.1 for information about disposition events. Mapping Details – Disposition (DS) SDTM IG v3.1.3 Section 6.2.2 Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    25. 25. Cytel Inc. - Confidential 25[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Mapping Details – Disposition (DS) Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions  Decide what to store in DS  Protocol Milestone vs Disposition Event
    26. 26. Cytel Inc. - Confidential 26[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration AE, CM, DM, DS, EX, LB, MH, VS, YG, ZG, ZR, ZR Domains Requiring Supplemental Qualifier Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions SUPPDM SUPPCM
    27. 27. Cytel Inc. - Confidential 27[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  RELREC  AE <---> CM  ZR <---> CM  ZR <---> YG  Supplemental Qualifier (SUPPXX)  One per each domain where supplemental qualifiers are required  It should be not used as a waste basket Identifying Relationship Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions FDA CDER Common Data Standards Issues Document
    28. 28. Cytel Inc. - Confidential 28[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Identifying Relationship – ZR vs CM The link requires also USUBJID (here hiden) Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions ZR contains also tumor response to prior anti-cancer therapies stored in CM e.g. chemotherapy
    29. 29. Cytel Inc. - Confidential 29[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Identifying Relationship – ZR vs CM CM RELREC ZR The link requires also USUBJID (here hiden) Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    30. 30. Cytel Inc. - Confidential 30[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration Because study arms are combining two treatments, there was the need of collecting relationship and action taken related to the two drugs. The experimental drug make use of AEACN and AEREL in AE, while for the combination drug Supplemental Qualifiers were required Identifying Relationship – SUPPAE The link requires also USUBJID (here hiden) AE SUPPAE Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    31. 31. Cytel Inc. - Confidential 31[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration  Split Domains if needed (dataset size >1GB)  By Category (--CAT) or sub-category (--SCAT) e.g. LBCAT in LB (HEMATOLOGY CHEMISTRY, etc.)  Imputations are not allowed in SDTM e.g. laboratory results such as ‘<50’ assigned to LBORRES (char variable) while LBORRESN (numeric version) will be empty  assumption for ‘<‘50’ in ADaM Additional points to consider Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions FDA CDER common data standard issues document
    32. 32. Cytel Inc. - Confidential 32[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration  Understanding Specifications  Developing migration programs (e.g. SAS)  Transformation type  Auto  Convert Data Types e.g. numeric to text  Rename  Convert Values e.g. Adaptation of CT  Convert ISODate  Concatenate e.g. in DSTERM main term plus details  Compute (any user-defined SAS® code logic)  Identify derivations common to all domains e.g. COMVAR temp dataset to store keys, important date  SAS Macros to assist in standardizing the migration process (e.g. ISO date conversion, Controlled Terminology Look-ups) Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    33. 33. Cytel Inc. - Confidential 33[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration VSVSVitalsVitals Source Dataset Variable Target Dataset Variables VITALS.STUDYID VS.STUDYID Auto VITALS.USUBJID VS.USUBJID Auto VITALS.VISITNUM VS.VISITNUM Auto VITALS.VISIT VS.VISIT Auto Mapping Logic Direct Variables Mapping Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    34. 34. Cytel Inc. - Confidential 34[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration Pre-processing Mapping Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions VSVSVitalsVitals Source Dataset Variables Target Dataset Variables VITALS.SYSBP VS.VSTESTCD Transpose- Name Auto VITALS.DIABP VS.VSTESTCD Transpose- Name Auto VITALS.PULSE VS.VSTESTCD Transpose- Name Auto VITALS.RESP VS.VSTESTCD Transpose- Name Auto VITALS.TEMP VS.VSTESTCD Transpose- Name Auto VITALS.WEIGHT VS.VSTESTCD Transpose- Name Auto VITALS.HEIGHT VS.VSTESTCD Transpose- Name Auto Mapping Logic Pre- processing
    35. 35. Cytel Inc. - Confidential 35[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration ©2014 Cytel Statistical Software & Services Pvt. Ltd. Select SDTM Version here Select SDTM Version here Set various folder paths here Set various folder paths here Tools to facilitate the mapping - MapGene Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    36. 36. Cytel Inc. - Confidential 36[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration Pick a source datasetPick a source dataset Pick a target dataset (in this case SDTM) Pick a target dataset (in this case SDTM) ©2014 Cytel Statistical Software & Services Pvt. Ltd. Tools to facilitate the mapping - MapGene Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    37. 37. Cytel Inc. - Confidential 37[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration “Auto” mapping using smart rules “Auto” mapping using smart rules ©2014 Cytel Statistical Software & Services Pvt. Ltd. Tools to facilitate the mapping - MapGene Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    38. 38. Cytel Inc. - Confidential 38[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration Tools to facilitate the mapping - MapGene Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    39. 39. Cytel Inc. - Confidential 39[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Migration Tools to facilitate the mapping - MapGene Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    40. 40. Cytel Inc. - Confidential 40[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document  Remove duplicates when it is clear the «Not Done» applies to a certain category of assessments Finalize - Final ‘pruning’ SDTM IG v3.1.3 Section 4.1.5.1.2 “TESTS NOT DONE “ Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    41. 41. Cytel Inc. - Confidential 41[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document  Downsize variable length Variable length should be assigned based on actual stored data to avoid to minimize file size  Exception for  All variables with identical names in different SDTM domains e.g. USUBJID, STUDYID, VISIT, EPOCH  --DTC variables (always $19) Finalize - Final ‘pruning’ H Y P E R K A L E M I A AETERM Length=14 H Y P E R K A L E M I A Length=12 “Warning” issued by Validation Check SD1081 Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions FDA CDER Common Data Standards Issues Document
    42. 42. Cytel Inc. - Confidential 42[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document  Actual protocol events (SV and SE) from migrated SDTM  Identify key variables / Sorting  --SEQ generation  Use of special characters  E.g. any ASCII code not within 32-126  Additional within domain consistency  Same LBSTRESU within the same LBCAT LBSPEC LBMETHOD Finalize – Additional Steps Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    43. 43. Cytel Inc. - Confidential 43[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document SDTM can be only finalized at the time of db-lock Unplanned Visits  Numbered based on chronological order Medical Coding to be completed Unexpected Controlled Terminology  Laboratory units to harmonize to Controlled Terminology  Free text for Partial Date XPT Generation Finalize Possible “Warning” / “Errors” issued by OpenCDISC •SD0080 - AE start date is after the latest Disposition date •SD0081 - Observation date is after the latest Disposition date •SD0002 - NULL value in AEDECOD variable marked as Required Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    44. 44. Cytel Inc. - Confidential 44[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document  QC of Migration of Clinical Data e.g. double programming and blinded if possible  Compliance to SDTM standards (OpenCDISC)  Re-program of key statistical outputs e.g. compare outputs created with original raw data and compare with outputs created from SDTM converted datasets Validate Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    45. 45. Cytel Inc. - Confidential 45[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document  «Justify» errors / warnings  Provide additional instructions / details  Help the reviewer understanding the data structure  Useful ‘hints’ for stats/programming team !!!! «Original» information may not in the location where you would expect to be !!!!! Document - Reviewer Guide Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    46. 46. Cytel Inc. - Confidential 46[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document Document - Reviewer Guide Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    47. 47. Cytel Inc. - Confidential 47[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document Document - Reviewer Guide Additional Key Instructions Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    48. 48. Cytel Inc. - Confidential 48[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Finalize, Validate and Document Document - Reviewer Guide Document Deviations Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions  Unexpected variable for a domain belonging to an observation class where the variable is allowed  E.g. Severity of Medical History
    49. 49. Cytel Inc. - Confidential 49[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Conclusions  ADaM is the right place for «derivation», but actually migrating to SDTM implies the «shake» of original source data  Migrating to SDTM is not just a matter of renaming variables  It could be challenging for biostats sometime to find / locate the required information Let’s migrate Migration Approach Gap Analysis Understanding datasets Modelling the migration Migration Finalize, Val, Document Conclusions
    50. 50. Cytel Inc. - Confidential 50[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Questions
    51. 51. Cytel Inc. - Confidential 51[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Q&A Q: Does SDTM requires british or american english? A: Standard NCI terminology should be used, while for free text original entries should be kept e.g. investigator specifications
    52. 52. Cytel Inc. - Confidential 52[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Q&A Q: Should study in a submission up-coded to the same Medical Dictionary version? E.g. MedDRA for AEs A: Yes if an ISS (Integrated Safety Summary) is submitted, then a single version of MedDRA should be used FDA CDER Common Data Standards Issues Document
    53. 53. Cytel Inc. - Confidential 53[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration TA Identifying Elements and Trials Arms - PLANNED TE
    54. 54. Cytel Inc. - Confidential 54[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration TV Identifying Elements and Trials Arms - PLANNED +TI +TS
    55. 55. Cytel Inc. - Confidential 55[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS Modelling the Migration SV Identifying Elements and Trials Arms - ACTUAL SE
    56. 56. Cytel Inc. - Confidential 56[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS An example Project Weeks W0 CytelClient W1 Share documents Annotate CRF Understanding Study Datasets Gap Analysis Submit datasets Migration Validation Provide information Develop Mapping specifications Create Define.XML Review Review Communicate the results /issues Confirmation on specs Submit Confirmation on datasets Final submission • Study protocol CY21- 002, CRF, SAP etc. • Datasets • Other informative documents • Study protocol CY21- 002, CRF, SAP etc. • Datasets • Other informative documents • Compare source dataset as against CRF • Inform in case of missing documents • Compare source dataset as against CRF • Inform in case of missing documentsShare required information Share required information W2 W3 W4 W5
    57. 57. Cytel Inc. - Confidential 57[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS An example Project Weeks CytelClient Share documents Annotate CRF Understanding Study Datasets Gap Analysis Submit datasets Migration Validation Provide information Develop Mapping specifications Create Define.xml Review Review Communicate the results /issues Confirmation on specs Submit Confirmation on datasets Final submission W0 W1 W2 W3 W4 W5
    58. 58. Cytel Inc. - Confidential 58[A. Tinazzi] SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS An example Project Weeks CytelClient Share documents Annotate CRF Understanding Study Datasets Gap Analysis Submit datasets Migration Validation Provide information Develop Mapping specifications Create Define.xml Review Review Communicate the results /issues Confirmation on specs Submit Confirmation on datasets Final submission Receive specs approvalReceive specs approval • Develop and validate datasets as listed in the scope document • Submit - Datasets - SAS programs - Support documents • Develop and validate datasets as listed in the scope document • Submit - Datasets - SAS programs - Support documents Receive Confirmation on datasets Receive Confirmation on datasets Create Define document and submit all deliverables Create Define document and submit all deliverables W0 W1 W2 W3 W4 W5

    ×