CDISC in the SEND SEND Team Member of the Japan CDISC Group (JCG)
Outline SEND SEND implementation Guide Ver 2.3 CDISC SDTM SEND SEND 1
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( ) ( ) (ADME ) A:Absorption D:Distribution M:Metabolism E:Excretion 3
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GLP : Good Laboratory Practice 21 9 (1997 )3 26 5
GLP : GLP NonGLP : FDA FDA Format ( ) 6
SEND 7
CDISC, SEND, and the SDTM 2002 SEND CDISC Models SDM Version 3.0 1.x SEND SEND FDA 8
CDISC, SEND, and the SDTM 2004 CDISC Version 1.0 SDTM SEND Models Version 1.x CDISC Version 3.1 Implementation Guide 9
CDISC, SEND, and the SDTM 2005 onwards CDISC Version 1.0 SDTM CDISC Version 3.1 Implementation Guide SEND Implementation Guide 10
Standard for Exchange of Nonclinical Data (SEND) SEND Includes Does not yet include data PharmQuest CDER CRADA (April 2002) SEND CRADA Cooperative Research and Development Agreement NIH CRADA 11
Requirements for Submission of Animal Toxicity Data INDs: 21 CFR 312.23(a)(8)(ii)(b) NDAs: 21 CFR 314.50 (d) Section 505(d) Section 505(d):... 12
Current Approaches for Data Submission ( ) (enda Guidance 1999) PDF ( ) (optional) SAS enda ( flexibility to capture data generated) JMP/SAS : : 13
Future Approach to Data Submission 14
System Architecture SPONSOR FDA RELATIONAL DB Data Sources Transmit Receive FLAT FILES LEGACY SYSTEM Data Integrator And Formatter Data Interchange SEND Format SEND Validator JANUS Tox Vision TM 15
Review Tool ToxVision TM FDA SEND CRADA PharmQuest 16
SEND implementation Guide Ver 2.3 17
Standard for Exchange of Nonclinical Data Implementation Guid Toxicology Studies Version 2.3 1. Introduction 2. Concepts and Terms 3. 4. Domain Models Appendices 18
1. 2. 3. 4. 1.1 1.2 SEND SDTM 2.1 2.2 3.1 / 3.2 Conformance 3.3 SEND 3.4 4.1 : 4.2 : 4.3 : 4.3.1 1 4.3.2 2 4.4 : 4.4.1 2.0 2.1 4.4.2 2.1 2.2 4.4.3 2.2 2.3 19
CDISC SDTM SEND 20
SEND SDTM SEND SDTM FDA STDM SEND and SDTM SEND is based on the SDTM. The SDTM provides a general framework for organizing animal and human study data in electronic format for submission to the FDA. SDTM is available from the CDISC website at http://www.cdisc.org/models/sdtm/v1.1/index.html. Before reading this implementation guide, you should first read the STDM to gain a general understanding of the conceptual model. Future updates to this model are expected to include corrections, expanded guidance for applying model concepts, details on controlled terminology, and additional domain examples in other areas. 21
SEND Domains and Prefixes Dataset Description Interventions EX Exposure BW Body Weights CP Clinical Pathology CS Clinical Signs, PE, and Ophth. DS Disposition DL Drug/Metabolite Levels EG ECG Findings FW GC Food and Water Consumption Group Characteristics MA Macroscopic Findings MI Microscopic Findings OW Organ Weights SC Subject Characteristics SS Study Design Summary VS Vital Signs Special purpose CO Comment 22
Interventions Findings CM: Concomitant Medication EG: ECG Test Results IE: Inclusion/Exclusion Exceptions Events AE: Adverse Events LB: Laboratory Test Results EX: Exposure SU: Substance Use Lab System 001 PE: Physical Examination QS: Questionnaires DS: Disposition Special Purpose SC: Subject Characteristics VS: Vital Signs MH: Medical History DM: Demographics CO: Comments 23
Interventions EG: ECG Findings BW: Body Weights CP: Clinical Pathology CS: Clinical Signs,PE,and Ophth. DS: Disposition EX: Exposure DL: Drug / Metabolite Levels FW: Food and Water Consumption GC: Group Characteristics SC: Subject Characteristics MA: Macroscopic Findings MI: Microscopic Findings Special Purpose CO: Comments VS: Vital Signs OW: Organ Weights SS: Study Design Summary 24
SDTM 1/5 SDTM : Vital Signs (VS) SDTM SEND Variable Name Variable Label Variable Name Variable Label STUDYID Study Identifier STUDYID Study Identifier DOMAIN Domain Abbreviation DOMAIN Domain USUBJID Unique Subject Identifier USUBJID Animal Identifier VSSEQ Sequence Number VSSEQ Sequence Number VSGRPID Group ID VSGRPID Group ID VSSPID Sponsor ID VSTESTCD Vital Signs Test Short Name VSTESTCD Vital Signs Test Short Name 25
SDTM 2/5 SDTM SEND VSTEST Vital Signs Test Name VSTEST Vital Signs Test Name VSCAT Category for Vital Signs VSCAT Category for Vital Signs VSSCAT Subcategory for Vital Signs VSSCAT Subcategory for Vital Signs VSPOS Vital Signs Position of Subject VSORRES Result or Finding in Original Units VSORRES Result or Finding in Original Units VSORRESU Original Units VSORRESU Original Units VSSTRESC Character Result/ Finding in Std Format VSSTRESC Character Reult/ Finding in Std. Format VSSTRESN Numeric Result/ Finding in Std Units VSSTRESN Numeric Result/ Finding in Standard Units VSSTRESU Standard Units VSSTRESU Standard Units 26
SDTM 3/5 SDTM SEND VSSTAT Vital Status VSSTAT Vital Status VSREASND Reason Not Performed VSREASND Reason Not Done VSLOINC LOINC Code VSLOC Location of Vital Signs Measurement VSBLFL Baseline Flag VSBLFL Baseline Flag VSDRVFL Derived Flag VSDRVFL Derived Flag VISIT Visit Name VISITNUM Visit Number VISITDY Planned Study Day of Visit VSDTC Date/Time of Measurements VSDTC Date/Time of Examination 27
SDTM 4/5 SDTM SEND VSDY Study Day of Vital Signs VSTPT Planned Time Point Name VSTPTNUM Planned Time Point Number VSELTM Elapsed Time from Reference Point VSELTM Elapsed Time from Reference Point VSTPTREF Time Point Reference VSTPTREF Time Point Reference 28
29 SDTM 5/5 VS 2004 1202 Y C 37 Rectal temperat ure TEMP VS 401 840415 2004 1202 Y bpm 100 Cardiovascular Heart rate HRTRT VS 401 840415 2004 1202 Y mm Hg 90 Cardiovascular Diastolic blood pressure DIABP VS 401 840415 2004 1202 Y mm Hg 150 Cardiovascular Systolic Blood pressure SYSBP VS 401 840415 VSDTC VSBLFL VSORRESU VSORRES VSS CAT VSCAT VSTEST VSTESTCD DOMAIN USUBJID STUDYID : SEND Required
SEND 1/4 SEND : Organ Weights (OW) Variable Name Variable Label Type Controlled Terms of Format Optionality Usage Notes STUDYID Study Identifier Char Required Unique identifier for a study within the submittion. USUBJID Animal Identifier Char Required Animal identifier. DOMAIN Domain Char OW Required Twocharacter code for the domain most relevant to the observation. OWSEQ Sequence Number Num Required Sequence number given to ensure uniqueness within a dataset for an animal. Can be used to join related records. OWGRPID Group ID Char Expected Ued to link together a block of related records for an animal in a single domain. This is not the treatment group number. OWTESTCD Organ Short Name Char Required Topic variable for OW. 30
SEND 2/4 Variable Name Variable Label Type Controlled Terms of Format Optionality Usage Notes OWTEST Organ Name Char Required Name of the organ examined. OWCAT Organ Weight Category Char ORGWT, ORGBODWT, ORGBRNWT Required Use ORGWT to identify Organ Weight, ORGBODWT to identify Organ Weight/Body Weight Ratio and ORGBRNWT to identify Organ Weight/Brain Weight Ratio. OWORRES Organ Weight Char Expected This field should contain all results, whether numeric or character. OWORRESU Units for Organ Weight Char Expected Units for OWORRES. OWSTRESC Character Result /Finding in Std Format Char Expected Contains the result value for all findings, copied or derived from OWORRES or OWSTRESN in a standard format or standard units. OWSTRESN Numeric Result/ Finding in Std Units Num Expected Used for continuous or numeric results or findings in standard format; copied in numeric format from OWORRES. OWSTRESN should store all numeric test results or findings. 31
SEND 3/4 Variable Name Variable Label Type Controlled Terms of Format Optionality Usage Notes OWSTRESU Standard Units Char Expected Standardized unit used for OWSTRESC or OWSTRESN. OWLOC Organ Location Char Expected Optional description of organ location. For example, Left, Right, Both. OWDTC Date/Time Organ Weighed Char Permissible Date/Time of specimen/tissue collection in ISO8601 format. Used only when different from DSDTC. Otherwise, it should be null(blank). OWSTAT Finding Status Char NOT DONE Permissible Used to indicate a missing finding. Should be Null(blank) if a result exists in ORRES. OWREASND Reason Not Done Char Permissible Describes whey a finding is missing. Used in conjunction with STAT when value is NOT DONE. 32
SEND 4/4 OW STUDYID USUBJID DOMAIN OWTESTCD OWTEST OWCAT OWORRES OWOR RESU OWLOC 840415 401 OW ADRENALS Adrenals ORGWT 43 mg Both 840415 401 OW BRAIN Brain ORGWT 1.9461 gm 840415 401 OW BRAIN Brain ORGBODWT 0.005576 : SEND Required 33
SEND SDTM 34