Geneva Branch
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
Cytel Inc. - Confidential
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[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..
Geneva Branch
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Let’s migrate
Case Study
 Phase III study
 First Relapsed or Refractory Acute Myeloid
Leukemia
 Two arms - Blinded study
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Let’s migrate
Main Data Challenges
 Prior and “follow-up” cancer treatment
 Tumor Response (efficacy) including
response to prior therapies
 Combination Therapies
 Follow-up
 Other various findings
SDTM IG V 3.1.2 with Amendment 1 was used
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration Approach
Geneva Branch
Let’s migrate
Migration Approach
 Gap analysis
 Understanding source datasets
Gap Analysis
Understanding datasets
Modelling the migration
 Modelling the Migration
 Migration
 Finalize, Validate and Document
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Gap Analysis
 Initiated prior to commencing migration activities
 How to perform gap analysis
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
 Itemization and evaluation of files to support migration activities
Understanding datasets
 Document inventory
Modelling the migration
 Study documents
Migration
 CDISC Standards
Finalize, Val, Document
 Company Standards / Company Implementation Guidance
Conclusions
 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
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Understanding Source Datasets
Geneva Branch
Let’s migrate
Migration Approach
 Determine if data
Gap Analysis
 Need to be submitted (e.g. «Any AE» information)
Understanding datasets
 Can be used as it is (structure-wise)
Modelling the migration
 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
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Understanding Source Datasets
Let’s migrate
Data domains first ‘pruning’
Migration Approach
Gap Analysis
AE
NCNC
NCNC
Understanding datasets
CMCMR
AEAER
NPTN
NPTN
PRAML
CMPR
DEMO
SCEL
SCT
SCT
Migration
Finalize, Val, Document
CG
DS
IFVPR
VS
LVEF
PMBSA
MARA
RD
DS
Modelling the migration
BPP
NLMU
DEMO
Geneva Branch
ET
IFCRE
PE
LB
MH
RD
CH
PRA
PRA
MLTX
MLTX
PSC
RA
DX
RESP
SS
SS
EG
CD
Events
Findings
Interventions
Special Domains
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Understanding Source Datasets
Data domains first ‘pruning’ – Multiple sources
Geneva Branch
Let’s migrate
SDTM
Raw Datasets
Migration Approach
AE
AE
AEAER
Gap Analysis
CM
CMCMR
CMPRIOR PRAML
DM
DEMO
SCEL
BPP
Understanding datasets
Modelling the migration
DS
Migration
DS
DEMO
DS
EX
IFVPR
IFCRE
IE
IE (only violated criteria)
MH
MH
CH
VS
VS
PMBSA
YG
NCNC
NPTN
SCT
ZG
CG
MARA
LVEF
NLMU
ZR
PRAMLTX CD
RD
RA
VS
VS
<Not submitted> ETH
PMBSA
RD
ET
Finalize, Val, Document
Conclusions
PSC
DX
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Annotated CRF
 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)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Additional Specifications
 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.)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Controlled Terminology
 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)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Controlled Terminology
Mapping to CDISC (NCI) Controlled Terminology
e.g. Concomitant Medications route
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
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
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Let’s migrate
Controlled Terminology
Migration Approach
Mapping to CDISC (NCI) Controlled Terminology
e.g. Laboratory Unit
Gap Analysis
Understanding datasets
Modelling the migration
Migration
CDISC/NCI CT
Source
10^9/L
X 10 9/L
X1000/MM3
10^6/L
X10 6/UL
X10^3/ML
umol/L
MICROMOL/L
X10^3/MM3
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Trial Design
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)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
DM
 Subject Reference Start (RFSTDTC) / End Date
(RFENDTC)
 E.g. first / last dose
 Planned (ARM/ARMCD) vs Actual Arm
(ACTARM/ACTARMCD)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Relative Study Days –DY –STDY --ENDY
 Relative to Subject Reference Date (RFSTDTC)
 Standard Derivation
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
If (--STDTC<DM.RFSTDTC) then –STDY=--STDTC-DM.RFSTDTC
Else –STDY=(--STDTC-DM.RFSTDTC)+1
SDTM does not allow for Study day 0
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Mapping Details – Categories in standard domains
Let’s migrate
Prior anti-cancer therapies in CM
Gap Analysis
Migration Approach
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
The new PR domain available in IG 3.2 may
be used to store Surgery or other procedures
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – New Domains
 Check that none of the existing published domains
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
will fit the need
Modelling the migration
 Use existing models as prototype or choose the
Migration
appropriate general observation class
Finalize, Val, Document
 How to determine where data belong in the SDTM Conclusions
IG v3.1.3 section 8.6
 Assign a 2–letter domain code. Possible convention:
 Z- for findings
 Y- for interventions
 X- for events
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – New Domains
 Other Findings (ZG)
 Survival Status (ZS)
 Tumor Response (ZR)
 Other non-protocol cancer therapies (YG)
Geneva Branch
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
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – New Domains
Other non-protocol cancer therapies (YG)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
SDTM IG v3.1.3 Section 2.4
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).
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Let’s migrate
Mapping Details – New Domains
Other non-protocol cancer therapies (YG)
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
STUDYID
USUBJID
DOMAIN
YGSEQ
YGSPID
YGSTDTC
YGENDTC
Migration
Finalize, Val, Document
XXXX
YYYYYY
YG
1
1
2011-01-12
2011-02-20
Conclusions
XXXX
Interventions
Qualitfiers
2.2.1
YYYYYY
YG
2
1
2011-01-12
2011-02-25
Select and include the relevant Qualifier variables from the
identified general observation
YGTRT
YGCAT
YGSCAT
FTC PLUS SORAFENIB
SUBSEQUENT NON-PROTOCOL AML
TREATMENTS
CHEMOTHERAPY
CLAG-M THERAPY
SUBSEQUENT NON-PROTOCOL AML
TREATMENTS
CHEMOTHERAPY
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – New Domains
Other non-protocol cancer therapies (YG)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Solicited information in the CRF
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – Disposition (DS)
SDTM IG v3.1.3 Section 6.2.2
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.
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Mapping Details – Disposition (DS)
 Decide what to store in DS
 Protocol Milestone vs Disposition Event
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Let’s migrate
Domains Requiring Supplemental Qualifier
Migration Approach
AE, CM, DM, DS, EX, LB, MH, VS, YG, ZG, ZR, ZR
Gap Analysis
Understanding datasets
Modelling the migration
Migration
SUPPCM
Finalize, Val, Document
Conclusions
SUPPDM
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Identifying Relationship
 RELREC
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
 AE <---> CM
Understanding datasets
 ZR <---> CM
Modelling the migration
 ZR <---> YG
Migration
 Supplemental Qualifier (SUPPXX)
 One per each domain where supplemental qualifiers
are required
 It should be not used as a waste basket
FDA CDER Common Data Standards Issues Document
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Identifying Relationship – ZR vs CM
ZR contains also tumor response to prior anti-cancer
therapies stored in CM e.g. chemotherapy
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
The link requires also USUBJID (here hiden)
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Let’s migrate
Identifying Relationship – ZR vs CM
Migration Approach
Gap Analysis
CM
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
RELREC
ZR
The link requires also USUBJID (here hiden)
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Geneva Branch
Let’s migrate
Identifying Relationship – SUPPAE
Migration Approach
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
AE
SUPPAE
The link requires also USUBJID (here hiden)
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Additional points to consider
 Split Domains if needed (dataset size >1GB)
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
 By Category (--CAT) or sub-category (--SCAT)
Understanding datasets
e.g. LBCAT in LB (HEMATOLOGY CHEMISTRY, etc.)
Modelling the migration
Migration
FDA CDER common data standard issues document
 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
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Let’s migrate
 Understanding Specifications
Migration Approach
 Developing migration programs (e.g. SAS)
Gap Analysis
 Transformation type
Understanding datasets
 Auto
Modelling the migration
 Convert Data Types e.g. numeric to text
Migration
 Rename
Finalize, Val, Document
 Convert Values e.g. Adaptation of CT
Conclusions
 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)
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Let’s migrate
Direct Variables Mapping
Migration Approach
Gap Analysis
Vitals
Understanding datasets
VS
Modelling the migration
Source Dataset
Variable
Target Dataset
Variables
Mapping Logic
VITALS.STUDYID
VS.STUDYID
Auto
VITALS.USUBJID
VS.USUBJID
Auto
VITALS.VISITNUM
VS.VISITNUM
Auto
VITALS.VISIT
VS.VISIT
Auto
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Let’s migrate
Pre-processing Mapping
Migration Approach
Gap Analysis
Vitals
VS
Understanding datasets
Modelling the migration
Source Dataset
Variables
Target Dataset
Variables
Preprocessing
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
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Tools to facilitate the mapping - MapGene
Let’s migrate
Migration Approach
Select SDTM
Version here
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Set various
folder paths
here
©2014 Cytel Statistical Software & Services Pvt. Ltd.
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Tools to facilitate the mapping - MapGene
Let’s migrate
Migration Approach
Gap Analysis
Pick a source dataset
Understanding datasets
Modelling the migration
Pick a target
dataset (in this
case SDTM)
Migration
Finalize, Val, Document
Conclusions
©2014 Cytel Statistical Software & Services Pvt. Ltd.
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Geneva Branch
Tools to facilitate the mapping - MapGene
Let’s migrate
Migration Approach
“Auto” mapping
using smart rules
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
©2014 Cytel Statistical Software & Services Pvt. Ltd.
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Tools to facilitate the mapping - MapGene
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
39
[A. Tinazzi]
SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Migration
Tools to facilitate the mapping - MapGene
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
40
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Finalize - Final ‘pruning’
Geneva Branch
Let’s migrate
Migration Approach
 Remove duplicates when it is clear the «Not Done»
applies to a certain category of assessments
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
SDTM IG v3.1.3 Section 4.1.5.1.2 “TESTS NOT DONE “
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Finalize - Final ‘pruning’
Geneva Branch
Let’s migrate
Migration Approach
 Downsize variable length
Gap Analysis
Variable length should be assigned based on actual
stored data to avoid to minimize file size
AETERM
H Y P E R K
Understanding datasets
Modelling the migration
Migration
A L
E
M
I
A
Length=14
Finalize, Val, Document
Conclusions
H Y P E R K
A L
E
M
I
A
Length=12
 Exception for
 All variables with identical names in different SDTM
domains e.g. USUBJID, STUDYID, VISIT, EPOCH
 --DTC variables (always $19)
“Warning” issued by Validation Check SD1081
FDA CDER Common Data Standards Issues Document
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Finalize – Additional Steps
Geneva Branch
Let’s migrate
Migration Approach
 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
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Finalize
Geneva Branch
Let’s migrate
Migration Approach
SDTM can be only finalized at the time of db-lock
 Unplanned Visits
 Numbered based on chronological order
Gap Analysis
Understanding datasets
Modelling the migration
Migration
 Medical Coding to be completed
 Unexpected Controlled Terminology
 Laboratory units to harmonize to Controlled Terminology
 Free text for Partial Date
 XPT Generation
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
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Validate
Geneva Branch
Let’s migrate
Migration Approach
 QC of Migration of Clinical Data
e.g. double programming and blinded if possible
 Compliance to SDTM standards (OpenCDISC)
Gap Analysis
Understanding datasets
Modelling the migration
Migration
 Re-program of key statistical outputs
e.g. compare outputs created with original raw data and
compare with outputs created from SDTM converted datasets
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Document - Reviewer Guide
Geneva Branch
Let’s migrate
Migration Approach
 «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 !!!!!
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Document - Reviewer Guide
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
Cytel Inc. - Confidential
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Document - Reviewer Guide
Additional Key Instructions
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Finalize, Validate and Document
Document - Reviewer Guide
Document Deviations
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
 Unexpected variable for a domain belonging to an
observation class where the variable is allowed
 E.g. Severity of Medical History
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
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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
Geneva Branch
Let’s migrate
Migration Approach
Gap Analysis
Understanding datasets
Modelling the migration
Migration
Finalize, Val, Document
Conclusions
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Questions
Geneva Branch
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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
Geneva Branch
Cytel Inc. - Confidential
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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
Geneva Branch
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Identifying Elements and Trials Arms - PLANNED
TE
TA
Geneva Branch
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Identifying Elements and Trials Arms - PLANNED
TV
+TI +TS
Geneva Branch
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
Modelling the Migration
Identifying Elements and Trials Arms - ACTUAL
SV
SE
Geneva Branch
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
An example Project
Weeks
W0
Client
Study protocol CY21002, CRF, SAP etc.
Gap Analysis
• Datasets
• Other informative
documents Understanding Study
Communicate the
W1
•
W2
Review
W3
Review
W4
•
results /issues
Datasets
Compare source
dataset as against CRF
Annotate CRF
Inform in case of
Share required
Develop Mapping
missing
Submitdocuments
specifications
information
Confirmation on
specs
Migration
Submit datasets
Validation
Confirmation on
datasets
Final submission
W5
Cytel
•
Share
documents
Provide
information
Geneva Branch
Create Define.XML
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
An example Project
Weeks
W0
Client
Cytel
Share
documents
Gap Analysis
Communicate the
results /issues
W1
Provide
information
W2
Review
W3
Review
W5
Understanding Study
Datasets
Annotate CRF
Submit
Confirmation on
specs
W4
Geneva Branch
Submit datasets
Confirmation on
datasets
Final submission
Develop Mapping
specifications
Migration
Validation
Create Define.xml
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SDTM MODELLING: FROM STUDY PROTOCOL TO COMPLIANTS DATASETS
An example Project
Weeks
W0
W1
Client
Cytel
Share
documents
Gap Analysis
Communicate the
results /issues
W2
Provide
information
Receive
specs approval
Review
W3 • Develop and validate
W4
W5
Geneva Branch
datasets as listed in
the scope document
• Submit Review
- Datasets
- SAS programs
- Support documents
Understanding Study
Datasets
Annotate CRF
Submit
Confirmation on
specs
Submit datasets
Confirmation on
datasets
Final submission
Develop Mapping
specifications
Migration
Receive Confirmation on
datasets
Validation
Create Define
document
Create Define.xml
and submit all
deliverables