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CDISC Standards from Start to Finish

Noble Shore, EmmesDr. Sheena Aris, Emmes

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• Founded in 1977; over 35 years of public health experience• 500+ staff supporting 1,000+ clinical trials and research studies

across a range of diseases• Global reach: Studies in more than 60 countries on six continents• Proven IT capabilities• Diverse range of commercial and government clients• Offices in:

• Rockville, Maryland (HQ)

• Frederick, Maryland

• Bangalore, India

• Vancouver, Canada

Emmes at a Glance

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Goals of CDISC Integration

• Incorporate CDISC into every aspect of protocol design, operations, and analyses

• Give data managers the right tools to produce the mapping themselves

• Standardize for future scalability• Facilitate transfer of data to other organizations and for FDA

submission

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an integrated ecosystem of efficient tools to design, manage

and run your clinical trials

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eClinical Components

• Protocol and Form Builder

• Enrollment/Randomization

• EDC (Data Capture)

• Protocol Monitoring

• SDTM Mapping Tool

• Inventory Tracking with GlobalTraceSM

• Electronic Patient-Reported Outcomes (ePRO)

• Data Import/Export

• MedDRA/WHODrug Coding

• Regulatory Tracking System/Document Management System

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Advantage eClinical Dashboard

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eClinical-CDISC IntegrationWeb Form Builder Protocol and eCRF builder Randomization design EDC System configuration Publish to EDC

EDC Enrollment and randomization Data entry and upload Data quality review, reports, query tracking and resolution SDV and site monitoring E-signatures and locking ODM export (metadata/data, snapshot/transactional) SDTM mapping tool

Reporting Standard, ad-hoc, and custom

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Web Form Builder: Protocol BuilderSDTM version, Controlled Terminology release date added to metadata

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Web Form Builder: Data DictionarySDTM variable (alias), label, and group code(s) added to metadata

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Web Form Builder: Data DictionaryInstant lookup of SDTM variables from IG, and test codes from Controlled Terminology

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Web Form Builder: Codelist EditorSDTM value added to metadata

Instant lookup of controlled terms for mapped SDTM variable

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Publishing to EDC

Web Form Builder

Operational Database

(Test)

SDTM mapping and

QC

Operational Database

(Production)

TabluationDatabase

Analysis and Reporting

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SDTM Mapping Tool: Choose Protocol/DomainThe data manager picks a protocol and domain to edit

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SDTM Mapping Tool: Map a CRFThe Adverse Event CRF has been added to the AE domain. The system has auto-mapped some

fields based on the SDTM variable aliases which the data manager entered in Web Form Builder.

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SDTM Mapping Tool: Map a fieldRight-click one of the SDTM variables to add a new mapping

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SDTM Mapping Tool: Map a fieldSelect a field from the CRF’s source data and choose whether to use the literal value from the

operational database or the SDTM value from the metadata (if defined).

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SDTM Mapping Tool: Auto-validationThe field flashes blue to indicate that the mapping has passed validation.

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SDTM Mapping Tool: Auto-validationIf the user introduces an error while modifying the mapping, the field is highlighted in red until the error is corrected. Here, “PROJIDz” is not found in the source data.

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SDTM Mapping Tool: MedDRA/WHO DrugThe tool also links to the MedDRA and WHO Drug databases. Here, the “Core” value

is no longer in red since we have completed the mapping for a required field.

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SDTM Mapping Tool: Functions

Age/Age Units Inputs: birth date, start date Outputs: age value, age units

CRF data: Inputs: source field, get literal or SDTM value? Output: literal or SDTM value for field

Controlled Test Name Inputs: Controlled Term listname to search (ECG, Lab, etc) Output: description of test

Custom decode Inputs: source field, name of lookup table Output: decoded value

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SDTM Mapping Tool: Functions

Date operations Calculate study day from start date and input date

If/thenMetadata lookup Inputs: source field, get EDC label or SDTM label? Outputs: label from metadata

Reference time point Inputs: start/end of time period, input date Output: controlled term classifying the input date

Units lookupVisit number formatting

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SDTM Mapping Tool: Publish a mappingOnce the data manager is done mapping the fields, (s)he can publish the

mapping, which creates a view of the operational data in the test environment.

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Reporting and Analysis

• Daily ETL process populates tabulation database from operational database

• SDTM views in operational DB become tables in the tabulation DB

• Standardized R and SAS programs generate HTML reports which get posted on access-controlled project/study websites

• SDTM and ADaM datasets used to produce safety reports and CSR

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Future IT Initiatives

• Cross-protocol and interactive reporting tools using SDTM datasets

• Blank forms with SDTM annotations• Expand auto-mapping capabilities• ADaM mapping tools• Advantage eClinical on cloud

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Click to edit Master title styleOverview

Outline CDISC subject matter expert (SME) organization and

team structure Review of the protocol Review of the DCFs Annotations in WFB SDTM Mapping Tool QC and Verifying of domains

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All Together

DCF Design

WFB eCRF design and SDTM annotations

Advantage eClinical data

entry

Data transposition

Mapped to SDTM

Pinnacle 21 validationSAS SDTM database

files created

SAS ADaM database files created

Analysis and TFLs from ADaM

Submission to FDA

Analysis informs new protocol decisions

Protocol Receipt

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Click to edit Master title styleSME Organization

SME Team Lead

Project Lead

Protocol Lead

SMEs are trained internally on Emmesstandards

Attend CDISC courses

Receive internal training on basics of coding

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Click to edit Master title styleReview of the Protocol

Emmes has developed protocol review guidelines that incorporate CDISC requirements Ensure that the criteria length is under 200

characters Placement of the new inclusion/exclusion

criteriaUse of the AESEV Toxicity Grading Scale for most

trials Review to ensure that there is no Day 0 in study

schedule

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Click to edit Master title styleReview of the Protocol

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Click to edit Master title styleReview of the Data Collection Forms

Emmes has CDASH compliant forms repository that can be adapted for various sponsors Ensure that the all the data are collected in a

similar fashion for each study The forms get reviewed by the SMEs for

adherence to CDISC/CDASH standards

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Click to edit Master title style

Verify that the forms ideally contain data going to only one domain Ensure there is no imputing of information Remove comments fields if not absolutely

necessary

Review of the DCFs

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Click to edit Master title style

Are all the key variables necessary for mapping the domain on the form If the form is going to LB domain, are the units being collected for

each test Are terms pre-specified on the form?

Review of the DCFs

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• SDTM Variable

• SDTM Label

• SDTM Groups

• Used for “transposition”

SDTM Annotations

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• How is the eCRF structured?• SDTM-like?

• ZAE (Adverse Events), CM1 (Concomitant Medications)

• One eCRF row One Domain row

• One field One variable OR multiple fields One variable

• Non-SDTM like• VS1 (Vital Signs), LLR (Local Lab Results)

• One eCRF row Multiple Domain rows

• One field One variable OR multiple fields One variable

Determining SDTM Annotations

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• SDTM-Like eCRFs – DV1: Protocol Deviation• SDTM:

• DVTERM – Protocol Deviation Term

• Can contain verbatim term for deviation (often times a codelist)

• Emmes:• DV1TERM – Other deviation specify

• DV1DESCR – Description

• Separate fields capturing a deviation that is not contained on the codelist

• Two or more fields same variable, same row

Determining SDTM Annotations

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• Non-SDTM-Like eCRFs – VS1: Vital Signs• VSTEMPF

• SYSBPA

• DIABPA

• PULSE

Determining SDTM Annotations

SDTM: VSORRES - Multiple rows, one column

Emmes: One row, multiple columns

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• Non-SDTM-Like eCRFs – VS1• VSTEMPF

• SYSBPA

• DIABPA

• PULSE

Mapping: Determining SDTMAnnotations

Same variableDifferent groups

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Click to edit Master title style

WFB Annotations/QC in WFB

Publish to SQL

QC Annotations in SQL

Map Domains/Publish Domains to SQL

QC/ Test Domains in EDC/SQL

Overall Process

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Click to edit Master title styleQC of the SDTM Annotations

Checklists used to verifythat all the variables are annotated as intended

Run a report in WFB to check these issues

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Click to edit Master title style

Annotations are viewed in SQL

Run a SQL queries to validate the transposition of the form

Conflicts column helps to identify where the SMEs need to fix SDTM GROUPs

Same SDTM GROUP and same SDTM variable then you get a conflict

QC of the SDTM Annotations

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Click to edit Master title style

WFB Annotations/QC in WFB

Publish to SQL

QC Annotations in SQL

Map Domains/Publish Domains to SQL

QC/Test Domains in EDC/SQL

Overall Process

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Click to edit Master title styleQC of the SDTM Domains

Checklists used to verifythat all the variables are mapped as intended

Programmatically compare to other similar protocol

Established ‘Gold’ protocol for each project

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Click to edit Master title styleVerifying of the SDTM Domains

Verifying the accuracy includes:

• ensuring that the decode functions are working properly

• Variables are populated as intended

• Dates are in ISO8601 format

• Running the Pinnacle21 open source validator

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Click to edit Master title style

Is this standard units per CDISC Control terminology?Is the LBORNRLO

not reported or is this an error? Are the specimen types

not known?

Is the baseline flag populating accurately?

Verifying of the SDTM Domains

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Click to edit Master title styleAdditional Tools

Creation of a mapping summary that helps programmers Downloads every domain mapped from the SQL

server Shows the verbatim mapping code for each

variable Columns include ‘Codelist’, Protocol, SDTM

version and the three SDTM fields assigned from WFB

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Questions