What’s New in CDISC - Lex Jansen · – Specification for the Analysis Results Metadata extension to the Define-XML Version 2 – Based on ADaM Model v2.1 – Released 30 JAN 2015

Restricted © Business & Decision Life Sciences/Assero Limited 2016

What’s New in CDISC Business & Decision Life Sciences: Peter Van Reusel & Nick De Donder Assero: Dave Iberson-Hurst 11 OCT 2016


Agenda

CDISC Model Update

Recent FDA Feedback

PMDA


Agenda

CDISC Model Update

Recent FDA Feedback

PMDA






TAUG Status SEP 2016


SHARE Milestones 2016


SHARE Milestones 2017


CDASH

  CDASHIG v2.0 –  Minor updates and clarifications –  New domains have been added to correspond to newer SDTMIG v3.2

domains –  Open for public review until 16 August 2016

  CDASH Model v1.0 –  Support creating of new domains –  Ensures that the collected data are aligned with the protocol data

requirements –  Open for public review until 16 August 2016


SDTM

  SDTM v1.6 (expected soon) -  Domain-specific variables for the general observation classes -  Subject and trial disease milestones -  Additional variables to support SEND, PGx, Medical Devices and Human

Clinical Trials

  SDTMIG v3.3 -  New domains, variables and concepts -  Decommissioning of MO and PE -  Updates of rules and labels -  Batch 3 open for public comments until 21 OCT 2016

  SDTMIG-PGx v1.0 –  IG for Pharmacogenomics and Pharmacogenetics –  Provisional release May 2015: based on draft version of SDTM v1.5


SEND

  SENDIG v3.1 –  Based on SDTM v1.5 –  New Cardiovascular and Respiratory domains –  New variables for MI and EG, changes to VS –  Corrections to SENDIG v3.0 –  Released 7 JUL 2016

  SEND-DART v1.0 –  New IG for Developmental and Reproductive Toxicology –  Embryo-Fetal Developmental Toxicity Studies –  Based on SDTM v1.5 –  Released 16 AUG 2016

  Future Developments –  Dermal / Ocular Modeling –  Genetic Toxicology Modeling


SEND vs. SDTM

Supplemental Qualifiers –  Can only be created for domains belonging to the General Observation

Classes

  Trial Design

–  SEND does not use TV, TI, TD –  SEND uses TX (Trial Sets)

Subject Pooling –  POOLDEF domain

Tumor.xpt –  Tumor Dataset for Statistical Analysis –  The following domains are required for the creation of this dataset:

•  DM (Demographics) •  DS (Disposition) •  EX (Exposure) •  MI (Microscopic Findings) •  TF (Tumor Findings) •  TX (Trial Sets)


Medical devices

  CDASH domains –  Develop metadata and forms for 7 domains –  Complete: DI, DR, DT, DO, DX, DE –  Open: DU

Implementation Guide

–  Update MD-IG with new materials –  Results in MD-IG V2.0: expected release end 2016

  Components/Granularity –  New RELDEV domain –  Allows definition of any number of components in any number of levels

  ADaM –  ADSL replaced by ADDL


ADaM

  Current version: ADaM V2.1 and ADaMIG V1.1

ADaMIG –  Version 1.2: Add new variables to ADaMIG v1.1

–  Version 2.0: Align ADaM Model v2.1 with ADaMIG v1.2 and Define v2.0

AResM v1 –  Specification for the Analysis Results Metadata extension to the Define-

XML Version 2 –  Based on ADaM Model v2.1 –  Released 30 JAN 2015

  OCCDS v1 –  General Occurrence Data Structure –  Released 16 FEB 2016: based on draft version of ADaMIG v1.1


XML Technologies

  Define-XML User Guide –  New Implementation Wiki User Guide for Define.xml

  Define.XML v2.1 –  Update of Define.xml schema

  CTR-XML v1.0 –  Released 28 MAR 2016

  ODM v2.0 –  Updated to support wearable data –  Development is ongoing

  Protocol-XML –  Deferred to 2016

  RDF SHARE –  Export became available in Q4 2015


Agenda

CDISC Model Update

Recent FDA Feedback

PMDA


JumpStart uses SDTM Tabulations

eCRF(Standardized) SDTM

Analysis(ADaM

Preferred)StudyReport

Output Report

  JumpStart uses the following domains:

–  Data Fitness à all datasets submitted for a trial –  Safety Analysis à DM, DS, EX, AE, LB and VS

Actuallycollected May not exactly match


Data Fitness Findings Flow

SDRG/DefineFile SupplementalInfo ControlledTerminology

Deaths MissingData CDERCommonIssues Duplicates

TermMatching StandardUnits SafetyPopulaGon Race/Ethnicity


Data Quality Issues

  Define File

  Study Data Reviewer’s Guide

  Disposition (DS) Domain

  Items in Technical Conformance Guide (TCG)

  Other Issues

DefineFile SDRG DSDomain ItemsinTCG

OtherIssues

Source: PhUSE CSS Washington 2016 – Mary Doi (FDA)


Define File

  Use Define.xml v2.0 –  Lacking a complete Define file greatly increases the amount of time reviewers spend

understanding an application

  Include detailed description of data elements: –  Detailed, reproducible computational algorithms for derived variables –  Code lists that describe categories, subcategories, reference time-pts –  Applicable value level metadata & description of SUPPQUAL domains –  Explanations of sponsor-defined identifiers (e.g., –SPID, -GRPID)

  Provide separate unit code lists for each domain

DefineFile


Study Data Reviewer’s Guide

  Provide SDRG for each data package with each section populated (TCG 2.2)

–  Missing (or incomplete) in 35% of applications –  Lacking a complete SDRG greatly increases the amount of time reviewers spend

understanding an application

  Fix all possible issues identified by FDA Validation Rules

  Include clear and detailed explanation for all “non-fixable” issues (TCG 2.2)

  Provide Data Flow diagram that shows traceability between data capture, storage, and creation of datasets

SDRG


Disposition Domain

  Include time-point information about the event in Disposition records, not just when the event was recorded (include start dates for Disposition events)

  Include records regarding subject study completion and last follow-up contact with subject in DS domain

  Accurately code reasons why subject did not complete the study or study treatment

DSDomain


Technical Conformance Guide

  Provide Trial Design domains that are complete and accurate (TCG 4.1.1.3)

–  Trial Summary domain missing in 15% of applications –  Down to 8% (2015, n=24) from 30% (2014, n=10)

  Include EPOCH variable in all appropriate domains (AE, LB, CM, EX, VS, DS) (TCG 4.1.4.1)

–  Missing in 79% of applications

  Use Baseline Flags in LB and VS (TCG 4.1.4.1) –  Missing baseline tests or flags in 29% of applications

ItemsinTCG


Technical Conformance Guide

  Use CDISC controlled terminology variables when available (TCG Section 6)

–  Controlled terminology issues in 62% of applications

  Include Seriousness Criteria for all serious adverse events (TCG 4.1.1.3)

–  Missing (or with inconsistencies) in 50% of applications –  Important to independently verify that AE was serious

  Include study day variable for all observational datasets (TCG 4.1.4.1)

ItemsinTCG


Other Issues

  Remove duplicate records –  59% with duplicate issues –  Duplicate records in the LB, VS, and EG domain with potentially contradictory

information make it difficult to summarize results

  Provide AE Treatment Emergent Flag in SUPPAE domain –  68% missing AETRTEMFL

  Convert to standard units consistently for laboratory data –  21% missing (or inconsistent) Standard Units for labs when original units were given

  Provide all AEDECODs –  13% missing at least one AEDECOD

OtherIssues


Agenda

CDISC Model Update

Recent FDA Feedback

PMDA


PMDA study data review

Source: CDISC Interchange Chicago 2015 – Yuki Ando (PMDA)


PMDA Timeline for Implementation

Source: CDISC Interchange Chicago 2015 – Yuki Ando (PMDA)


Notifications & Guides Released for Industry

  Technical Conformance Guide on Electronic Study Data Submissions

  Published 27 April 2015

  Provisional translation July 2015

–  Explains technical details regarding e-study data submission

–  Subject to updates based on the

accumulated experience and/or the revisions of the data standards


Notifications & Guides Released for Industry

  Notification on Practical Operations of Electronic Study Data Submissions

  Published 27 April 2015

  Provisional translation July 2015

–  Explains practical issues regarding the introduction of electronic submissions of study data for new drug applications

–  States the start date of e-study data submission for NDA


Notifications & Guides: Content

  PMDA specific validation rules with own severity message

  SDTM datasets & ADaM datasets as SAS XPORT file transport format version 5

  Analysis Result Metadata required

  Specific rules related to handling of Japanese text

  Programs to be submitted for the creation of ADaM datasets


Thank you. Barcelona, Spain, 11 OCT 2016


Business & Decision Life Sciences 141 rue Saint-Lambert

B-1200 Brussels T: +32 2 774 11 00 F: +32 2 774 11 99

[email protected] http://www.businessdecision-lifesciences.com/

Peter Van Reusel | Data Standards Advisor | +32 476 54 59 17 | [email protected] Nick De Donder | Line Manager Data Standards | +32 476 82 20 27 | [email protected]

Dave Iberson-Hurst | Data Standards Expert | +44 7989 60 37 93 | [email protected]

Assero Limited 58 Third Avenue

Teignmouth, TQ14 9DP, United Kingdom T: +44 7989 603793

http://www.assero.co.uk/

Documents

What’s New in CDISC - Lex Jansen · – Specification for the Analysis Results Metadata extension to the Define-XML Version 2 – Based on ADaM Model v2.1 – Released 30 JAN 2015