Submission Standards: The Big Picture Gary G. Walker Associate Director, Programming Standards, Global Data Solutions, Global Data Management

Overview of Webinar 1)Clinical Data Standards 2)Regulated Product Submission (RPS) 3)Structured Product Labeling (SPL) Many standards will be touched upon in this standards overview

Clinical Data Standards Topics 1)CDISC SDTM, ADaM, SEND, ODM, CRT-DDS, TDM, PRG, EVS 2)CDASH 3)eCRF (EDC submitted as data) 4)BRIDG 5)CDISC/NCI/FDA EVS and CDED The 18 acronyms above will be explained!

Site to Sponsor to FDA Data Flow MedWatch AE Reports (ICSR) Janus FDA/NCI Analytical Data Warehouse FDA Reviewers Trial Design Sponsor Data Warehouse (ODM) Data Checker and Loader Review Tools CDASH Sponsor Site Data Archive (ODM) ODM Site Interchange: HL7 output file CDISC Content and Interchange CDISC Content* CDASH ODM/XML audit trail SDTM ADaM ODM/XML audit trail

CDISC SDTM CDISC ( Clinical Data Interchange Standards Consortium) SDTM (Study Data Tabulation Model) Designed to guide the organization, structure, and format of standard clinical trial tabulation datasets submitted to a regulatory authority. Contains data that fulfill the requirements for submitting “tabulation” data to the FDA.

CDISC SDTM SDTM (continued) Contains collected and calculated data, coded and un-coded results, and may contain derived data and derived records. Structure of SDTM facilitates the transference of data and the development of tools to re-purpose the SDTM domains (such as presenting the SDTM data as Patient Profiles or Listings).

CDISC ADaM ADaM (Analysis Data Model) Provides metadata models and examples of analysis datasets that are used to generate the statistical results for a regulatory submission. Builds on the SDTM of the submission, adding attributes and examples specific to the statistical analysis.

CDISC SEND SEND ( Standard for Exchange of Nonclinical Data ) Based upon the same fundamentals of the SDTM, but designed to accommodate the data from animal toxicology studies. Some necessary differences, such as litter information, etc. Provides similar benefits as SDTM.

Site to Sponsor to FDA Data Flow MedWatch AE Reports (ICSR) Janus FDA/NCI Analytical Data Warehouse FDA Reviewers Trial Design Sponsor Data Warehouse (ODM) Data Checker and Loader Review Tools CDASH Sponsor Site Data Archive (ODM) ODM Site Interchange: HL7 output file CDISC Content and Interchange CDISC Content* CDASH ODM/XML audit trail SDTM ADaM ODM/XML audit trail

CDISC ODM ODM (Operational Data Model) A vendor neutral, platform independent format for the interchange and archiving of clinical trial data. Includes the clinical data along with its associated metadata, administrative data, reference data and audit information.

CDISC ODM ODM (Operational Data Model) (continued) All of the information that needs to be shared among different software systems during the setup, operation, analysis, submission or for long term retention as part of an archive is included in the model. Based on XML ( eXtensible Markup Language ) CRT-DDS ( Case Report Tabulation – Data Definition Specification ) a.k.a. “Define.XML” - Based upon ODM.

Site to Sponsor to FDA Data Flow MedWatch AE Reports (ICSR) Janus FDA/NCI Analytical Data Warehouse FDA Reviewers Trial Design Sponsor Data Warehouse (ODM) Data Checker and Loader Review Tools CDASH Sponsor Site Data Archive (ODM) ODM Site Interchange: HL7 output file CDISC Content and Interchange CDISC Content* CDASH ODM/XML audit trail SDTM ADaM ODM/XML audit trail

TDM and PRG TDM (Trial Design Model) Trial Design started as a component of the SDTM to describe the time and events schedule to allow comparison between the protocol plan and execution. Trial Design was expanded and became a team of the PRG (Protocol Representation Group), a joint project of CDISC and HL-7 (Health Level 7).

TDM / PRG (cont.) The PRG is charged with identifying standard elements of a clinical trial protocol that can be further elucidated and codified to facilitate study design, regulatory compliance, project management, trial conduct and data interchange among consumers and systems.

TDM / PRG (cont.) The protocol consumers, may include trial registries, regulatory authorities, IRBs, statisticians, project managers, site personnel and users of any downstream systems for the management of clinical trial information.

Trial Design / PRG (cont.) The TDM has published “TDM Part 2” which adds functionality to describe the scheduling of Trial Activities such as assessments, interventions, and administrative actions. It also provides a new concept called Trial Arm Segments to describe trials with dissimilar Arms. Trial Design team is also working on UML diagrams as part of the BRIDG Model.

Site to Sponsor to FDA Data Flow MedWatch AE Reports (ICSR) Janus FDA/NCI Analytical Data Warehouse FDA Reviewers Trial Design Sponsor Data Warehouse (ODM) Data Checker and Loader Review Tools CDASH Sponsor Site Data Archive (ODM) ODM Site Interchange: HL7 output file CDISC Content and Interchange CDISC Content* CDASH ODM/XML audit trail SDTM ADaM ODM/XML audit trail

CDASH CDASH ( Clinical Data Acquisition Standards Harmonization ) To develop a set of ‘content standards’ (element name, definition, metadata) for a core set of global industry-wide data collection fields that will support clinical research studies. The initial scope will be the ‘safety data/domains’ to support clinical trials.

CDASH CDASH leverages the work of the CDISC Terminology team for examples of data variables and code lists. The Terminology team has worked with NCI (National Cancer Institute). NCI is the distributor of the CDISC terminology code lists via the Enterprise Vocabulary Services (EVS) on the NCI web site.

CDED proposal CDED (Clinical Data Element Dictionary) CDISC’s board has received a proposal to develop this dictionary of data element definitions. The purpose of a data element definition is to define each data element with words or phrases that describe, explain, or make definite and clear its meaning.

CDISC-HL7 Message This is an HL7 effort to create HL7 V3 messages from existing content within the CDISC standard. This project will specifically include: a)study summary, b)eligibility criteria, c)trial design (including parts I and II: arms, elements visits, planned assessments, and planned intervention(s)), d)statistical analysis plan, e)collected data/study data tabulations and f)derived data/analysis datasets, all of which are currently defined by the CDISC standard

CDISC-HL7 Message The CDISC content will be mapped to four HL7 V3 messages as follows:

Site to Sponsor to FDA Data Flow MedWatch AE Reports (ICSR) Janus FDA/NCI Analytical Data Warehouse FDA Reviewers Trial Design Sponsor Data Warehouse (ODM) Data Checker and Loader Review Tools CDASH Sponsor Site Data Archive (ODM) ODM Site Interchange: HL7 output file CDISC Content and Interchange CDISC Content* CDASH ODM/XML audit trail SDTM ADaM ODM/XML audit trail Thank you for your attention and now Terry Hardin’s presentation