An Efficient Way to Generate, Update and Maintain Define.XML 2.0

Yuan Wang, FMD K&LSeptember 07, 2018

Agenda

04 Pinnacle validation

03 Steps of Generation

02 Components of define.xml v2.0

01 What is define.xml ?

05 Tips to Update and Maintain

What is defne.xml?• Define-XML transmits metadata that describes any tabular dataset

structure. When used with the CDISC content standards, it provides the metadata for human and animal model datasets using the SDTM and/or SEND standards and analysis datasets using ADaM.

• Define-XML is required by the United States Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for every study in each electronic submission to inform the regulators which datasets, variables, controlled terms, and other specified metadata were used.

• CRT-DDS or commonly known as “define.xml”, is not just for SDTM, SENDor ADaM but can even be used for non submission, proprietary data sets.

CDISC Example

Components of define.xml• Dataset definitions• Dataset variable definitions• Controlled Terminology definitions• Value list definitions• Links to supporting documents• Computational method definitions• Comments definitions

Steps to generate define.xml

SDTM/ADaM Spec SDTM/ADaM Data CDISC Controlled Terminology

Excel Define Spec

Define.xml 2.0

SAS

Pinnacle 21 CommuntyAnnotated CRF Reviewer Guide

Example of define spec

Definespec Spreadsheet Define Programs

l Studyl Datasetsl Variablesl Valuelevell Whereclausesl Codelistsl Dictionariesl Methodsl Commentsl Documents

l setup01definel setup02ctl setup03specl step01_doc_dic_studyl step02_datasetl step03_variablel step04_valuelevell step05_codelistl step06_methodl Step07_definespecl 4 macros

Setup is used to define the folder path, macro variables,

read in SDTM CT and specification and convert to SAS

datasets

• Program paths

• Global macro variables

setup01define

• Convert SDTM controlled terminology to

SAS datasets

setup02ct

• Convert mapping specification to SAS

datasets

setup03spec

step01_doc_dic_studyCreate sheet_study sas dataset used for study sheet in define spec.

step01_doc_dic_studyCreate sheet_dictionaries sas dataset used for dictionaries sheet in define spec.

step01_doc_dic_study

step02_dataset

step02_dataset

step03_variable

step03_variable

Origin: CRF: Data that was collected as part of a CRF and has an annotated CRF associated with the variable. Derived: Data that is not directly collected on the CRF or received via eDT, but is calculated by an algorithm or reproducible rule defined by the sponsor, which is dependent upon other data values. Assigned: Data that is determined by individual judgment (by an evaluator other than the subject or investigator), rather than collected as part of the CRF, eDT or derived based on an algorithm. Protocol: Data that is defined as part of the Trial Design preparation. An example would be VSPOS (Vital Signs Position), which may be specified only in the protocol and not appear on a CRF or transferred via eDT. eDT: Data that is received via an electronic Data Transfer (eDT) and usually does not have associated annotations. An origin of eDT refers to data collected via data streams such as laboratory, ECG, or IVRS. Predecessor: Data that is copied from a variable in another dataset. For example, predecessor is used to link ADaM data back to SDTM variables to establish traceability.

step03_variable

step04_valuelevell Value Level Metadata should be provided when there is a need to

describe differing metadata attributes for subsets of cells within a column.

l It is most often used on SDTM Findings domains to provide definitions for Variables such as --ORRES, --ORRESU, --STRES, --STRESU that are specific to each test code (value of --TESTCD) .

l Conventional usage was also attached the SUPP--.QNAM variable in the special class SUPPQUAL.

l In ADaM, value level metadata often describes AVAL or AVALC in BDS data structures based on values of PARAMCD.

step04_valuelevel

step05_method

step06_codelist

step07_definespecl Use all the sheet_ SAS datasets we created before to generate define

spec in .xls format

l Will need to save as to .xlsx format for Pinnacle 21 Community use

Pinnacle Validation

Update define.xml

SDTM/ADaM SpecCDISC Controlled

Terminology SDTM/ADaM Data

Excel Define Spec

Define.xml 2.0

SAS

Pinnacle 21 CommuntyAnnotated CRF Reviewer Guide

Any Questions?