gustav bernard is an associate director at iqvia who has ...€¦ · gustav bernard is an associate...

Gustav Bernard is an Associate Director at IQVIA who has been with the company for 14 years. His work focuses on the implementation of CDISC Standards (SDTM, ADaM and Define-XML) within the IQVIA Global Biostatistics department. He is currently working on creating an ADaM specification creation/automation tool. He is also created the Define-XML 2.0 automation process within IQVIA. Gustav earned a bachelor of business in computer science from the University of the Orange Free State in South Africa.

Zach Dorman is a Senior Statistical Programmer at IQVIA. He has been in the CRO industry for 5 years, and has been a programming team lead on a number of studies for various clients, and has been involved in internal programming initiatives relating to CDISC and Define standards. He attended the University of Reading, United Kingdom for his BSc degree in Applied Statistics.

Copyright © 2017 IQVIA. All rights reserved.

PharmaSUG SDE RTP 2018

Gustav Bernard, Zach Dorman

Define XML

Expectations from

Various Clients, Tools

and Industry

Table of

Contents

2

+ Define XML Expectations from Various Clients, Tools and Industry

• Tools - Pinnacle 21

• Groups – CDISC

• Clients - Industry in General

3

Pinnacle 21

Define XML Expectations from Tools

• Define Datasets Sort Order

- Expected to be Sorted by Class then Alphabetically within Class.

- Newer versions of Pinnacle 21 sorts this list Alphabetically and not by Class

• Variable Level Origin should be missing if Value Level Metadata (VLM) for a Variable has multiple origins.

- Want to make sure everyone is aware of this Define-XML rule.

- Expectation from CDISC Define-XML and Pinnacle 21

- Not clear if this is expected from CDISC SDTM and ADaM Standards.

• WhereClause ID from WhereClauses tab within P21 Specification

- This is being created when latest version of P21 Define Generator is used to create the Define.xml file.

4

Dataset Order


Example Define created with older version of Pinnacle 21, OpenCDISC 2.0.1 Dataset section ordered by Class then

Alphanumeric.

Example Define created with latest version of Pinnacle 21 2.2.0, Dataset section ordered Alphanumerically.

XML Code can be

manually modified

to correct dataset

sort order.

5

Dataset Order


• The order for SDTM datasets is as follows:

- TRIAL DESIGN

- SPECIAL PURPOSE

- INTERVENTIONS

- EVENTS

- FINDINGS

- FINDINGS ABOUT

- RELATIONSHIP

• The Dataset order for ADaM is as follows:

- SUBJECT LEVEL ANALYSIS DATASET

- BASIC DATA STRUCTURE

- OCCURANCE DATA STRUCTURE

- OTHER

6

Quick Intro Into VLM


• VLM Value Level Metadata for SDTM or PARAMETER Value Level Metadata for ADaM

• Test Level Variable Derivation

- If you want to break down how a variable was created on a Test \ Parameter Level.

- Pinnacle 21 Excel Specification

› ValueLevel Tab – Each row will represent a VLM Block to be created.

» Similar Structure to the Variables TAB, but Label column is replaced by a WhereClause Column.

▪ WhereClause Column Links to WhereClauses Tab

▪ Codelist Column Links to the Codelist Tab

▪ Method Column Links to the Methods Tab

▪ Value Level Comment Column Links to the Comments Tab

› WhereClauses Tab contains all the Where Clauses needed to select each of the VLM blocks.

» The Same WhereClause can be used for Multiple Blocks.

▪ So if the Same tests are grouped together for two different Target Variables you will only need one WhereClause

to be used for both.

7

Pinnacle 21: Variable Level Origin when Multiple VLM Origins


• CDISC and P21 Expectation is to have Missing Variable Level Origin if Value Level Metadata has Multiple Origins.

• I would have expected to see the Variable Level Origin to be Derived if there are Multiple Origins within the VLM.

• For Example if you have a dataset where only one test is derived, but all other tests are assigned from SDTM I would

expect the variable to have an Origin of Derived.

Variable Level Missing Origin

Variable Level

Origin Populated

as Expected

8

Visual Illustration

Pinnacle 21: Variable Level Origin when Multiple VLM Origins

VLM for

ADVS.AVAL

with some

Tests having

Origin of

Derived and

Others with

Origin of

Assigned.VLM Block

VLM Block

9

WhereClause ID – Rewritten with Latest version of Pinnacle 21 Tool


• ID Statement in the WhereClauses Tab in an P21 Excel Specification:

• XML code –Define Generator OpenCDISC 2.0.1: XML Code - Define Generator Pinnacle 21 2.2.0:

QID in Define.XML matches the ID in P21 Spec:

WC.ADVS.DTYPE.HEIGHT=WSTCIRS

QID in Define.XML does not match ID in P21 Spec:

WC.ADVS.PARAMCD.IN.HEIGHT-8f625ab5

I Believe this update was made because of a Lack of

unique ID statements in the P21 Specification.

Extract from P21 User Created Excel Spec

10

WhereClause ID – Example where this can be an issue:


• Where This can be a issue:

When you have Multiple Where Clauses that start with

the SAME PARAMCD value, two similar WhereClause

QID’s Will be Created.

Workaround: Ensure that the First Value within a list of

tests used are unique, for the above example if the

values of HEIGHT and WEIGHT are swapped a unique

QID will be created for each entry.

11

QID Naming Convention

Define XML Expectations from Various Groups

• Not enough CDISC guidance on:

- Method and Comment QID Naming Convention, how to name duplicate comments and methods

- Naming convention for VLM non-NCI CT codelists

• List of Comments and Methods at end of a Define-XML File

- Most reviewers of an Define-XML package do not understand the rational for re-listing the comments and Methods in

this section.

- This is the main reason why there needs to be more direction with regards to Comment and Method Naming convention.

- Personally I would prefer if the Standard Stylesheet from CDISC be updated to not show the Comments and Methods

Sections when the define.xml is viewed within a browser.

12


Define XML Expectations from Various Clients, Tools and Industry

SDTM and ADaM Sections. Should the CDISC

Stylesheet be updated to not show the Computational

Algorithms and Comments sections for SDTM Defines

and Analysis Derivations and Comments for ADaM?

Naming of Comments and

Methods are simple when there

is a 1:1 correlation to a

variable.

13



Naming of Comments and Methods are

not as simple when there are not a 1:1

correlation to a variable.

Example when the same comment is

used to derive multiple tests from multiple

domains how do you name that specific

comment?

One way to handle this is to find all

repeat comments or methods and then

assign an Numeric Identifier to this

Comment or Method. Since if you were to

include all datasets, PARAMCD’s and

Variable combinations the ID will be >

than 200 chars.Naming of VLM Non NCI CT Controlled

Terms has no predefined naming

convention. Codelist Name Created

using: DatasetName-Variable-CL-Unique

Identifier

14

QID Naming Convention – Define-XML-2-0-Specification


15

QID Naming Convention - Specification for the Operational Data Model (ODM)


16

CDISC Guidance - Supplemental Variable Naming Conventions


• Conflicting advice about how to reference supplemental variables in Define submissions

• Three known ways that these are requested to be shown by various clients:

1. SUPPxx.QNAM.<variable-name>

2. SUPPxx.QNAM.<variable-name>.QVAL

3. SUPPxx.QVAL where SUPPDM.QNAM = “<variable-name>”

• We recommend the 3rd approach, for the following reasons:

- The first and second approaches are not factually correct as a file path (the variable name is not a valid variable in

supplemental datasets)

- The third approach shows the correct variable path, as well as information on how to populate the variable from the

supplemental dataset.

17

CDISC Guidance - Hyperlinks within Define


• Discrepancies between various browsers in terms of displaying and using hyperlinks to the ADRG and eCRF

• Works in Google Chrome with the style sheet if you use bookmarks

- However, same bookmarks do not work in Internet Explorer

• Using the page number to perform hyperlinking works across both browsers

• Solution: Creation of a Define.html

- This combines XML and the stylesheet, and allows Define packages to be reviewed across any browser

- However, not currently accepted by FDA as acceptable format

18

Industry in General


• In General, misunderstanding in Industry in relation to certain topics that go into a Define

- Makes if difficult for a CRO to apply standard Define processes across multiple clients, for a document that should have

a standard format

• Issues noticed as inconsistent are as follows:

- VLM Grouping within the Define XML

- Use of terminology between standards in Define

- Non-CDISC Defines

- Delivery of Define packages

- Purpose of ADRG

19

VLM Grouping and Format


• Currently, not clear how VLM should be grouped

- Individual row per test OR Grouping of PARAMCD, PARCATx, by types, lengths and comments

• Character VLM Codelists

• For SDTM the Define-XML CDISC examples only use EQ and for ADaM it uses both EQ and IN.

- Not clear why there is a difference between SDTM and ADaM, due to lack of communication

20

Other Define Topics


• Increased requests for creation of Defines for non-CDISC data

- Unsure of whether this can follow the M5 structure for Define packages

• Delivery of Defines across a study

- Vast number of different approaches to how to handle Define deliveries

- Recommendation: Deliver Define package version with each version of the datasets sent

• Creation of Define.pdfs

- Frequent customer request to have PDF files for Define

- Question the need for these – purpose of Define 2.0 is have a printable file, so no requirement for PDFs.

21

ADRG (Analysis Data Reviewers Guide)


• Should the ADRG be the biggest document produced in a clinical trial?

- Clients are moving towards adding all information into the guide

- No considering whether information would be useful for a reviewer (derivations and external data clearly stated in

Define, also listed long-form in ADRG)

- Results in lack of clarity for what was done in the creation of ADaM datasets

• List of programs for submission in ADRG

- Should form part of the Reviewers Guide.

- Uncommon to have a complete list during the creation of the ADRG

- Better communication required between CRO, client and FDA upfront regarding what needs submitting

Questions

• Define XML Expectations from Various Clients,

Tools and Industry.

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