Genzyme Structured (Protocol) Authoring Proof of Concept Pilotportal.cdisc.org/CDISC User Networks/North America... · Genzyme Structured (Protocol) Authoring Proof ... Reuse quality

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Achieving efficiency by bringing global business process and technology together through standards

Genzyme Structured (Protocol) Authoring Proof‐of‐Concept Pilot

BACUN Meeting20 July 2011

A. Brooke Hinkson, Associate Director, Global Biomedical Informatics, Genzyme

Angela M. Horowitz, Manager, Medical Writing, Genzyme

Strategic, Measurable, Achievable, Realistic and Timely Program

to achieve efficiencies for clinical information processes

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Agenda

● Benefits, Goals and Key Concepts– Topic-Based Structured Content Management (SCM) Benefits– SCM Roadmap– Proof-of-Concept Pilot Goals– Topic-Based Content Architecture Key Concepts– Content Architecture

• Implementation of Standards

● Walk Through of Structured Documents– Genzyme Structured Protocol Template and Sample Structured Protocols– Opportunities for Automated Reuse Beyond the Protocol

● SCM Summary and Q&A

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Topic-Based SCM Benefits Ensure Quality and

Standards

“Quality by Design”

● Ensure document content presents the right information based on approved business practices and standards

– Enforces standard text and vocabulary that's harmonized with data standards, SOPs and "built-in" best practices

– Automated business rules help to validate the content in each document

Enhance Transparency ● Understand where and when the content has been used, clearly expose key messages and findings

– Allows users to understand the downstream impact of changes to content to other business processes/documents

Reduce Rewriting and Review Time

● Reuse quality content “building blocks” of text, data and figures– Reuse of known, approved content, allows author to focus on new content

● Targeted writing and review tasks – Specific topics assigned based on subject matter expertise

Improve “Findability” ● Search and navigate based on subject matter at the “topic” or “document” level

– Robust metadata on topics enables effective search by subject matter extending far beyond traditional "keyword searches”

Enable Service Providers and Collaboration with Business Partners

● Provide controlled access to document content and supporting content/data

– Business partners get the right information to support their work up front, reduce the number of questions and time spent searching for documents

● Assign parallel writing tasks at the “topic” level to external partners– Topic level writing assignments can be spread over time and

carried out in parallel, at any point the document can be published to see the latest version

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SCM Roadmap – Development (Partial)

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Structured Authoring Proof-of-Concept Goals

● Demonstrate the value and feasibility of implementing topic-based structured content for:

– Clinical protocols– Clinical Trial Transparency (CTT) protocol registration

● Provide protocol and CTT requirements for a standards-based centralized metadata management capability (i.e., Metadata Repository [MDR])

● Identify and understand the business process changes needed to perform topic-based structured authoring for clinical protocols and CTT

● Demonstrate automation of protocol content going to other purposes including protocol registration

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Developing a Content Architecture

Begin with an initial topic-based content architecture•A set of Topics defining the content•Metadata describing each Topic

• Artifact, Domain, Content Type, …

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Refine the content architecture by deconstructing legacy documents into their Topics components

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Maintaining a Content Architecture cont…

Establish a governance process to:• Balance the benefit of introducing new content with reuse of standard content

• Ensure quality

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Establish the role of content designer as an expert in application of the content architecture

• Creates initial version of new documents

• Recognizes need for new content

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Topic-Based Content Architecture

Content

Artifact Efficacy Objective

Domain Clinical Study-Objective

Content Type Study Design

Study

Phase Phase 3

Study Design Parallel Group

Control Double blind

Blocks of content such as “Study Objectives”

described by metadata

• “Topics” in the Content Architecture contain reusable content• Metadata describes each Topic based on its subject matter• The metadata is used both to

o Enable search at the “topic level”o Bind Topics to specific kinds of documents

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The Topic Map

• The “Topic Map”references each Topic and defines the content “backbone” of a document

• Topics are bound to the Topic Map based on metadata

Topic

Topic

Topic

Topic

Topic Map

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Publishing Documents From Topics

Reusable Topic PoolReusable Topic Pool Topic MapTopic Map

Metadata RepositoryMetadata Repository

Data and/or Reusable DocumentsData and/or Reusable Documents

As a result, business documents are published in format

As a result, business documents are published in format

Other TopicMaps

Database

• Documents may be published from both topics and previously completed documents• The Topic Map and Publication Metadata* indicate format and where each topic is used• Documents may be published from both topics and previously completed documents• The Topic Map and Publication Metadata* indicate format and where each topic is used

Global Development

Plan

ClinicalProtocol

ClinicalProtocol

SynopsisClinical

TrialRegistration

ClinicalStudy

Report

ClinicalSummaries

Publ

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*Publishing integrates Genzyme Style Guide into the document, e.g., font size, margins, etc…

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Key Concept“Document Design PatternDocument Design Pattern”A relationship between topics defining:– a set of topics to be included in the document– the locations for these topics in the document

For example,the “Objectives, Endpoints and Assessments”

design pattern is in the protocol and study report:

Content Design Patterns for Clinical Documentation

Some “Design Patterns” for Clinical Documents

• Derived Topic Guidance• Controlled Topic Terminology• Objectives, Endpoints and

Assessments• Requirement-Event/Finding-

Assessment• State of Subject – Background• Statement of Procedure

Some “Design Patterns” for Clinical Documents

• Derived Topic Guidance• Controlled Topic Terminology• Objectives, Endpoints and

Assessments• Requirement-Event/Finding-

Assessment• State of Subject – Background• Statement of Procedure

efficacy objective

safety objective

efficacy endpoint

safety endpoint

efficacy assessment

safety assessment

Study Objectives

Efficacy and Safety Assessments

Study Endpoints

Topics fitting the design pattern

Tabl

e of

Con

tent

s

class View: Genzyme SCM-Clinical Stu...

Protocol Representation Sub-Domain::Study{root}

+ accrualReportingMethodCode: CD+ acronym: ST+ aeCodingSystem: II+ designConfigurationCode: CD+ diseaseCode: DSET<CD>+ multiInsti tutionIndicator: BL+ participatingCountryCode: DSET<CD>+ participatingOrganizationTypeCode: CD+ periodicTargetAccrualNumber: RTO<INT,PQ>+ phaseCode: CD+ plannedStudySubjectExperience: ST+ populationDescription: ST+ primaryPurposeCode: CD+ purposeStatement: ST+ responsiblePartyCode: CD+ studySchematic: ED+ studySubjectTypeCode: CD+ targetAccrualNumberRange: URG<INT>+ targetAnatomicSiteCode: DSET<CD>

MaterialCommon Sub-Domain::Product

{leaf}

+ classCode: DSET<CD>+ expirationDate: TS.DATE.FULL+ nameCode: CD+ nameModifiedText: ST+ pre1938Indicator: BL+ treatmentVehicleCode: CD+ treatmentVehicleVolume: PQ+ typeCode: CD::Material+ actualIndicator: BL+ description: ST+ effectiveDateRange: IVL<TS.DATETIME>+ formCode: CD+ identifier: DSET<II>+ name: DSET<TN>

View of elements identified in the Genzyme SCM Information Architecture for product manufacture.

Adverse Event Sub-Domain

Common Sub-Domain

Protocol Representation Sub-Domain

Regulatory Sub-Domain

Study Conduct Sub-Domain

Genzyme SCM

Legend

Common Sub-Domain::Activity{root}

+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedActiv ity{leaf}

+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedAdministrativ eActiv ity{leaf}

::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedProcedure{leaf}

+ approachAnatomicSiteCode: CD+ methodCode: CD+ targetAnatomicSiteCode: CD+ targetAnatomicSiteConditionCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedObserv ation{leaf}

+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateral ityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identi fier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedEligibilityCriterion{leaf}

+ displayOrder: INT+ requiredResponse: ANY::DefinedObservation+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedImaging

{leaf}

+ contrastAgentEnhancementIndicator: BL+ enhancementDescription: ST+ enhancementRateValue: RTO<PQ, PQ.TIME>::DefinedObservation+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedStratificationCriterion

{leaf}

::DefinedObservation+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedInclusionCriterion

{leaf}

::DefinedEligibil ityCriterion+ displayOrder: INT+ requiredResponse: ANY::DefinedObservation+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::DefinedExclusionCriterion

{leaf}

::DefinedEligibil ityCriterion+ displayOrder: INT+ requiredResponse: ANY::DefinedObservation+ bodyPositionCode: CD+ derivationExpression: ST+ focalDateRange: EXPR<IVL<TS.DATETIME>>+ /focalDuration: PQ.TIME+ methodCode: DSET<CD>+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD::DefinedActivity+ categoryCode: CD+ description: ST+ nameCode: CD+ /repeatDuration: PQ.TIME+ repeatFrequencyCode: CD+ repeatFrequencyRatio: RTO<INT,PQ.TIME>+ repeatQuantity: INT+ statusCode: CD+ statusDate: TS.DATETIME+ subcategoryCode: CD::Activity+ comment: ST+ identifier: II+ reasonCode: DSET<CD>

Protocol Representation Sub-Domain::StudyActiv ity

+ studyFocusIndicator: BL

Protocol Representation Sub-Domain::StudyAgent

+ functionCode: CD+ statusCode: CD+ statusDate: TS.DATETIME Protocol Representation Sub-Domain::

StudyProtocolDocument{leaf}

+ publicDescription: ST+ publicTitle: ST+ scientificDescription: ST::Document+ bibliographicDesignation: ST+ keywordCode: DSET<CD>+ keywordText: DSET<ST>+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ text: ED+ typeCode: CD+ uniformResourceLocator: URL

Common Sub-Domain::Document{root}

+ bibliographicDesignation: ST+ keywordCode: DSET<CD>+ keywordText: DSET<ST>+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ text: ED+ typeCode: CD+ uniformResourceLocator: URL

Common Sub-Domain::DocumentIdentifier

+ identifier: II+ primaryIndicator: BL+ typeCode: CD

Common Sub-Domain::DocumentAuthor{root}

Genzyme SCM Common Sub-Domain::Topic{root}

+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

Common Sub-Domain::DocumentRelationship

+ typeCode: CD

Genzyme SCM Common Sub-Domain::TopicMap

+ officialTitle: ST+ topicRelataionshipReference: TopicMapCompositionRelationship+ uniformResourceIdentifier: ST

Genzyme SCM Common Sub-Domain::

TopicMapCompositionRelationship

+ comment: ST+ sequenceNumber: int+ sourceTopicMapReference: ST+ targetTopicMapReference: ST+ uniformResourceIdentifier: ST

Common Sub-Domain::Drug{leaf}

+ lotNumberText: ST::Product+ classCode: DSET<CD>+ expirationDate: TS.DATE.FULL+ nameCode: CD+ nameModifiedText: ST+ pre1938Indicator: BL+ treatmentVehicleCode: CD+ treatmentVehicleVolume: PQ+ typeCode: CD::Material+ actualIndicator: BL+ description: ST+ effectiveDateRange: IVL<TS.DATETIME>+ formCode: CD+ identifier: DSET<II>+ name: DSET<TN>

Protocol Representation Sub-Domain::StudyObjectiv e

+ description: ST+ primaryIndicator: BL

Protocol Representation Sub-Domain::

StudyOutcomeMeasure

+ name: ST+ primaryIndicator: BL+ timeFrameText: ST+ typeCode: DSET<CD>

Protocol Representation Sub-Domain::StudyReference

+ citationDescription: ST+ linkPageDescription: ST+ publicationIdentifier: II+ publicationName: ST+ universalResourceLocator: URL

Common Sub-Domain::Report{leaf}

+ communicationModeCode: CD::Document+ bibliographicDesignation: ST+ keywordCode: DSET<CD>+ keywordText: DSET<ST>+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ text: ED+ typeCode: CD+ uniformResourceLocator: URL

Adv erse Ev ent Sub-Domain::SafetyReport{leaf}

+ nulli ficationIndicator: BL+ nulli ficationReasonCode: CD+ subtypeCode: CD::Report+ communicationModeCode: CD::Document+ bibliographicDesignation: ST+ keywordCode: DSET<CD>+ keywordText: DSET<ST>+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ text: ED+ typeCode: CD+ uniformResourceLocator: URL

Common Sub-Domain::Biologic{leaf}

+ lotNumberText: ST::Product+ classCode: DSET<CD>+ expirationDate: TS.DATE.FULL+ nameCode: CD+ nameModifiedText: ST+ pre1938Indicator: BL+ treatmentVehicleCode: CD+ treatmentVehicleVolume: PQ+ typeCode: CD::Material+ actualIndicator: BL+ description: ST+ effectiveDateRange: IVL<TS.DATETIME>+ formCode: CD+ identifier: DSET<II>+ name: DSET<TN>

Study Conduct Sub-Domain::StudySite

+ accrualStatusCode: CD+ accrualStatusDate: TS.DATETIME+ dateRange: IVL<TS.DATETIME>+ identifier: II+ leadIndicator: BL+ statusCode: CD+ statusDate: TS.DATETIME+ targetAccrualNumberRange: URG<INT>

Genzyme SCM Common Sub-Domain::TopicSection

+ content: ST+ contentFormat: ST+ sequenceNumber: int+ title: ST+ uniformResourceIdenifier: ST

StudyDesignTopic{leaf}

- studyIntent: ST+ studyPhase: ST::Topic+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

StudyTopic{leaf}

+ dossageForm: ST+ dossageStrength: ST+ genericName: ST+ indication: ST+ routeOfAdmin: ST+ studyIdentifier: ST+ studyPhase: ST+ typeOfControl: ST::Topic+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialTi tle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

StudyConductTopic{leaf}

+ studyPhase: ST::Topic+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialT itle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

Genzyme SCM Common Sub-Domain::ProductTopic

{leaf}

+ genericName: ST+ indication: ST::Topic+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

For implementation, it may be more efficient to address Topic sub-classes as an enumeration of the Topic class.

+performed 0..*

is a function performed by

{functionsas}

+performing 1

+evaluated

0..*

is evaluated by

{isevaluating}

+evaluating

1

+associating 0..*

associates a study to

{isassociatedto a studyby}+associated 1

+associating 0..*

associates an activity to

{isassociatedto anactivity by}

+associated 1

+instantiating

0..*

is the execution of

{istheplanfor}

+instantiated

1

associates a Topic to a DefinedObservation

+identi fying

0..*

identifies

{is identified by}

+identified

1

associates a Topic to a DefinedProcedure

+using 0..*

uses

{isusedduring}

+used 0..*

associates a Topic to an AdministrativeActivity

associates a Topic to a Product

associates a Topic to a Study

+referencing

1..*

refers to

{is referenced by}

+referenced

0..*

+involved 1..*

is an aim of

{aims to achieve}

+involving 1

+is an instance of a single Section with a title and content

associates a TopicSection as part of a Topic

+is a collection of TopicSections

associates a Topic to a StudySite

+executing 0..*

executes

{is executed at}

+executes 1

+measuring

1..*

measures

{is measured by}

+measured

1..*

+is publication of Topics has a publication+provides ordered listof Topics

+is type of relationshiprelated TopicMap

+is source TopicMap

+provides an ordered list of Topics

associates a TopicMap to a Report

+is a publication of Topics

+is collection ofhas component

+is component of

+target

0..*

has as source

{is thesourcefor}

+source

1

+source

0..*

has as target

{is thetargetfor}

+target

1

associates a Topic to a CompositeRelationship object

+authoring

1..*

authors

{is authored by}

+authored

1

Name:Package:Version:Author:

View: Genzyme SCM-Clinical StudyGenzyme SCM Clinical Study Sub-Domain1.0Genzyme SCM

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Genzyme-BRIDG Structured Content Extensions


Adverse Event Sub-Domain

Common Sub-Domain

Protocol Representation Sub-Domain

Regulatory Sub-Domain

Study Conduct Sub-Domain

Genzyme SCM

Legend

SCM Structured Content Extensions

SCM Structured Content Extensions

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Rationale in Extending the BRIDG Model class View: Genzyme SCM-Clinical Stu...

Common Sub-Domain::Document{root}

+ bibliographicDesignation: ST+ keywordCode: DSET<CD>+ keywordText: DSET<ST>+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ text: ED+ typeCode: CD+ uniformResourceLocator: URL


Genzyme SCM Common Sub-Domain::TopicMap

+ officialTitle: ST+ topicRelataionshipReference: TopicMapCompositionRelationship+ uniformResourceIdentifier: ST


Genzyme SCM Common Sub-Domain::

TopicMapCompositionRelationship

+ comment: ST+ sequenceNumber: int+ sourceTopicMapReference: ST+ targetTopicMapReference: ST+ uniformResourceIdentifier: ST


Genzyme SCM Common Sub-Domain::Topic{root}

+ artifactName: ST+ businessProcess: ST+ businessUnit: ST+ contentType: ST+ domainName: ST+ market: ST+ officialTitle: ST+ revisionNumberText: ST+ revisionReason: ST+ section: TopicSection+ uniformResourceIdentifier: ST

1) One TopicMap is published to create One Document1) One TopicMap is published to create One Document

2) Each Topic has a relationship to one or more TopicMaps2) Each Topic has a relationship to one or more TopicMaps

StudyTopic

…

StudyDesignTopic

…

StudyConductTopic

…

ProductTopic

…

4) Sub-class Topics represent specific domains with respect to metadata

4) Sub-class Topics represent specific domains with respect to metadata

3) The “Topic” is the primary unit of reusable content

3) The “Topic” is the primary unit of reusable content

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A Standard Mapping Table (BRIDG PRM)

CORE BRIDG Description Applied ToArtifact: Study Legal Sponsor Title: <name of organization>Property: Name Domain: Clinical Study-Sponsor ContentType: Legal Entity Role: Instance Category: CORE

Class: StudyLegalSponsorAttribute: nameDomain: BRIDG DAM Protocol Representation Sub-Domain

The name of the clinical study sponsor

Property of a Topic

Artifact: Study Legal Sponsor Title: <name of organization>Property: Postal Address Domain: Clinical Study-Sponsor ContentType: Legal Entity Role: Instance Category: CORE

Class: StudyLegalSponsorAttribute: postalAddressDomain: BRIDG DAM Protocol Representation Sub-Domain

The postal address of the clinical study sponsor

Property of a Topic

Artifact: Standard Mapping TableTitle: Genzyme CORE To BRIDG MapDomain: Clinical StudyContentType: ConfigurationRole: InstanceSourceType: Word TableCategory: CORE

• A Standard Mapping Tableo is a Topic with CORE metadatao provides the information needed to translate

from the CORE content architecture to another data standard

• A Standard Mapping Tableo is a Topic with CORE metadatao provides the information needed to translate

from the CORE content architecture to another data standard

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Single Source of Content: Mapped to Multiple Data Standards

Topic(content)

• A single Topic can be represented by metadata from different standards• Each data standard can be thought of as “plugging” into the Topic like spokes on a wheel• A single Topic can be represented by metadata from different standards• Each data standard can be thought of as “plugging” into the Topic like spokes on a wheel

CDISC BRIDG PRMProtocol Representation Model

CDISC ODMOperational Data Model

HL7 CTR&R Clinical Trial Registration & Results Model

Genzyme CORE Content Architecture

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Metadata for Content and Data Alignment

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• Trial Arm(s) or “treatment regimen” are described in the content of the protocol• Content describing the “Placebo” trial arm determines the data in the Trial Arm Dataset• Content metadata for the “Placebo” trial arm aligns with metadata for the Trial Arm Dataset

Standard Attribute Value

Trial Arm Dataset(CDISC SDTM)

STUDYID AB123456

DOMAIN TA (Trial Arm)

ARM Placebo

ELEMENT Placebo

EPOCH Treatment

Attribute ValueArtifact Treatments Administered

Title Study Arm-Placebo

Domain Clinical Study-Dosing

Content Type Study Design

Content Level Metadata

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Metadata for Content and Data Alignment cont...

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• Assessment Topics from Protocol determine Schedule of Study Events• Schedule of Study Events determines clinical data collected (e.g., CRFs)

Attribute ValueArtifact Vital Signs

Title Blood Pressure/Pulse-Standing

Domain Vital Signs and Body Measurements

Content Type Clinical Assessment

Topic Metadata

Clinical ProtocolClinical Content

Objectives

Endpoints

Assessments

Inclusion / ExclusionCriteria

Study phase Screening TreatmentVisit Numbers Visit 1 Visit 2

Week Week -1 Week 2Screen

Inclusion/Exclusion criteria XMedical History XDemography XDosing, AEs and ConMedsDrug administration XSerious Adverse Events As requiredConcomitant meds/Therapies As requiredVital signsBlood pressure / Pulse rate X X

Case Report Form

Domain:

Position:

Diastolic BP:

Systolic BP:

Vital Signs

Standing

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Topic MapTopic MapReusable Topic PoolReusable Topic Pool

ClinicalTrials.gov XML Submission<?xml version="1.0" encoding="UTF-8"?><clinical_study rank="1">

<id_info><org_study_id> [Protocol Number]</org_study_id><nct_id>[NCTXXXXXXXXX]</nct_id></id_info><official_title>A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Assess the Safety and Efficacy of Thrice Weekly and Once Weekly Regimens of Mipomersen Sodium in Patients with Familial Hypercholesterolemia</official_title><sponsors><lead_sponsor><agency>Genzyme</agency><agency class>Industry</agency_class></lead_sponsor></sponsors><primary_outcome>

<measure> To compare percent change in LDL-C from Baseline to Week 28/Early Termination (ET represents the observation closest to 2 weeks after last dose among patients who early terminate study medication dosing)

</measure><time_frame>up to 2 years</time_frame><safety_issue>No</safety_issue>

</primary_outcome>

<intervention><intervention_type>Biological</intervention_type><intervention_name>[Name]</intervention_name><description>1 mg/kg, Day 1, Day 28, Day 56, and Day 84 patients will receive a single intravenous (IV)

[Investigational Product]</description><arm_group_label>Cohort A</arm_group_label>

</intervention>

titleStudy id

PrimaryPrimary

SecondarySecondary

endpointobjective

endpointobjective

Business documents published in format

Business documents published in format

ClinicalTrials.govXML Submission

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NOTE: Topics from the protocol can be published into XML such as that for a ClinicalTrials.gov XML submission.

NOTE: The topic map (aka the document) actually provides the context for an Objective or Endpoint being “Primary”, “Secondary” or “Exploratory”.

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Structured Document Walk Through

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Global Protocol Guidance

(PDF file)

• Guidance• Sample text• Example text

Provides authors with by section authoring guidance on protocol content

•Standard text

Mandatory language that reflects Genzyme’s “best practices”

Global Structured Protocol Template –A More Robust Starting Point

Global Protocol Template

Global Structured Protocol Template

(2003 .dot file)

• Standard formatting

Provides Genzyme-specific formatting and styles

+ =+

Content Repository

(.doc files)

• Reusable content

Appropriate protocol content is selected by Content Designer from repository

(2007 .dotm file)

• Guidance• Sample text• Example text• Instruction text• Standard text• Standard formatting

Draft Protocol v0.1

• Draft content

Starting point for protocol authoring

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Draft and Final Publication Filters

A document may be published for different purposes• DRAFT documents are designed to assist the author, reviewer(s) and other

contributors to understand what content should be• FINAL documents are meant for use by a document consumer

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Output Class

author

consumer

• Contains:• Guidance, Instructions,

Samples, Examples• DRAFT Content• Standard Text• Standard Formatting

• Contains:• Content (DRAFT or FINAL)• Standard Text• Standard Formatting

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Single Source Publishing

• Content published to Word can also be published to XML in a defined format

• The common DITA Topic content can be “published” to Word or other XML formats such as that required for Clinical Trial registration e.g., ClinicalTrials.gov, EudraCT, CTR&R HL7 message

Publ

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s* Content Selected for

CTT Registration

• ClinicalTrials.gov DTD• EudraCT DTD

Publish to Word

Publish to an XML

Topic

Topic

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Structured Document Walk Through

● Structured Protocol – “Baseline” Structured Protocol Template (published)– Sample Structured Protocol Document (v0.1)

● Opportunities Beyond the Traditional Protocol– Facilitate Meaningful Review of Protocol Content

• Structured Objectives, Endpoints, and Assessments Table – Automated Reuse of Protocol Content

• Structured CTT Protocol Registration Document

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Summary: Benefits of Topic-Based SCM & Metadata Enabled Processes● “Quality by Design”

– Content architecture: right information, right place• Objectives, Measures and Assessments

– Information standards • e.g., CDISC: BRIDG PRM, CDASH, SDTM, ODM• Controlled terminology/vocabularies

● Search: Finding the “right” information– Search at the topic level vs. document level

● Lifecycle Management– Change control– Governance

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Achieving efficiency by bringing global business process and technology together through standards

Thank You!

Questions/comments, please feel free to contact:A. Brooke Hinkson ([email protected])Angela M. Horowitz ([email protected])

Acknowledgement:A special thank you to Jim Averback for his invaluable contribution to our topic-based SCM initiative!