1 10/13/2015 8:25:15 pm cancer informatics infrastructure john silva, md national cancer institute...
TRANSCRIPT
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Cancer InformaticsCancer Informatics
InfrastructureInfrastructure
John Silva, MD
National Cancer Institute
Defense Advanced Research Projects Agency
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Problems with Clinical TrialsProblems with Clinical Trials
No systems Approach to Managing Continuum --> Discoveries into Routine Care
‘Eclectic’ Trials Data Not Patient Centered Record
No national-scale infrastructure to support trials or “Best Practices” for Cancer!
“Hassle Factors” for Both Patients and Physicians
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Creating the Clinical TrialCreating the Clinical Trial
InstitutionsInvestigators
CTEP
PDQ
Letter of Intent
CooperativeGroups
Clinical Trial
Public
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CRF
CRF
ReceiveCRFs
CaseReport Forms
Mail InFAX
Date/Time StampSegregate FormsCompleteness Checks
Complete?No
Yes
ReturnedDocument
InvestigatorComplete
Form
Return viaMail
DataReview
Match Study ParticipantVisual Screen for eligibility, correctness,consistency and versionLogged into Data CollectionCalendarForms still incomplete after 45 daysgenerate memo
Complete?No
Request forStudy Info
UpdatedCRFs
InvestigatorComplete
Form
Mail InFAX
Return viaMail
Today’s Paper ChaseToday’s Paper Chase
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Today’s StovepipesToday’s Stovepipes
High Risk High Risk LocalLocal Disseminated Disseminated Cancer
Spectrum
TechnologyBase
Prevention
Marker Studies Phase I-IIIEarly Detection
Adjuvant
Community
Cancer Centers
Cooperative Groups
Routine CareRoutine Care
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Real World ConstraintsReal World Constraints
“Legacy” Systems Dominate the Landscape
VERY Heterogeneous Data Environment
Data is Not Collected at Point of Creation
No Integration of Plans for Patient [clinical trial, protocol or critical path] with Processes of Care
Patients and Physicians Don’t Use Computers….
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Importance of the WEBImportance of the WEB
Number of Users Connected to the INTERNET
Electronic Power/Transportation Grid:
Fundamental Change in How Corporate America Works
Driving Rapid Development/Deployment of Information Technologies Electronic Commerce, Financial Services Have What we
Need
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Generation III. The Network Generation III. The Network EconomyEconomy
Retail
Financial Services Publishi
ng
Supply Chain
• Outsourcing
• Contract manufacturing
• Supply chain integration
• Open-source procurement
• Just-in time operations
• Virtual companiesCopyright © 1997 CNgroup. All Rights Reserved.
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Business OpportunitiesBusiness Opportunities
Shipping Banking
Trust
AggregatorInformation Intermediar
y
Supply Chain Management
AuctionsMatchmaker
Copyright © 1997 CNgroup. All Rights Reserved.
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Open framework for Open framework for commercecommerce
Mnfg HealthCare
Co
mp
uter
Au
tom
tive
Pin
nacles H
L/7
Supply Chain
eCo Frameworks
Appliances
Office
Co
nsu
mer
…Procure Retail
XM
L/ E
DIO
BI
OT
PSC
OR
OF
X
Copyright © 1997 CNgroup. All Rights Reserved.
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eCo FrameworkseCo Frameworks
eCo FrameworkseCo Frameworks
Business Forms
CatalogCatalog
Purchase OrderPurchase Order
InvoiceInvoice
Business Descriptions
VendorVendor
ServicesServices
ProductsProducts
Measurements
TimeTime
CurrencyCurrency
WeightWeight
Locale
AddressAddress
CountryCountry
LanguageLanguage
Classification
SICSIC
NAICSNAICS
FSCFSC
core
core
core
core
core
Copyright © 1997 CNgroup. All Rights Reserved.
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Interoperable RepositoriesInteroperable Repositories
University of CaliforniaSanta Barbara
“… not a bounded, uniform collection of information, but an open-ended collection of services” T. Winograd
Environmental & geographical information: •hardcopy & digital documents, •photographs & images, •maps, surveys, data,...
Multivalent documents
Tilebars
Image search
Map browser & Gazetteer
Catalog search
Texture search
Stanford University
Interoperability
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Clean CRF returned to repository
5
First Generation Uses of the First Generation Uses of the WEBWEB
User makesWeb Request to Enroll, File CRF, etc
1 Request interpreted from rules in repository.
2
®
Dynamic CRF created using specifications from repository
3Dynamic CRFis filled outby User
4
Trials Repository
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0
10,000
20,000
30,000
40,000
50,000
60,000
70,000
80,000
A (1989) B (1990) C (1991) D (1992) E (1993) F (1994)
Studies
Manual
Computerized Edit Checks
Edit Checks Available for Initial Data
Case Report Form Error RatesCase Report Form Error Rates
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Common ServicesCommon Services
Vision for the CII Vision for the CII
DiagnosticDiagnosticImagingImaging
Clinical TrialsClinical Trials
PatientPatientManagementManagement
SystemsSystems
PathologyPathology
BasicBasicResearchResearch
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Common ServicesCommon Services
Object ManagementObject Management–Control the process of storage, retrieval, of information Control the process of storage, retrieval, of information objectsobjects
Information BrokersInformation Brokers– Tools to find, filter, and process informationTools to find, filter, and process information
Discovery/Searching Discovery/Searching – Information clearinghousesInformation clearinghouses
Authentication and SecurityAuthentication and Security– Authentication, authorization, confidentiality, privacy, Authentication, authorization, confidentiality, privacy, integrityintegrity
Electronic PaymentsElectronic Payments– Digital money, payment orders, bartering systems, Digital money, payment orders, bartering systems, financial instrumentsfinancial instruments
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Digital RepositoriesDigital Repositories
National Information InfrastructureNational Information Infrastructure
Common ServicesCommon Services
DiagnosticDiagnosticImagingImaging
Clinical TrialsClinical Trials
PatientPatientManagementManagement
SystemsSystems
PathologyPathology
BasicBasicResearchResearch
Vision for the CII Vision for the CII
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PresentationLayer - Java - Visual Basic ***Components- EnterpriseJava Beans
Care Plan
Guideline
Patient
User
Report
Client
Object-By-ValueExternalization
or Proxies MiddleTierBusiness Objects
Middle Tiers
CORBASERVERS
ReportServer
DCOM
COM - CORBA
ODBCor Native
APIs
ODBC orNative
API Access
Server TierSystem Servers - DataServer - MetaServer - SessionServer - Collaboration Server ***
Database Servers - SQLServer - Oracle 8 - Sybase - ObjectStore ***
Java - CORBA
C++ - CORBA
Care Plan
Guideline
Patient
User
Business Objects & Components - CarePlan - Report - Guidelines - Tasks - Patient - Signs/Symptoms - User ***
N-Tier ArchitectureN-Tier Architecture
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SystemObject ServersDataServer, MetaServer, SessionServer,
CollaborationServer, ...
Business Objects: Patient, Guideline, Tasks,Reports, Protocols, Users, ...
EventService
TransactionService
NamingService
SecurityService
BusinessComponents &
Objects
CII Core ObjectFramework
Business Components: Encounters, Tasks, Protocols, ...
CII Workflow Service MetaServerCodeGenerator
CII ArchitectureCII Architecture
ActiveTrials
Repository
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Cancer ControlSecurity ServicesData Server
Trigger/Notif.Services
Map Services ProtocolServices
Schema/OntologyServices
Knowledge BaseServices
CollaborationServices
Common Common ServicesServices
Cancer SpectrumCancer Spectrum
LocalLocalLocalLocalAdvanced
Advanced
Advanced
AdvancedHigh Risk
High Risk
Unified Schema, Java Virtual Machine, Java Beans, CORBA Services, ...
Enterprise Object Services (OOWeb) - Persistence, Replication, Messaging, ...NationalNational
InfrastructureInfrastructure
StandardizedPatientRecord
&Case Report
Forms
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Next-Generation Clinical TrialNext-Generation Clinical Trial
• How Do We How Do We Disseminate Best Disseminate Best
Practices?Practices?
Active Trials
Repository
• Active Protocols • Local Data Sets• Local Protocols• Report Generators
• Literature• Active Trials• Trials Data Starter Kit• Event/Report Specs
Create
• Integrated into Care Processes & Systems• Reports Generated Using Local Systems
– CTEP– FDA– Groups– Payers/HCFA
UseUse
Diffuse
Diffuse
Accept
Accept
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Integrating Trials and Care Integrating Trials and Care
TrialsServer
CRF EditsConsistency
ReviewRequirem ents
ClinicalRecord
+CRF
Entry of datafrom Clinical
Sites ElectronicRequest forStudy Info
ClinicalData
Server
E lectron icT ransfer
TrialsRepository
S tandards
S tandards
Standards
CleanCRF
LAB
Imaging
Claims
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What We Are DoingWhat We Are Doing
Defining an Information Architecture for the “Trials Repository”
– Specifying How to Represent/Maintain/Use Objects within for the Trials Repository
– Providing the Distributed Object Services [EJB]– Enabling “Just What I Need” Information to Users
Protocol Authoring and Management– Electronic Work Flow and Document Management– Electronic Protocol Generation (Drag and Drop Authoring)
Pilot Sites to Test Models in “Real World”
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Creating “LEGO BLOCKS”Creating “LEGO BLOCKS”
Logical Data Models
Process Models
ActiveTrials
Repository
Applications Information & Object Services
Web
Client
Check Credit Check StockReserve StockRaise POConfirm Ship
Data StandardsBuilding Blocks
Task Hierarchies
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Model Reusability - IMPAC IIModel Reusability - IMPAC II
IMPACII EFDB GAB RAEB
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Auto Generate Objects Into Auto Generate Objects Into Framework of Common Framework of Common
ServicesServices
EventsCORBA / IIOP
TransactionsPersistence State
Security
DB Aware
Protocol Repository
Protocol
Objects
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Domain ModelDomain Modeltoto
Domain Reference ArchitectureDomain Reference Architecturetoto
MetaServerMetaServer
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Domain Engineering for Domain Engineering for ReUseReUse
Generate Use Cases
Verify Requirements
Perspective-based
Domain Model
Identify Subsystems
Identify Object
Classes
Specify OOD Model
Identify Class Dependencies
& Subsystems
ROSE
RARE
HyDRA and Views
Reports and
Knowledge Models
ROSEHuman
Note: Domain Architecture describes Object Classes and Subsystem. Domain Architecture consists of implementation-independent Classes. Each class is described by Declarative, Behavioral and Integration Models.
Evaluate Classes for coupling,
encapsulation, extensibility, etc.
Domain ArchitectureRepository
Technology Registration
Technology Capabilities &
System Configuration
Evaluation
D2K
Logical Models
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Code Generator
BWD System CompositionBWD System Composition
User Installation
#1Level of effort: 1) user populates installation infrastructure constraints, 2) select DRACS appropriate for user installation, 3) evaluate configurations of technology implementations of DRACS
DRAC
Technology Solutions registered against appropriate DRACs based on 1) domain reqmts technology satisfies and 2) app reqmts associated with installation infrastructure reqmts
DRACDRAC
DRAC
DRACDRAC
Selected Configuration
System Installation
MetaServer
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Auto Generate Object Auto Generate Object Connections to Data Sources Connections to Data Sources
From RepositoryFrom Repository
EventsCORBA / IIOP
TransactionsPersistence State
Security
DB AwareObjects w/
Defined Behaviors
OracleServer
SybaseServer
InformixServer
OOdatabases
Server TOFMXXXX
TOFMXXXX
TOFMXXXX
Text, Imagery,Web, Video Sources
Java Enhanced Data Server
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Power of an ApproachPower of an Approach
Logical Data Models
ProtocolModels
Clinical and Trials Applications
Web
DistributedActive
RepositoriesData Definitions
Building Blocks
Client
Check Credit Check StockReserve StockRaise POConfirm Ship
EventsCORBA / IIOP
TransactionsPersistence State
Security
DB AwareProtocol
Objects
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Protocol Management ToolsProtocol Management Tools
Protocol Repository
Investigators can author protocols
• Physicians can search for appropriate protocols
• Distribute protocols over the Network
Track general status of protocols during development & execution
Document management system for protocol review
Review status of a protocol graphically
EventsCORBA / IIOP
TransactionsPersistence State
Security
DB AwareProtocol
Objects
Protocol Use& Outcomes
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Clinical Trial “Building Blocks”Clinical Trial “Building Blocks”
Disease Monitoring End Results EfficacyEfficacy
CTC AER ... SafetySafety
EligibilityEligibilityClinical State Specific
ScientificQuestion
ScientificQuestion
DesignHypotheses Analyses
Informed ConsentInformed ConsentBenefit Safety
Drugs Schedule SchemaSchemaTreatments
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Logical View of Common Data Element Logical View of Common Data Element ModelModel
CDEModel
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Modeling CRFs Modeling CRFs
Treatment Case Report Forms (Groups and Industry)
Integrated Clinical Trial Case Report Form Model for Treatments
CTC
Reporting Requirements[Clinical Data Update (CDU), AER,
Common Toxicity Criteria (CTC), FDA, National Standards, HL-7]
Analyze and Architect
Data Elementsto Collect
EligibilityCDU
CDU
AERContains rules for all edits and consistency/logicalchecking for the CRFs
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Results of Eligibility Results of Eligibility Analysis MeetingAnalysis Meeting
Eligibility Framework– Tumor Characteristics [T, N. M]– Prior Treatments– Patient Characteristics– Initial Lab Data
Consolidated criteria into Clinical Concepts:
Histologically documented adenocarcinoma of the breastHistologically confirmed adenocarcinoma of the breastHistologically documented diagnosis of mammary adenocarcinoma with evidence of recurrent or metastatic diseaseHistologically documented mammary adenocarcinomaDiagnosed primary invasive adenocarcinoma of the breastHistologically confirmed diagnosis of breast cancerOperable, invasive primary breast cancerDiagnosed primary invasive adenocarcinoma of breast
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From Models to Clinical Trials From Models to Clinical Trials
CTC AER ...
Disease Monitoring End Results EfficacyEfficacy
SafetySafety
EligibilityEligibilityClinical State Specific
ScientificQuestions
ScientificQuestions
DesignHypotheses Analyses
Informed ConsentInformed ConsentBenefit Safety
Drugs Schedule SchemaSchemaTreatments
CTC
Clinical State
AER
Eligibility
Drug
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UMLUMLClass DiagramClass Diagram
End Results
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M Status?M Status?
1111
1212
1313
NoBreast Cancer?Breast Cancer?
11 22
Low HighDCIS
Yes
0 1 PriorTreatment?
PriorTreatment?
NoneER- or
hormoneUnresponsive
Chemo
Yes
Resectable?Resectable?
99
1010Number of
Nodes?Number of
Nodes?
66 77 88
T2, G2-3 T3
10 or more
Node NegativeNode Negative
44 55
1-30
T1, G1 T1,G2-3T2, G1
Clinical StatesClinical States
No
N 1-3N 1-3N 4-9N 4-9
Risk?Risk?
T1-2
4-9
T3 T3
Stage I Stage IIa Stage IIb Stage IIIa Stage IIIb
Stage IIIb
Stage IIIb
HR PosHR Pos
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Protocol Management ToolsProtocol Management Tools
Trials Repository
Investigators can author protocols
• Document management system for protocols
• Distribute protocols over the Network
Track general status of protocols during development & execution
Review status of a protocol graphically
Protocol Use& Outcomes
•Patient Records•Generated Case Report Forms• Patient Summary Records
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Automated Eligibility Automated Eligibility CheckingChecking
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Eligibility Checking Eligibility Checking “Method”“Method”
• Map patient attributes onto trials (Data Server)• For potentially eligible patients, generate OQL
patient data pulls via Data Server• OQL specifications for each trial from Protégé
representation stored ??• Evaluate patient against trials• Request additional data • Enroll patient