Capital Technology Information Services, Inc.

1. Disease Management InformaticsArchitecture Framework Capital Technology Information Services, Inc. Presented to

2. Table of Content • Disease management Informatics market, purpose and commitment – Slides 3 to 17 • Informatics framework, technologies, architects and processes – Slides 18 to 35 • Disease management informatics for the cancer program – Slides 36 to 55 • Disease management informatics for the HIV/AIDS program – Slides 56 to 68 • Disease management Informatics for the Heart Program – slides 69 to 73 • Disease management Informatics for business intelligence Program – slides 74 to 82 • Disease management Informatics for the International Program – slides 83 to 100 Click here Click here Click here Click here Click here Click here Click here

3. Solution to the Global Public Health Requirements with the use of End to End Health Informatics Framework

4. Disease Management Challenges Not Enough Awareness Dramatic Disease Growth Limited and Disparate Resources Fragmented Connectivity Incomplete Public Policy Incompatible Informatics Frameworks

5. Disease Management Informatics Priorities based on the Industry CIOs Under 1,000 employees Over 1,000 employees CIO Priorities for the year 2003 All Use IT to improve business (patient Safety) purpose 38.8% 38.5% 39.0% Developing strategies that increase (net revenue) ROI 35.9% 30.3% 39.6% Meeting the regulatory compliance and standards 29.6% 28.7% 30.2% Improve productivity and efficiencies (Reducing costs) 24.7% 18.0% 29.1% Improving security and privacy requirements 19.4% 22.1% 17.6% Ensuring major projects are completed on time and budget 17.6% 18.0% 15.9% Ensuring enterprise wide stakeholder connectivity 16.4% 18.9% 14.8% Developing proper organization framework 15.1% 14.8% 15.4% Helping the enterprise improve customer service 14.5% 17.2% 12.6% Identifying appropriate investment levels for technology 13.5% 13.9% 13.2% Increase capacity utilization 12.8% 18.0% 9.3% Other 0.7% 1.6% 0.0% Primary source - CIO Insight

6. Disease Management Challenges and Informatics Solutions and theprimarytool isinformation Value of CTIS = Good Clinical Informatics (GCI)

7. Disease Management Informatics Requirements • The Disease Management Informatics purpose is to improve the lives of patients by finding better ways to prevent, treat, control, cure and care for the disease. CTIS utilizing its IT capacity and builds GCI based Informatics solutions; and attempts to forge broad collaborations within the Health Industry stakeholders to effectively promote awareness, support patient care, support research, enable development of new drugs, support treatment, provide surveillance, participate in disease control and provides support for the patient care. • The mission critical elements of Disease Management Informatics are: • Safety for the Patients • Efficacy (and Effectiveness) of the Drug • Productivity of the People • Efficiencies of the Processes • Sustainability of the Applications • Reliability of the Information • Scalability of the Technologies • Collaboration between the Stakeholders

8. End to End Disease Management Process – Enabled Through Informatics Connect Control Cure Care Phase Connect the population to prevent the disease before it may happen Control the disease process in the population as it happens Provide the cure through treatment for the disease when it happens Provide care after the outcome for comfort and continuum Goal • Awareness • Promotion • Registration • Screening • Profiling • Assessment • Regimen • Research • Surveillance • Epidemiology • Oversight • Interventions • Patterns • Education • Therapy • Integration • Diagnostics • Protocol • Treatment • Drugs/Devices • Laboratory • Process • Collaboration • Results • Program • Connectivity • Comfort • Association • Reminders • Maintenance • Updates • Monitoring Activities • Genetic • Life style • Behavior • Social • Diet • Exercise • Spiritual • Therapeutic • Record Keeping • Participation • Communication • Collaboration • Practice • Alerts • Feedback • Vital signs • Preparation • Participation • Follow-through • Environment • Coordination • Event-management • Critical-path • Alignment • Family • Work-place • Community • Environment • Setting • Workflow • Sharing • Training Components

9. Disease Management Science Elements VBI Graphic

10. Disease Management Informatics Growth Bioinformatics Management Gene, Protein, Phenotype and Translational Data Management, Computational, Patterns, Pathways Clinical Management Phase II and III Protocol Trial Setup Trial Conduct Trial Tracking Trial Outcome Outcome Management FDA Approval Phase IV Market Phase Post Patent Discovery Management Design Phase In vivo and In vitro Pre-Clinical Early Discovery Medical Management Awareness, Prevention, Behavior and Social Treatment, Electronic Medical Record and Post Treatment

11. Expand the clinical informatics to end to end informatics through Bioinformatics - Research, development, or application of computational tools and approaches for expanding the use of biological, medical, clinical, behavioral or health data. where Genotype profile of tumor provides the probability of response; and genotype profiling of patient provides the probability of tolerance. From Giga to Terabytes – trillions of bytes of storage. Use Global IT networks for Integration. Integrate Computational capacity to add data mining for the data management Process - The development and application of data-analytical and theoretical methods, mathematical modeling and computational simulation techniques to the study of biological, behavioral, and social systems. Petaflops – of super computing power - thousands of trillions of floating points operations per second. Use global IT capacity for distributed super computing. Expand the human genome project alphabet to become the Disease Communication language. Develop the language that has right vocabulary and the ability to communicate. This will happen through computing power (SVMs) to build pattern recognition, pathways and phenotype traits; and Translation research. Use Global networks that speedup the process from bench to the bedside through the bridge of computing environment and optimized clinical trials process. Movement of a laboratory discovery into a patient or population research setting; and the movement of an observation in a patient or population setting into a laboratory research environment. Improve the health industry declining research productivity. The engine of growth in the industry remains innovation (new product discovery, design, development and deployment). To build a sustained and perpetual growth the industry needs to take full advantage of the new technologies that is driving drug delivery (i.e., genomic, proteomics one side and information technology on the other). The industry should leverage Global capability by structuring themselves around specific diseases and families of molecular targets; and maintain compliance with regulatory imperatives and engineer optimization with complex economic framework. Build end to end informatics from the beginning of the pipe (prevention) to the end of the pipe (care). Disease Management Informatics Strategy

12. CTIS Disease Management Legacy Platform 35 years - Information Outreach, Communication and Science 20 Years – Information Analysis, Decision Support and Business Intelligence 15 Years – Information Management and Infrastructure 10 Years – Disease Management Informatics

13. The total worldwide disease management informatics market in 2004 is estimated at over $40 billion with distribution between: discovery informatics ($5 billion), clinical informatics ($5 billion), bioinformatics ($15 billion), medial informatics ($10 billion) and decision support informatics ($5 billion) The overall market is growing at annual rate of over 15% with distribution between: discovery informatics (10%), clinical informatics (10%), bioinformatics (25%), medial informatics (10%) and decision support informatics (10%). Disease Management Market

14. Disease Management Market customers and needed services Industries: • National Institute of Health and disease specific institutes • Academic medical Institutes, Hospital and disease centers • Biotech, genomic and proteomic organizations • Pharmaceutical corporations • Contract research organizations and site management organizations • Life science consulting and IT companies • Agricultural business and sciences companies • Non-profit institutions and associations Informatics requirements: Building of the data warehouse with application, enterprise integration & web services layers; and providing end to end information tracking and exchange with specific functions such as: • Source and acquire information; and perform information curation • Extract and Integrate the information; and validate information integrity • Handle and manage information; and optimize information workflow • Comply with regulatory requirements; and meet information standards • Build repositories with information assurance; and provide information security • Develop information applications; and deliver information reporting • Provide High performance computing; and build information pattern recognition • Analyze and communicate information; and connect information stakeholders • Publish & Interchange information; and enhance information collaboration • Mine information & develop business intelligence; and provide information decision support

15. NIH Roadmap plans to support through informatics the requirements of important challenges in biomedical research to include: • Integration of clinical research networks • Integrating critical insights relating to genomics, proteomics, other biomarkers and prognostic indicators into the clinical research process • Development of enabling technologies for improved assessment of clinical outcomes • Harmonization of clinical research regulatory processes NIH Disease Management Strategy CTIS is committed to creating informatics tools and optimized processes for moving biomedical discoveries rapidly from clinical testing into clinical practice.

16. Disease Management Opportunity Framework ICOG International DSS (Business Intelligence) Bio-Informatics (Computational) TrialBridge Development Framework NIAID/DAIDS HIV/AIDS NHLBI Heart Applications (Data Mgmt.) Connectivity (IT Network) Cancer NCI/CTEP Collaboration: Governmental, International, Institutes AMIs, Universities, Hospitals, Centers Networks, Community Organizations CROs, SMOs CTIS Business Platform: $150 million current backlog for the next five years. Expected to grow to $500 million in five years

17. Disease Management Priorities - CTIS Corporate Commitment Impact Strategy - The Use Of Informatics For Diseases Management Start with Chronic disease - Cancer, Heart, Diabetes, AIDS……….. Client (Patient) Focus - Underserved, Minority, developing world, Women & Children Training, Care, Support, Allegiance, Compassion, Respect…… Purpose Commitment - Highest Patient Safety And Most Drug Efficacy On demand, end to end, Integrity, workflow, compliance, security…… Product/Service Components - Total Solutions For All Stakeholders (Eight Tracks) Prevention, Registry, Epidemiology, Outreach, Control, Treatment, Trials, Research….. IT Solution Framework - Infrastructure, Transaction, Mgmt. And Intelligence Clinical, Regulatory, organization Development, Business Processes, HR Integration….. Technology Platform - Sustainable, Appropriate, Pervasive And Persuasive Scalable, interoperable, reliable, predictable, repeatable and Fault Tolerance…… Investment Value - Highest Return On Investment In Terms Of Human Value HR Productivity, Process Efficiency, Organization Effectiveness. Financial Engineering……… Service Delivery Requirements - On time, Cost Effective and Best Quality Standards, Performance, Tools, Change Management, QASP based……. Information Availability - On demand, as required and as necessary Anytime, Any place, through any device and in any environment…….

18. End to End Health Informatics Framework Technology, Solution and Architectural Processes

19. Build the Business Model based on Reuse mechanisms Build the Architectural Framework on Universal Processes Enhance Continuously Engineer and Optimize Process for Enhancements Disease Management Sustainability Paradigm

20. Disease Management Informatics Solution building - Six Elements Why “information” will enable disease management process FEAF RUP ZACHMAN Purpose What are the program logistics in the management of the “information” Compliance Product Plan How is the Information Transformed to knowledge and Knowhow Standards-GCP Critical Path Integrity Performance-AQL Value-KPA Tools-eEnable Platform-SOP Reliability Infrastructure-IA Productivity Security People Process Who are the stakeholders that will be the custodian of the Information How is the information collected, managed and communicated Practice Where and When the information environment is Managed and maintained

21. Disease Management Products ad Services Standards Framework IT Standards Data Standards IT Standards Data Standards Trial Bridge NASA/OMB ISO/CMM SDLC/FEED RUP/ZACHMAN MedDRA SnoMed ICD CTC Good Clinical Informatics Practice Standards Protection Standards Protection Standards Practice Standards Clinical Standards HIPAA 508 IA – Assurance EM - Recovery GPRA FEAF SIX SIGMA BEST PRACTICE Clinical Standards GCP/ICH CFR CDISC HL7

22. Disease Management Informatics Development Approach Process Disciplines Supporting Workflow RUP Methodology

23. What How Where Who When Why Disease Management Informatics Development Approach Zachman Framework

24. Disease Management Informatics Development Approach

25. Data Methods Processes DMI Good Clinical Informatics Framework • GCI is a convergence of GCP and CTRM informatics where the basic data transforms into good clinical information by providing: • Data curation and integrity at the data collection step, • Business rules integration and the processes connectivity at transaction management step, • Regulatory compliances and organization workflow at the application reporting step, and • Information security and privacy at the solution delivery step.

26. Disease Management Informatics Generic Components Clinical Information Services Relational Database Standards Services Portal Explorer Page Builder Multi - Dimensional Application Services Sub - Portal Builder Database Publishing Security Organization Services Flat File System Custom Hooks APIs Logic Collaboration Services Web Sites Infrastructure Services Foundation Server Data Sources

27. REQUEST RESULT Disease Management Architectural Framework Application Enterprise Global

28. Disease Management Architectural Layers

29. Y3 Y2 Y1 X1 X2 X3 DIM Z1 Z2 Z3 Z axis DIM Application Framework (DAF) The break down of any component, areas, processes or functions into 3 key areas Document Management Enterprise wide document management Y1 – Application Document Management Y2 – DW Document and Process Management Y3 – Stakeholders Collaboration Management Y axis Content Management Overall content collaboration and management X1 – Target Application Data Management X2 – Enterprise Data warehousing Management X3 – Web Services (external) data sources Management X axis Environment Management Overall vitals and performance management Z1 – Reference/Links and other connectivity Management Z2 – Standards, sources and other Interfaces Management Z3 – Audit and Performance (Values) Framework Management Capital Technology Information Services, Inc.

30. http://www.ctisinc.com Disease Management Digital Dash Board Framework

31. e-Track Disease Management Informatics Project Management workflow Client SM Client PO CTIS PD CTIS PM CTIS PLs

32. Disease Management Reuse Framework Reuse Organization Framework Sponsors National Institute 25% 50% Reuse Knowledge Management Process Reuse Infrastructure Platform Reuse Development Approach Methods RUP Reuse Program Structure Disease Segment Clinical Trials Reuse Program Processes Reuse Components Library 25% 35% Reuse Work Product Knowledge Working Applications Adverse Events

33. Reuse & Replicate Disease Management Informatics Focus Guiding Principles Train & Transfer Connect & Collaborate Research &Translate

34. TrialBridgeTM

35. Security / Privacy / Authentication Adapter Data Mining/Reporting Compliance Monitoring Forecasting Trends Business Intelligence Vital Sign Monitoring Raw Data Analyses Data Downloads Decision Support Intelligence Knowledge Information Raw Data Trial Bridge GCI VALIDATION LAYER “Four-Stage Data Scrubber” GCITM Technology Regulatory Compliance FDA NIH IRB Workflow & Critical Path Clinical & Scientific Integrity Data Security & Privacy TrialBridgeTM GCI Process and Coding Verification Trial BridgeTM Front End • Client-Customized Transactional Component Assembly • Off-the-Shelf Integration • Clinical References, Libraries INPUTS WORKFLOW & COMMUNICATION OUTPUTS Data uploads Direct data entry Electronic data capture Wireless electronic data capture Business process tools Guided regulatory compliance Document Management Scheduling Alerts Workflow Management Communication and Collaboration

36. Disease Management – Cancer Program Clinical Trial Research and Management Informatics – Cancer Program

37. Cancer Informatics Foundation – Significant CTEP/NCI experience Business Profile • Over 15 years with NCI • Over $100 million performed business • Over 100 professionals with current expertise • Over 1,000 years of direct experience • Over six years in future contracts • Over $75 million in business backlog • Over 15 departments and branches connectivity • Over 50 cancer centers connectivity • Over 15 Pharma companies connectivity • Technical Profile • End to End Clinical Trial Research and Management Informatics – 15 years • Full service communication and outreach support – 15 years • Web sites, portals and web services support – 10 years • Business Intelligence Informatics support – 5 years • Regulatory Compliance Informatics support – 10 years • Information assurance and CIT support – 10 years • Systems Integration and Enterprise Application Integration Support – 5 years.

38. Cancer Disease Management Program – National Cancer Institute

39. Cancer Informatics Foundation – Over 10 year CTEP/NCI experience Cancer Therapy Evaluation Program (CTEP) Initiative at National Cancer Institute (NCI) Organizational Profile • Considered world’s largest “pharmaceutical company” and clinical trials sponsor • Cancer Therapy Evaluation Program (CTEP) consists of 15 clinical trials Applications. • Tracking of Protocols, Drugs, INDs, Sites, Patients, Treatment, SAEs, Regulations. • Encompass 150+ INDs, 2000+ protocols; 6,000+ sites, 50,000+ documents. • Connects 6000+ sites, 10,000+ physicians, 600,000+ patients Information • Data Warehouse size – Over 100 Giga bytes • Investment over $100 million • Results of System Implementation • Increased Drug discovery capacity by over 20% • Increased Administrative capacity by 25% per Administrator • Generated > 30% ROI

40. Cancer Informatics Foundation – Over 10 year CTEP/NCI experience Cancer Therapy Evaluation Program (CTEP) Initiative Performance History Government Agencies MetricBeforeToday Letter of Intent to Concept Review 45 days 10 days Concept Review to Protocol Receipt 300 days 30 days Protocol Receipt to Protocol Approval 75 days 40 days Protocol Approval to Protocol Activation 100+ days <30 days Days before patient data received 360+ days <30 days Accuracy of Patient Data <40% >99% Avg. days to generate report >2 weeks online, real-time # of adverse events reported ~1000 ~10,000 # days before adverse event received 10-45 days <3 days # of non-reportable adverse events received 880+ <100 * CTIS has developed the CTEP Cancer Trials Enterprise System (CTES) “My favorite thing about the Clinical Trials Enterprise System (CTES)* is that it allows the program staff to directly access mission critical information at their desktops. We can make sure our time is used to the best effect, so we’re not just busy, but efficient.” Dr. Michael Montello, Chief of the Protocol and Information Office Cancer Therapy Evaluation Program, National Cancer Institute

41. Drug Repository Agreements CTA, CRADAs Regulatory Management Pharmaceutical Relations Management SAE Reporting Grants Management Protocol Registration CTRM Medical Officer Administrative Management Clinical Site Monitoring Scientific Management Accrual Statistics Demographics CTEP Environment in 1997/98 - The “Leaky Pipe” Protocol Authorization

42. CTMB- AIS CDUS CTC WEB AdEERS CEP PATS DARTS SMARTS RABITS FIATS CTEP- EIS Metalayer CTEP Environment in 2002 onwards – an end-to-end Tracking System CTEP Business Enterprise CTEP - Enterprise Database

43. A Case Study: The CTEP Enterprise System CTES Applications Overview CTES applications are tracking and inventory systems that allow the sponsors and regulators to monitor, measure and manage the clinical trials process. The system supports CTEP’s mission critical equipment with specific emphasis on human subject safety requirements; and associated drug efficacy, data integrity, process efficiency and people productivity. The solutions is scalable and reliable and provides all necessary informatics support for data curation, regulatory compliance, treatment workflow and information assurance. The applications have been developed in two primary formats: Client-server applications – used solely by CTEP professional staff and their local extramural support staff Web-based applications – used primarily by extramural support staff (i.e., Cancer Cooperative Groups Consortia, Networks, etc.) and other Single Institutions (i.e. universities, hospitals, private practice offices, etc.) CTES Informatics

44. CTES Applications Areas CTES applications include: Address Maintenance Module (AMM) Address Query Module (AQM) Protocol Authorization and Tracking System (PATS) Enterprise Query Module (EQW) Drug Authorization and Review Tracking System (DARTS) Dose Regimen System (Dose-Reg) Common Toxicity Criteria Tool (CTC Tool) Clinical Data Update System (CDUS) Clinical Data Update Reports (CDU Reports) Adverse Event Expedited Reporting System (AdEERS) AdEERS Backend System (ABS) ABS-Do Not Process (ABS-DNP) CTEP-Enterprise Information System (CTEP-EIS) Enterprise Maintenance Module (EMS) Clinical Trials Monitoring Branch-Audit Information System (CTMB-AIS) Scientific Management of Agents Reporting and Tracking System (SMARTS) CTES Informatics

45. CTES Applications Overview: AdEERS Benefits (AdEERS & ABS) Streamlined the adverse event reporting process Helped to ensure adherence to clinical best practices and adverse event reporting guidelines Allowed for accurate data analysis that helps ensure patient safety Eliminated the need for the processing of Adverse Events that are assessed as not serious – resulted in a 40% reduction of reports that need immediate processing Helped reduce the number of unnecessary adverse event to less than 10% Key Features Processing Module – tracks the processing stages of the AE report Assessment – allows the assessment and reassessment of the adverse event data submitted by the investigator IDB DNP Module – facilitates reviewing and/or activating all AE report(s) Built-in security through the use of a key based mechanism consisting Standards-based including NCI’s Common Toxicity Criteria (CTC) and MedDRA Workflow-based Emailing alerts and notifications A built-in assessment module Allowing adverse event reporting for all trials CTES Informatics

46. CTES Applications Overview: CTMB-AIS Benefits Streamlined the clinical trials audit reporting process Helped to ensure adherence to clinical best practices and compliance with the federal code of regulations Allowed for accurate data analysis that helps ensure scheduling, performing, tracking and reporting audits. Eliminated the need for duplicate or organization specific audit process requirements Helped reduce the number of audit delays to less than 5% Key Features A web-based system to report clinical trial audit information to CTMB Allow electronically schedule audits, report audit findings, and submit roster updates Give online access to Roster and Audit data, maintain the audit schedule, and remind audits are due Provide regulatory reporting capability Provide role-based security at the database level CTES Informatics

47. CTES Applications Overview: CTEP-EIS Comprise the following tools: Enterprise Query Wizard (EQW) – enables users to gain immediate access to information. CTEP-Enterprise Information System (CTEP-EIS) – enables users to perform ad hoc queries, analyze data, and format query results Key Features Has exhaustive query criteria; & Allows for the design of custom reports based on criteria Assists in determining if a document exists in the database by accessing all data with specific criteria Permits electronic access to document for related documentation and correspondences Generating output of the query in Excel or PDF format Provide logical “All”, “Any”, and “NOT” functions for for query construction Provide: Customized drill down hierarchies Easy to understand Data filters Item classes (List of Values) Extensive graphical capabilities Focus primarily on three business areas: 1) Complete Document Information, 2) Protocol Accruals and 3) Toxicity An Online Analytical Processing (OLAP) tool Organized in the form of business areas and collection of folders Has pre-built report templates Allow end users to: Build new reports Share their reports with other users Save report on a central repository or a network drive Schedule complex and slow running reports at any off peak CTES Informatics

48. CTES Applications Overview: CTEP-EIS Benefits Enabled the implementation of new audit guidelines and procedures Eliminated data redundancy and discrepancy issues Allowed users to perform a variety of queries on demand and as necessary from anywhere Allowed users to run statistics and related graphical analysis Assured site compliance Ensured more efficient audit scheduling and reporting process Increased improvement in audit scheduling, reviewing and reporting efficiency Electronic access to documents and associated correspondences Reducing training costs Facilitate agent and disease development plans Number of help desk requests and queries for data reduced by over 25% Enhanced data quality and integrity Facilitate identification of bottlenecks and inefficiencies in the clinical trials process Enable data mining to support decision making Supports more INDs to go through the clinical trials process CTES Informatics

49. CTES Applications Overview: DARTS Key Features Standard Order Screen Special Exception Order screen Blinded Order Screen E-Loader Remote Order Entry System Benefits Increased in efficiency (2x drug requests and 4x blinded shipments) with no change in the level of effort Enabled NCI to support simple and complex blinded study designs and assures integrity of blinded studies Provided NCI with a full drug accountability from acquisition, receipt, and shipping to returns, transfers, and destructions Streamlined drug distribution procedures thereby reducing reduce distribution errors Promoted registration, management and tracking of over 10000 investigators to assure compliance with FDA policies Increase quality of data, streamline the workflow, and result in regulatory compliance Reduce PMB administrative efforts and reduce shipment errors Facilitated transfers and returns of drug, thereby reducing drug wastage Resulted in a quadrupling in the number of blinded shipments without any increase in administrative effort CTES Informatics

50. A Case Study: The CTEP Enterprise System CTES Applications Overview: PATS Key Features Document evaluation, creation and abstraction Document tracking and workflow Correspondence Module FDA Module Extensive Reporting Benefits Standardized the protocol abstraction process and eliminate data redundancies and need for multiple abstractions Improved data quality with over 400+ validations A 25% increase in the number of documents processed per year with no change in the level of effort Improved document processing and tracking Improved adherence to protocol development timelines by reducing administrative delays CTES Informatics