# Presentation: 252766

##  CTMS November 2006 Face-to-Face Welcome and Progress November 27, 2006

***Meg Gronvall***
***John Speakman***
***Christo Andonyadis***

## Agenda

- Welcome and Introductions
- CTMS Progress
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
- CTMS Program Management
- CTMS Strategic Next Steps

## Agenda

**Welcome and Introductions **
**CTMS Progress**
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
**CTMS Program Management**
**CTMS Strategic Next Steps**

## CTMS Core Team

**NCICB**
- John Speakman, *Associate Director, Clinical Trials Products and Programs; Workspace Lead*
- Christo Andonyadis, *Associate Director, Clinical Trials Application Engineering*
**BAH**
- Meg Gronvall, *Workspace Lead*
- Charlie Mead, *Technical Lead*
- Julie Holtzople, *Delivery Management*

## Agenda

**Welcome and Introductions **
**CTMS Progress**
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
**CTMS Program Management**
**CTMS Strategic Next Steps**

## What John has learned since moving to NCICB

- For every conference call caBIGTM has, we have three
- The reason that things sometimes move very slowly isn’t that there’s a conspiracy to hide stuff - in fact the opposite is true
- So... if you feel that there’s something in CTMS that hasn’t been communicated to you, or something doesn’t sound right, don’t just complain to each other, let us know!

## John Speakman, NCICB

**E-mail:**** ****john.speakman@nih.gov**
**Cell phone:**
**	****301 256 7342**
**Office:**
**	****301 451 8786**

## Clinical Trials Management Workspace Goals, Circa 2004

- Improve clinical research productivity
- Integrate the clinical trials infrastructure with the research infrastructure
- Allow sharing of de-identified data across trials and sites
- Facilitate greater standardization of coding, vocabulary, nomenclature and data collection methods as part of clinical trials
- Define specifications to be followed by developers of new or existing clinical trials systems intended to be compatible with caBIG
- Consistency with NIH Roadmap direction

*caBIG – Applications Overview*, S. Dubman, February 19, 2004

## Nixon’s “War on Cancer” and the Clinton-era doubling of the NIH budget enabled us to  figure out“How Cancer Works” (Lauren Sompayrac)but we cannot deliver the full fruits of this knowledge to patients

**Our Delivery Challenge**

## Enabling Translational Research

**Time**

**Information**

*(from Robert C. Bast, Jr., MD)*

## February 2004 CTMS Prioritization

**List of Community Needs**
***CDUS/CTMS reporting***
***Adverse event reporting***
***Laboratory interface module***
***Financial and billing system***
**Reporting to the FDA, IND Holder, and hospitals**
**Automatic grading of toxicities for CTC**
**Support multiple destination formats for reporting**
**Protocol management**
**Data conversion tools**
**Patient eligibility filtering and tracking**
**Patient matching to clinical trials**
**Systematic lay summaries**
**Investigator registry**
**Outcomes assessment**
**Participant registry**
**Summary 4 reporting**

## Current CTMS SIGs

**  ****CTMS WS**

**CTMS Steering Committee**

**Adverse Event  Reporting**

**Study Calendar**

**Routine  Data  Exchange**

**Financial Billing**

**Structured **
**Protocol Representation**

**Laboratory        Interfaces**

**Best Practices**

**Clinical Trials Database**

**Systems**
**I/H**

**CRF **
**Standardization**

**Investigator**
**And**
**Site      Credentialing**

## CTMS Vision Statement (May 5, 2004)

- 	“...develop a comprehensive set of modular, interoperable and standards based tools designed to meet the diverse clinical trials management needs of the **Cancer Center community**. The tools developed will be configurable to meet the needs of Cancer Centers with little or no clinical data management systems in place as well as those with robust systems, and will take into account the diversity of clinical research activities and local practices that exist among these Cancer Centers. The caBIG core principles of open source, open access, open development and federation of data sources will guide all new tool and product development. In particular for this Workspace, **interoperability and modular development are key**, as solutions are likely to consist of a flexible assembly of compatible tools pulled from a rich collection of tools developed by the Workspace, as well as existing commercial and locally developed solutions that have been made caBIG compatible by the community.”

## Current Vision (up for discussion)

- Supporting a Broader Community
- Cooperative Groups, SPOREs, CCOPs, Cancer Centers
- Investigators, Data Managers, Statisticians
- An End-to-end Data Pipeline
- From Point-of-care Systems (Clinical and Scientific) through sponsor submission to regulatory submission
- A Modular Architecture
- Enabling rapid technological adaptation to new science
- Data Sharing Without Manual Intervention
- Common Data Elements
- Common APIs
- Robust yet flexible security system

**Notes:**
Technology to support discovery and agility

## “End-to-End”

- Inputs:
- caXchange (aka the Lab Hub) is a model for a flexible infrastructure that will allow **any** data source (clinical or otherwise) to supply clinical trials with data (*e.g.*, surgery, pathology, imaging, gene expression)
- Outputs:
- To enable new science through
- 	data mining
- To simplify submissions to sponsors
- 	(e.g., NCI, pharmaceutical
- 	companies, others)
- To streamline regulatory
- 	submission by sponsors (*e.g.,*
- 	from pharmaceutical companies
- 	to the FDA)

**Notes:**
What else do we care about???

## Adventures in Regulatory Submission

- Problems
- Time-intensive, paper-intensive, labor-intensive regulatory submission process
- Not just an FDA/pharma problem: This is slowing the delivery of innovative therapies to patients
- Approach: Inter-Agency Operational Task Force (IOTF)
- Solution: CRIX (Clinical Research Information eXchange)
- Facilitate adoption of electronic data standards, standardized terminologies, and electronic submissions
- Reduce the cost of information gathering,
- 	submissions and analysis / review
- Allow secure transmission/sharing of clinical
- 	research data

## FIREBIRD

- Automates/centralizes investigator registration and accreditation process (currently uses FDA Form 1572 – cumbersome, repetitive)
- Enables investigators
- 	to register online
- Digital signature
- 	technology
- Now in operational
- 	pilot with NCI, FDA,
- 	selected medical
- 	centers/investigators
- 	and selected
- 	pharma companies

## “Modular”

- NCI **does not** want to prescribe a single clinical trials software solution
- NCI **does** want to foster an infrastructure where everyone can take advantage of caBIGTM-developed software modules
- whether they buy, build, obtain
- 	an open source solution, etc.
- NCI **especially** wants to
- 	foster an infrastructure
- 	where **computable, semantically **
**     ****interoperable** data are easily shared
- NCI proposes a **modular**
- 	infrastructure to support
- 	cancer clinical trials as they
- 	adapt to changing science

## Getting There From Here

- Modular and interoperable is not how it works currently at Cancer Centers and Cooperative Groups
- Selecting a CTMS is an *enterprise-level* decision
- NCI’s job is to identify and build a long-term
- 	architecture that will support the
- 	changing needs of science
- If you’re buying or building, we’d like to
- 	work with you and/or your vendor
- Modular and interoperable is also not
- 	how it works currently within the NCI
- We expect CTWG to be a driving force

## CTMS: We have built a community

- Our immediate challenge is to *extend* the CTMS community to
- 	include more
- 	“trialists”:
- Investigators
- Community
- 	Oncologists
- Data
- 	Managers
- Statisticians

## Agenda

**Welcome and Introductions **
**CTMS Progress**
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
**CTMS Program Management**
**CTMS Strategic Next Steps**

## Clinical Trials Management Workspace, Circa July 2006

- RFPs
- Patient Study Calendar (Awarded & under development)
- Lab Hub Interface (Awarded & under development)
- Protocol Lifecycle Management (Under Evaluation)
- caAERS Release 1 Prototype: submitted and approved
- 7 Cancer Centers utilizing C3D infrastructure (Including 2 C3PR adopters)
- BRIDG Model:
- Used as modeling foundation for all CTMS development projects
- Adding the dynamic aspect (Best Practices/SOPs)

## Clinical Trials Management Workspace, Circa July 2006 (continued)

- Clinical Trial Reporting:
- CDS Pilot testing for Analysis and Reporting module and Protocol Abstraction
- Financial Billing
- Standard Operating Procedures:  18 Published SOPs, 8 awaiting approval
- CTWG
- Clinical Trials Data Base (CTDB) project: Launched
- Systems Interoperability & Harmonization (SIH) project:  Launched
- Study Initiation Tool (SIT) Project: Launched
- Case Report Forms (CRF) project:  Launched
- Investigator & Site Credentialing (ISC) project:  Planned launch in August 2006
- Expanded the Workspace from 7 SIGs to 11 SIGs

## caBIGTM CTMS Critical Path - 2006

## Clinical Trials Management Workspace, Circa November 2006

**CTMS Governance**
**Development Projects**
- Patient Study Calendar (December 2006 completion)
- Lab Hub Interface (caXchange) (December 2006 completion)
- Protocol Lifecycle Management (Inception Phase November 2006 completion)
**RFPs**
- C3PR Phase 2 (Awarded and under development)
- caAERS Phase 2 (Awarded and under development)
- Protocol Lifecycle Management Phase 2 (RFP is on the street)
**CTMS Interoperability Project (under development)**

## Clinical Trials Management Workspace, Circa November 2006 (continued)

**CTWG**
- Clinical Trials Data Base (CTDB) project (under development)
- Systems Interoperability & Harmonization (SIH) project (under development)
- Case Report Forms (CRF) project (under development)
- Investigator & Site Credentialing (ISC) project
- Study Initiation Tool (SIT) project
**7 Cancer Centers utilizing C3D infrastructure (Including 3 C3PR adopters)**
**BRIDG Model:  **
- Used as modeling foundation for all CTMS development projects
- Harmonized with caXchange and Study Calendar
- Planned: SDTM (December), C3PR, caAERS, PLT (Q12007)

## Clinical Trials Management Workspace, Circa November 2006 (continued)

**Clinical Trial Reporting:**
- CDS Pilot testing for Analysis and Reporting module and Protocol Abstraction
**Financial Billing**
**Standard Operating Procedures:  26 Published SOPs, 3 draft**

## Agenda

**Welcome and Introductions **
**CTMS Progress**
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
**CTMS Program Management**
**CTMS Strategic Next Steps**

## How do/will we manage all this ???

- Unified Process Framework
- Layered and cross-project Coordination and Management
- CTMS projects
- caBIGTM projects

## Program Management:  Unified Process Framework (UPF)

- Industry Best Practices for solving complex problems
- UPF Core Principles
- Multi-disciplinary project teams
- Clinical Research expertise, informatics expertise, leadership expertise
- Continuous, structured risk management of project risks
- Early identification of risks to project, formal mitigation/contingency plans
- Iterative/incremental product development
- Deliver increasingly functional prototypes early and often
- Focus on underlying architecture as pre-requisite for scalability and extensibility of initial product
- Assume constantly changing functionality

**Notes:**
UPF provides structure and flexibility – adaptable to different types of projects (ie., not just for software engineering projects)
Overarching Complex Problem - Each project is a piece of the problem resolution

Multi-Disciplinary Project Teams
Representation from various perspectives of the problem from the stakeholder community.  Examples include:
Domain Expertise (Principal Investigators, Data Managers, Study Coordinators)
Technical Expertise (Architects, Developers, Analysts, DBAs)
Management Expertise (Cancer Center Directors)

Continuous Structured Risk Management
	Likelihood of occurrence of a specific risk
	Impact of a risk on a given project’s schedule or budget or functionality
	Updated and reviewed every 1-2 weeks
	Risks classified as Internal or External
		Internal: in control of project team
		External: not under control of project team
	Risk Mitigation Strategies/Risk Contingency Plans
		Set of tasks assigned to single, accountable resource
		Accomplishable within 1 week (done/not done)
		Flow through to Project Plan
Iterative and Incremental
” ...a successive series of releases of increasing completeness, where ... most critical risks [are] addressed first.”  [An Introduction to the Rational Unified Process, Peter Eeles, Kelli Houston, Wojtek Kazaczynski].

Clinical Iterative and Incremental example:
A physician seeing a patient for a particular complaint will:  
Assess the patient, 
Define the patient’s problem, 
Develop a plan for intervention, 
Execute the Intervention Plan
Evaluate the results of the Intervention
END OF AN ITERATION 
Assess the patient based on the results of Iteration 1
(Refine the definition of)/Define the patient’s problem
.......  

## A Unified Process Framework

**Governance**
**Project Management**
**Stakeholder Management**** **
**Business Requirements**
**Requirements Analysis**
**Analysis**
**Design**
**Implementation**
**Business Testing**
**Performance Testing**
**Technical Architecture**
**Data Conversion**
**Transition**
**Operations and Support**

**Inception**

**Elaboration**

**Construction**

**Transition**

**Production / Support**

**Initial**

**Iterations**

**Milestones**

**Elab.**
**#1**

**Elab.**
**#2**

**Const.**
**#1**

**Const.**
**#2**

**Const.**
**#3**

**Tran.**
**#1**

**Tran.**
**#2**

**Prod.**
**#1**

**Prod.**
**#2**

**Phases**

**A Unified Process Framework**
***(Iterative, Incremental, Risk-Focused, Architecture-Centric)***

## Operational Model 

## Multiple contributing factors to complexity

- The combination of multiple vertical levels of organization and cross-organization processes– involving people or systems
- Problems occur at the ‘crossing points’
- Understanding:  syntax and semantics
- Politics:  responsibility and accountability
- Cumulative experience in industry, art, and (cognitive) science has repeatedly shown that the best way to deal with complexity is through abstraction, layering, and the use of standards.
- Disparate (unstructured) approaches to different processes lead to unorganized behavior

- Hierarchical
- Accountability

- Cross-organization Processes

**Notes:**
, from organizational structure and distributed responsibility to communication barriers created by non-structured vocabularies

## Agenda

**Welcome and Introductions **
**CTMS Progress**
- Where Have We Been And Where Do We Think We’re Going?
- Progress since July 2006
**CTMS Program Management**
**CTMS Strategic Next Steps**

## What is the CTMS 3-5 Year Plan?

- What are the highest priorities for CTMS in the next 3-5 years?
- Do we continue to build on the projects that are currently underway to add additional functionality?  Or do we add new projects? Or both?

## Summary & Next Steps

- Begin working under the new governance structure to support the coordination and direction of the workspace
- Impose Best Practices for managing complex problems and building complex solutions
- Unified Process Framework
- Layered Project Management
- Continue collaboration with the NCI research community to build consensus on priorities
- SIGs:
- Do the current SIGs align with CTMS priorities?
- Continue to focus on requirements
- Continue to leverage BRIDG in the context of requirements definition of specific solutions
- Test, vet and provide feedback on software that is being built for you – The NCI Research Community

## Summary & Next Steps (Continued)

- Expand the community to include:
- Cooperative Groups, Community Clinical Oncology Programs (CCOPs), Specialized Programs of Research Excellence (SPOREs), NCI Intramural and Extramural parties
-  Principle Investigators, Research Nurses, Study Coordinators and other “end users” from the NCI research community
- Encourage collaborative partnerships between academic and/or commercial organizations combining organizations with deep subject matter expertise with organizations that develop software following best practices in software engineering

## A