# Presentation: 735562

## Clinical Trials Management Systems (CTMS)Workspace

***Newcomers Session***

- Meg Gronvall, CTMS Workspace Lead
- Booz Allen Hamilton
**February 5, 2007**

## Agenda

**CTMS Team Introductions**
**What do we do?**
**How are we organized?**
**It’s been a busy year in CTMS: Progress Report and Pilot Products**

## Agenda

**CTMS Team Introductions**
**What do we do?**
**How are we organized?**
**It’s been a busy year in CTMS: Progress Report and Pilot Products**

## Who’s running CTMS?

**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

**CTMS Team Introductions**
**What do we do?**
**How are we organized?**
**It’s been a busy year in CTMS: Progress Report and Pilot Products**

## What do we do?Our Mission

**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

## “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)

## “Modular”

**The CTMS WS **does not** want to prescribe a single clinical trials software solution**
- 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.
- Especially** wants to**
**	****foster an infrastructure**
**	****where **computable, semantically
-      interoperable** data are easily shared**
**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
**The caBIGTM program strives 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
**CTMS is following an approach to design **
**	****and build computable, semantically, interoperable**
**	****modules**
**We expect CTWG to be a driving force**

## Four related Clinical Trial Working Group (CTWG) informatics-based initiatives

- Establish a comprehensive database containing regularly-updated information on all NCI-funded clinical trials
***	******Clinical Trials Database***** ***** ***
- Promote the establishment of a National Clinical Trial Information Technology Infrastructure that is fully interoperable with NCI’s caBIGTM Program
- 	***Systems Interoperability & Harmonization***
- Develop standard case report forms (CRF) that incorporate common data elements (CDE).  This initiative will be done in consultation with industry and the FDA.
***	******Case Report Forms***
- Develop a credentialing system for investigators and sites that is recognized and accepted by NCI, industry sponsors, clinical investigators and clinical trial sites.
***	******Investigator & Site Credentialing Repository***

## Agenda

**CTMS Team Introductions**
**What do we do?**
**How are we organized?**
**It’s been a busy year in CTMS: Progress Report and Pilot Products**

## The Structure of the caBIGTM Program

**   ****caBIGTM **

**caBIG****TM**** Architecture Workspace**

**caBIG****TM ****Vocabularies and Common Data Elements Workspace**

**Strategic Planning  Workspace**

**Training Workspace**

**Integrative Cancer Research      Workspace**

***In Vivo*****   Imaging Workspace**

**Tissue  Banks & Pathology Tools Workspace**

**Data Sharing & Intellectual Capital Workspace**

**Clinical  Trials Management Systems      Workspace**

## CTMS Organizational Structure

**  ****CTMS WS**

**CTMS Steering Committee**

**Adverse Event  Reporting**

**Study Calendar**

**Routine  Data  Exchange**

**Financial Billing**

**Structured **
**Protocol Representation**

**Laboratory        Interfaces**

**Clinical Trials Database**

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

**CRF **
**Standardization**

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

## CTMS Steering Committee Members

- Bob Annechiarico
- James Atkins
- Powel Brown
- Jan Buckner
- Chris Chute
- Walter Cronin
- Hugh Donovan
- Sharon Elcombe
- Howard Fingert
- David Gandara
- Bob Gray
- Collette Houston
- Charles Hurmiz
- Charles Jaffe
- Kim Johnson

- David Johnson
- Philip Kantoff
- Warren Kibbe
- Rebecca Kush
- Kevin Lewis
- Sorena Nadaf
- Kristin Padavic
- Electra Paskett
- Diane Paul
- Nick Petrelli
- Mitch Schnall
- Ida Sim
- Mark Watson
- Brenda Young

## Agenda

**CTMS Team Introductions**
**What do we do?**
**How are we organized?**
**It’s been a busy year in CTMS: Progress Report and Pilot Products**

## caBIGTM CTMS Critical Path circa 2006

## CTMS Pilot Products

**Biomedical Research Integrated Domain Group (BRIDG) Model**
- University of Pittsburg Medical Center, ScenPro, CDISC (Clinical Data Interchange Standards Consortium)
**caXchange**
- ScenPro
**Patient Study Calendar (PSC)**
- Northwestern University
**Cancer Clinical Central Participant Registry (C3PR)**
- Duke University
**Cancer Central Clinical Database (C3D)**
- Duke Cancer Center, Lombardi Cancer Center at Georgetown, Regents of the University of California at Irvine, Arizona University, University of Arkansas, Albert Einstein College of Medicine
**Cancer Adverse Events Reporting System (caAERS)**
- Semantic Bits
**Clinical Trials Management Systems – Interoperability**
- All

## Biomedical Research Integrated Domain Group (BRIDG) Model

**BRIDG** - **Implementation Independent Domain Analysis Model**

- caXchange
- Study Calendar
- caAERS
- C3PR
- CTMSi
- Financial SIG Model

**caAERS**

**Implementation Specific Models**

## Biomedical Research Integrated Domain Group (BRIDG) Model

**The Biomedical Research Integrated Domain Group (BRIDG) Model is a comprehensive domain analysis model representing biomedical/clinical research. It was developed to provide an overarching model that could readily be comprehended by domain experts and would provide the basis for harmonization among standards within the clinical research domain and between biomedical/clinical research and healthcare. **
**BRIDG emerged from an unprecedented collaborative effort among clinical trial experts from CDISC, the US National Institutes of Health (NIH)/National Cancer Institute (NCI), the Food and Drug Administration (FDA), Health Level Seven (HL7), and other volunteers. The modeling effort is using the HL7 Development Framework (HDF). **

## Overall goal of this project is to build a centralized message exchange hub system that can be adapted and extended to support multiple data formats. 
In release 0.5,the project integrated and leveraged core components of NCI and caBIG infrastructure.  Integrated with C3PR R1.0, leveraged caAdapter v 1.3.1 to generate HL7 v3 messages, used the CTOM database to persist the laboratory data from cancer center, implemented Security module (CSM) and the Logger Module (CLM)
Service Oriented Architecture. New services can be added to the core structure
Supports data format transformation service and converts flat file lab data into HL7 v3 messages
Supports message routing and customized workflows
Supports user authentication and authorization
Multiple deployment models – intra-institutional or inter-institutional 

**In release 0.5,the project integrated and leveraged core components of NCI and caBIG infrastructure.  Integrated with C3PR R1.0, leveraged caAdapter v 1.3.1 to generate HL7 v3 messages, used the CTOM database to persist the laboratory data from cancer center, implemented Security module (CSM) and the Logger Module (CLM)**
**Service Oriented Architecture. New services can be added to the core structure**
**Supports data format transformation service and converts flat file lab data into HL7 v3 messages**
**Supports message routing and customized workflows**
**Supports user authentication and authorization**
**Multiple deployment models – intra-institutional or inter-institutional **

- caXchange Features

## caXchange – High level data flow

- Lab data
- File in
- .csv format

**Georgetown**

- caAdapter
- (.csv to v3)

- HL7 v3
- XML

- HL7v3 CT Lab Messages with dummy clinical trial data

- C3PR Lookup

- C3PR Database

- HL7 v3
- XML

- Router

- Lab Domain APIs

- CTOM Database

- HL7v3  CT Lab Messages with actual clinical trial data

**caXchange HUB**

- C3PR Query Interface

**NCICB**

**Other Cancer Centers**

- HL7 v3

## caXchange – Detailed workflow

**Notes:**
Steps are:
 Cancer center generates a CSV file from the clinical data management system (CDMS) and puts it in a designated directory
 Hub Client picks up the raw CSV file and runs it through the preprocessor to produce a caAdapter-friendly CSV file
 Hub Client then wraps the caAdapter-friendly CSV file (the  message payload) in a SOAP wrapper and sends it to the Hub
 Hub web service receives the message and calls the authentication service
 Authentication services validates the user and passes success/failure back to web service
 Web service receives authentication success/failure and calls the authorization service
 Authorization service verifies that the user has the permission to execute the requested workflow or to route to the requested destination and passes success/failure back to web service
 Web service receives authentication success/failure and passes message to hub database
 Hub database stores original CSV message and returns message id to web service
 Web service sends an acknowledgement to hub client saying it received message
 Hub client records acknowledgement
 Web service calls workflow service and passes it the message id
 Workflow service calls caAdapter transformation service and passes it the message id
 caAdapter transformation service calls the database to query the original CSV message
 Hub database queries the original CSV message based on the id and returns the original CSV message to the caAdapter transformation service 
 caAdapter transformation service executes the transformation and calls the hub database to record the results
 Hub database stores the errors or valid HL7 v3 messages generated by the CSV transformation process and returns the id to the caAdapter transformation service
 caAdapter transformation service receives the id from the hub database and returns control to the workflow service along with the message id
 Workflow service calls the C3PR query service and passes it the message id
 C3PR query service calls the hub database to query the valid HL7 messages based on the message id
 Hub database queries the HL7 messages the returns them to the C3PR query service
 C3PR query service parses the HL7 message for the patient identifier, queries the trial/investigator info from C3PR, replaces the placeholders with real data and calls hub database to record finished message
 Hub database stores the finished (post-C3PR) HL7 message and returns id to C3PR query service
 C3PR query service receives the message id and returns control to the workflow service along with the message id
 Workflow service calls the CTOM data service client and passes it the message id
 CTOM data service client calls the hub database to query the HL7 messages based on the message id
 Hub database queries the HL7 messages the returns them to the CTOM data service client
 CTOM data service client calls the CTOM persistence web service and passes it the HL7 message
 CTOM persistence web service parses the HL7 message and executes a series of insert statements on the CTOM database
 CTOM database stores data from the insert statements
 CTOM persistence web service sends an acknowledgement to the CTOM data service client
 CTOM data service client receives the acknowledgement and audits it, returning control to the workflow service
 Workflow service identifies the end of the workflow and stops that process

## Patient Study Calendar (PSC)

**Patient Study Calendar (PSC)**

## Patient Study Calendar

**Create template of Study events and activities to quickly generate calendars for Patients.**
**View Patient schedule, reschedule or cancel Patient activities.**
**Review historical Study activities.**
**For any given time period, generate reports of activities by Site, Study, or Patient.  **

## caAERS Features

**Implemented UI for following use cases**
- Create an Adverse Event
- Collect Adverse Event Data (Lab Information)
**Integration use cases**
- C3PR – caAERS Integration
- Registration Grid Service
- caAERS – Patient Study Calendar
- Adverse Event Notification Grid Service
- Lab Viewer – caAERS
- Create Candidate Adverse Event Service
**Security**
- Login using caGrid Authentication Service
**UI look and feel**

## caAERS UI

## Cancer Central Clinical Participant Registry (C3PR)

## Cancer Central Clinical Participant Registry

**Goals of release 2**
***Integrate*** with other clinical systems
***Provide*** support for multi-site studies
***Extend*** registration, including storing randomization information
***Enhance*** protocol management, including web-based management
***Improve*** the user interface from the perspective of the registrar
***Augment*** reporting
**Progress thus far**
***Implemented*** baseline architecture
- BRIDG-compliant data model, business logic, grid services, messaging
***Developed*** flexible, pluggable web interface
- Workflows for create protocol, create subject, register subject
***Integrated*** with existing CTMS systems
- C3D, PSC, caAERS, LabViewer/CTOM
**Future plans**
- Finish up elaboration phase: complete baseline implementation
- Begin construction phase: implement rest of the use cases

## Clinical Data System (CDS)

**Protocol Abstraction – view/insert/update protocol data**
**Web – entry and submission of patient data**
**Analysis & Reporting – query and report on CDS data**

## Slide 30

## Slide 31

## C3D is a web-based clinical data management solution.
Originally developed for NCI's intramural research program
Now available to other research organizations in a hosted Application Service Provider (ASP) model
C3D supports data standardization, reuse, sharing, and interoperability through electronic Case Report Forms (eCRFs) based on Common Data Elements (CDEs) maintained in NCICB’s Cancer Data Standards Repository (caDSR) and controlled by terminology from the NCI Enterprise Vocabulary Services (EVS).
C3D supports automated submission to montitors (CTEP’s CDUS and CTMS/Theradex)

- Originally developed for NCI's intramural research program
- Now available to other research organizations in a hosted Application Service Provider (ASP) model
**C3D supports data standardization, reuse, sharing, and interoperability through electronic Case Report Forms (eCRFs) based on Common Data Elements (CDEs) maintained in NCICB’s Cancer Data Standards Repository (caDSR) and controlled by terminology from the NCI Enterprise Vocabulary Services (EVS).**
**C3D supports automated submission to montitors (CTEP’s CDUS and CTMS/Theradex)**

**Notes:**
Oracle Clinical provides support for defining the clinical trial, reusing standard templates and common data elements (CDEs), setting up electronic case report forms (eCRFs), storing data securely, and exporting data in formats compatible .
Remote Data Capture (RDC) provides a user-friendly interface that allows local and remote personnel to enter data and provides electronic confirmation of source data verification.
J-Review provides real-time reports on the clinical research data collected.

## C3D Main Interface

**Tab View**

**C3D Main Interface**

**Patient List**

**Task Tabs**

**Electronic Case Report Forms (eCRFs)**

**Activity List**

**Notes:**
Tab View: Three views are available:
Study view - Displays all CRFs in the study.
Phase view - Display of all CRFs by specific phase/interval in the study; For example, Screen, On-Therapy, Ongoing.
Visit view - Display of all CRFs by visit; For example, Screening, Course 1, Course 2, Ongoing, Off-Study.

Patient List
Displays all patients for whom some data has been entered.
Shows 8 patients at any time.
Allows you to select which 8 sequential patients to display via drop down box at top.

Task Tabs

eCRFs

## C3D PDF Data Entry

**The circle ( o ) **
**indicates that **
**you select only **
**one response.**

**The checkbox ( ******** ) indicates that **
**you may select multiple responses.**

**Italics indicate **
**that a field **
**is derived.**

## C3D Reports: J-Review

**J-Review is a Web-based tool for ad-hoc querying, reporting, and analysis of clinical data.**

**Notes:**
Note: This is fake data – not real patient data.
For example a report that shows all individuals with adverse events during the course of the study
All patients enrolled in the study who were using concomitant medications during the course of the study

## CTMS Interoperability project: BRIDG extract

## CTMS Interoperability project: sequence diagram

## CTMS Interoperability project: overview

**Goals**
- Demonstrate semantic interoperability between CTMS applications supporting *concrete *Solutions to *specific *Problems defined by a team of SMEs working in clinical trials at caBIGTM cancer centers
**Technical progress**
***Implemented ***three real-life interoperability scenarios
***Integrated***** **C3PR, C3D, PSC, LabViewer/CTOM, and caAERS
***Leveraged ***open standards
- Enterprise Service Bus (ESB), BRIDG, caGrid services, caGrid security
***Developed*** a single sign-on mechanism using caGrid security and basic web technology
**Future plans**
- Use the *structure* (integrated, multi-disciplinary project team) and *function *(iterative/incremental SEP, use of cross-application analysis model (BRIDG) of the CTMSi Project as a template for reorganizing CTMS WS

## A

***A***