# Presentation: 943874

## The caBIG/HL7/CDISC Structured Protocol Representation

- Douglas B. Fridsma, MD, PhD
- Center for Biomedical Informatics
- Center for Pathology and Oncology Informatics
- University of Pittsburgh

***John Speakman***

## Agenda for today

- A short history of the model and what it does
- (aka caSPR, aka Problem Space Model, aka DAM, aka DSAM)
- CaPRI and the Development Framework
- How this workspace could/should get involved

## A Team Effort

**Core modeling team:**
- Christo Andonyadis** (NCICB)**
- Greg Anglin** (Eli Lilly)**
- Lisa Chatterjee** (Digital Infuzion / NIAID)**
- Julie Evans** (CDISC)**
- Doug Fridsma** (UPCI)**
- Smita Hastak** (ScenPro / NCICB)**
- Ray Heimbuch** (Novartis)**
- Charlie Mead** (Oracle / HL7)**
- Joyce Niland** (City of Hope)**
- John Speakman** (Memorial Sloan-Kettering)**
- Cara Willoughby** (Eli Lilly)**
- Diane Wold** (Glaxo SmithKline)**

**Leadership: **Sue Dubman (NCI), Becky Kush (CDISC), Charlie Mead **(HL7 RCRIM / Oracle)**, Linda Quade **(HL7 RCRIM / Eli Lilly)**, Barbara Tardiff **(HL7 RCRIM / Merck)**, Randy Levin **(HL7 RCRIM / FDA)**

## Clinical Data Interchange Consortium (www.cdisc.org)

-  Site CRFs
- Laboratories
- Contract
- Research
- Organizations
- Development
- Partners

_*Operational*_
_*Database*_
- Study Data
- Audit Trail
- Metadata

- Operational
- Data
- Interchange
- & Archive:
- ODM, LAB

_*Submission *_
_*Data*_
- CRT/Domain   Datasets
- Analysis   Datasets
- Metadata

- Submission
- Data
-  Interchange
-  & Archive:
- SDM, ADaM

**Clinical Data Interchange Consortium (www.cdisc.org)**

- ODM = Operational Data Model  	 SDM = Submission Data Model
- LAB =  Laboratory Data Model    	 ADaM = Analysis Data Models

- One harmonized CDISC standard/model

-  Protocols
-  SEND

## ODM

**Operational Data Model**
** **XML format for clinical study
- data and metadata
- Supports regulatory-compliant
-  e-Archive format

- SDS
**Submission Data Standards**
- *Describes content, structure and attributes of
- data for regulatory submissions
- *Defines metadata content for standard domains
- *Facilitates regulatory reviews

- LAB
**Laboratory **
**Data Model**
-  Defines standard content for
- transferring clinical laboratory
-  data  from labs to sponsors
- ASCII, SAS, XML, and
- HL7 implementations available

-          ADaM
**             ****Analysis **
**        ****Dataset Models**
- Provides models for commonly used statistical analyses.

- Operational Data Modeling

- Submission Data Modeling

*Data*
*Sources*

*Regulatory*
*Reviewers*

***LAB data ***
***can be mapped ***
***into ODM XML***

***Applies submission ***
***model for ***
***analysis datasets***

*ODM can be used to represent *
*and archive submission data*

*ODM values can be expressed via SDS metadata *
*	*

*define.xml*

## The world’s leading standard for the electronic interchange of healthcare information 
>20 Global affiliates
16 years of operation
ANSI-accredited SDO, acknowledged by the DHHS as the standard for healthcare information exchange
RIM (Reference Information Model)
RCRIM (Regulated Clinical Research Information Management) Technical Committee

- >20 Global affiliates
- 16 years of operation
- ANSI-accredited SDO, acknowledged by the DHHS as the standard for healthcare information exchange
- RIM (Reference Information Model)
- RCRIM (Regulated Clinical Research Information Management) Technical Committee

**Health Level Seven (www.hl7.org) **

**Notes:**
By this point in the Conference, we’ve all had plenty of introductions to HL7, so I won’t read this slide

## Slide 7

## CDISC and HL7 Relationship

- 2001-2002:
- Early CDISC attempts to map CDISC ODM (Operational Data Model) to the HL7 RIM failed
- 2003:
- CDISC-HL7 joint study group to assess how CDISC standards might become RIM compliant and be grafted onto HL7 RIM
- Plan developed for creating domain-space ‘business’ model for clinical research
- 2004: Modeling starts

## Domain Space Analysis Model: Timeline

**Domain Space Analysis Model: Timeline**

- Early attempts to map ODM to HL7 RIM

- Dr. Mead’s Report to CDISC Board of Directors

- Initial DSAM Development, led by Dr.Mead

- Feedback Review of DSAM with Focus Groups

- Begin Mapping CDISC ODM to HL7 V3 RIM

**2001-2002**

**Jan 2004**

**Mar-Aug 2004**

**Aug-Oct 2004**

**Dec 2004**

- ...

- Reps from:
- NIH/NCI
- FDA
- EHR/eSource
- TCC
- HL7 RCRIM
- CDISC teams
- CDISC IAB

- Reps from:
- CDISC Board
- CDISC Teams
- HL7 RCRIM
- TCC
- NCI

- Involvement from:
- CDISC
- NCI
- RCRIM inv.

**2003**

- HL7 V3 RIM Implementation of
- CDISC LAB Model ->
- ANSI Accreditation;
- Assistance for ODM sought
- from L.Bain, C.Mead

- Initial Modeling of Protocol Elements in DSAM

- Reps from:
- CDISC
- NCI/caBIG
- HL7 RCRIM

**Nov 2004**

- Reps from:
- CDISC
- HL7

- ODM Production V1.2 (XML Schema)  - Industry Adoption and Tool Development  

- SDTM Announced by HHS/FDA;
- eSubmission made w/ define.xml

## Interchange Standards:  Long-term Desired Outcomes

- A holistic approach to standards, facilitating data interchange from sites through regulatory submission, utilizing XML
- Standards for data acquisition supporting the population of a cross-trial warehouse within FDA
- HL7-CDISC models harmonized to yield value for both clinical research and healthcare – sharing of information between EMR and clinical trials
- Global adoption of CDISC data standards

***CDISC Meeting with FDA Commissioner, April 2003***

## CDISC Plans

- Today, CDISC is working to ensure interoperability among its own standards.
- CDISC has committed to using the HL7 Development Framework (HDF) as a process through which the CDISC standards are to be harmonized with the HL7 RIM in the long term.
- The ultimate goal is one overarching model to support interoperability between healthcare and clinical research systems.

## The “World of Clinical Trial Standards” 

**Protocol Std**

**The “World of Clinical Trial Standards”**

**= ****Organization**

**= Dictionary,**
**    ****Codelist****	****	**

**= ****Standard**

**= ****Model**

**= Document Standard,**
**   ****or Architecture**

**TC:**
**RCRIM**

***Source: Becky Kush, mod.Cara Willoughby***

## Vision of the SPR SIG (July 2004)

- To:
*Define* a computable protocol representation that supports the entire life-cycle of a clinical trial protocol
*Develop* *tools* that use this protocol representation.
- The protocol representation will serve as a *foundation* for caBIG modules that support *all phases* of the clinical trials life cycle (including protocol authoring)

## Today’s Clinical Trial Protocol

- One full-text source presented several ways

***Source: Greg Anglin, Eli Lilly***

**Notes:**

That document can be rendered into many other formats, but there is still one full-text source.

TRANSITION:
This is today’s convention for the protocol, and for the most part, any other clinical document within clinical research.
I’m here to introduce you to tomorrow’s vision for the clinical trial protocol.

## Tomorrow’s Clinical Trial Protocol

- A data layer in the full-text source

- Data layer

**Tomorrow’s Clinical Trial Protocol**

**Notes:**
...documents can be married with technology because a data layer is introduced within the full-text source.

This data layer can then be used to feed downstream activities within the trial.

TRANSITION:
This has been the vision for the future of protocols and has been the objective of a standards developing group called...

## Interchange vs. Interoperability

**interoperability** **:** ability of two or more systems or components toexchange information and to *predictably* use the information that has been exchanged.	Source: IEEE Standard Computer Dictionary: A Compilation of 		IEEE Standard Computer Glossaries, IEEE, 1990]

**Syntax ******** Structure**
**Semantics ******** Meaning**

***Source: Charlie Mead, HL7***

## The Semiotic Triangle:How Humans Communicate

***Source: Charlie Mead, HL7***

## “Protocol” and the Semiotic Triangle

***Symbol***
***“******Protocol******”***

## Some HL7 Terms 

- Mood:
- Lifecycle of a concept through a business process
- State:
- Lifecycle of an instance

**Notes:**
HL7 offers some new and not so new terms that help us to resolve this semantic quandry

- Propose

- Plan

- Execute

- Report

**Study**

- Concept

- Business
- Process

**Protocol**

- Document

- Instance

## Study

- Document

- Intent

- Plan

- Execute

- Report

**Study**

**MOOD:**Lifecycle of a research concept through a business process

**STATE: **Lifecycle of an instance

**Protocol:****A document that contains study information in the planning mood.**

## Basis of the Model

- CDISC Protocol Elements Spreadsheet
- Contains definitions of ~200 concepts deemed important to clinical research
- But no structure (i.e., no representation of their relationships)
- Job #1: build a model that includes all the concepts in the speadsheet

## The iterative process of creating the SPR: Stage I

- HL7v3 RIM

- Domain elements
- (drawn from CDISC
- PR elements)

- * at this stage there are granular ideas that we know we need to represent, but relationships not clear

- Business Inputs

## CDISC protocol elements

## The iterative process of creating the SPR: Stage II

- HL7v3 RIM

- Strawman model of structure of domain elements

- * at this stage we describe the relationships between domain elements, without regard for the RIM

- Business Inputs

## Slide 26

## Slide 27

## The iterative process of creating the SPR: Stage III [now]

- Business Inputs

- reductionist model of structure of domain elements

- * at this stage we analyze the model to boil it down to its primitive data structure.  It gets close to RIM, but very abstract ... loses some meaning to domain experts

- HL7v3 RIM

## The Model: Stage II-III

## The iterative process of creating the SPRStage Two       Stage Three       Stage Four

*The iterative process of creating the SPR*Stage Two       Stage Three       Stage Four

## The iterative process of creating the SPR: Stage IV

- Business Inputs

- RIM

- integrated model(s) of structure of domain elements

- Explode back to domain concepts, through instance diagrams, storyboards,vocabularies, and other tools; check that the initial elements still hold in the model

## ECOG 2190 Schema

## ECOG 2190 Protocol Activity

## caSPR forms the foundation for interoperable module development

## Proposed caPRI System Description

## Portions currently implemented

- EAV database

## Slide 37

**Notes:**
This is essentially an About box

## Slide 38

**Notes:**
Form Management screen for making extensions and creating new forms

## The Importance of Process

- We need processes to develop interoperable applications
- Can use the HL7 Development framework
- We need processes to develop interchange standards
- Again can use the HL7 Development Framework
- We need processes to maintain the Model
- Collaboration
- Versioning control
- Model harmonization

## A example development process—caPRI

- caDSR candidate CDEs

- caSPR module analysis model

- caSPR CDE

- caPRI input module (module specification)

- caPRI CT management framework

- RCRIM DMIM

- RMIM (interchange requirements)

- HL7 XSD (Interchange specification)

- HL7 compliant framework

- caSPR =
- CDISC DSAM =
- HL7 DAM

- Semantic connector & UML loader

- Increasing specificity and computability

- Functional Requirements

- Application Development

- Interchange Specification

## The people processes – Desiderata for a collaboration web-board-type thing

- Open access, open communication, discussion forums
- Mechanisms for proposing changes
- Mechanisms for harmonization
- Levels of access (readers, modelers, stewards)
- Tightly controlled versioning with tracking
- Integration of model packages, application code, documentation, and user groups

## What have we accomplished?

**caSPR**
- Established excellent collaboration with CDISC, HL7 and other caBIG modelers
- Constructed the initial pieces of a comprehensive model
- still much to do
- Established this model as the HL7 Domain analysis model
- Have established Enterprise Architect as the tool of choice, and moved the model from Rational Rose XDE into EA

## What have we accomplished?

**caPRI**
- Demonstrated a caBIG compliant application that is modular, extensible, flexible, and driven from the SPR model
- Set the stage for collaborative development of new modules and features
**Process**
- Proposed a model development, collaboration, and version control process

## The caFuture

## What we need

**Ask not what the structured protocol representation can do for you, **
**Ask what you can do for the structured protocol representation**

## Current caBIG/HL7/CDISC SPR needs

- Developing Instance diagrams, examples, and testing the model using the ECOG 2190 protocol as our initial test
- The model is “static” heavy
- Develop the behavioral portions of the model
- The people processes around clinical trials
- Calendars
- Activities
- Behaviors
- Study execution

## Next steps in the SPR project – our tasks

- caSPR
- Dissemination and presentation—road shows
- caBIG April 10th, HL7 May 2nd, CDISC middle/end of May
- Development and implementation of model versioning control and collaboration processes
- People and technical processes to be finalized
- Incorporation of informal comments and correction of known model problems
- Next core modeling session next week!

## Next steps in the SPR project

- Model development needs
- Review class and attribute definitions
- Assistance with instance diagrams and examples
- Requirements gathering for new functionality and subdomains
- Application development needs
- Adopters of caPRI – testing and improvement
- Developers of new modules

## Next steps in the SPR project

- Integration within CTMS and across caBIG
- SIGs should be the leads in the requirements and testing of the parts of the model that they have expertise in
- Other workspaces activities will touch on the SPR
- Tissue banking and pathology tools
- i.e., us

## TBPT involvement

- Include a stub to the caTISSUE OM?
- How big is the stub?
- Or just include the whole caTISSUE OM within it?
- When is a tissue protocol something we “care” about?
- When is it just another “protocol” like the IRB protocols we know and love?
- What does it depend on?
- Consent type?
- IRB involvement?
- Assignment of an IRB number?
- Annotation of specimens?
- *shrug*