# Presentation: 326884

## caTRIP Demo

*Patrick McConnell*
*Duke Comprehensive Cancer Center*
*Semantic Bits, LLC*

## Agenda

- Overview
- Problem scenario, overview, use cases
- Demo
- Core GUI, Query Builder
- Next steps
- Phase 2, beyond
- Discussion

## Who is involved

- Duke Bioinformatics
- Jamie Cuticchia (PI)
- Patrick McConnell (lead architect)
- Duke Information Systems
- Bob Annechiarico (PM)
- Wilma Stanley (developer)
- Mark Peedin (developer)
- Mohamad Farid (DBA)
- Jeff Allred (IT manager)
- Duke Pathology
- Raj Dash (domain expert)
- Chris Hubbard (developer)
- Duke Oncology
- Kelley Marcom (domain expert)
- Gretchen Kimmick (domain expert)
- Kimberly Blackwell (domain expert)
- Lee Wilke (domain expert)
- Duke CALGB
- Kimberly Johnson (DataMart liaison)

- Semantic Bits
- Ram Chilukuri (lead developer)
- Srini Akkala (developer)
- Sanjeev Agarwal (developer)
- 5 AM Solutions
- Bill Mason (developer)
- 3rd Millennium
- Julie Klemm (ICR WS lead)
- NCI
- Carl Shaefer (NCI rep)
- Subha Madhavan (caIntegrator PM)
- BAH
- Mehul Shah (tech support)

## Initial problem scenario

- Outcomes analysis: using data from existing patients to inform the treatment of another patient
- Leverage clinical, pathology, tissue, and basic science data
- Scenario:Patient A enters the clinic.  What treatments were applied with success on other patients with similar characteristics (race, sex, symptoms, pathology results, adverse events, biomarkers).

## caTRIP Beta Overview

- MAW3

- Tumor Registry

- Illumina

- caTIES

- CAE

- caTissueCORE

- TR

- CGEMSSNP

-      Duke

- Domain Grid Services

- Distributed Query Engine

- query

- discover

- GUI

- IndexService

- IdPService

- Core Grid Services

- Domain Controller

- authenticate

- caTissue CORE

- caTIES

- CAE

- TR

- caIntegrator

- GridGrouper

- authorize

## Scientific use cases

**Find available tumor tissue**
- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast and are BRCA1 positive?
**Find factors of survival**
- What are all the ER positive patients that have survived breast cancer after radiation treatment?
**Find patients for trials**
- What are all the patients that are triple negative (ER, PR, and HER2/NEU negative)?
- Determine the distribution of disease factors over time
- Determine correlation of factors pre and post surgery
- Find pathology reports of interest

**Notes:**
Find available tumor tissue
caTissue CORE: protocol #, pathological status, clinical diagnosis
CAE: ER, PR, Her-2/neu, EGFR status
Find factors of survival
Cohorts of patients who have survived a certain number of years following their diagnosis 
Tumor registry: dates of diagnosis/treatment/death, nodal/distant metastasis status, grade of tumor
CAE: ER, PR, Her-2/neu, EGFR status
SNP: BRCA1/BRCA2 status
Determine the distribution of disease factors over time
Factors that may contribute to or reflect progression of a disease state
Tumor registry: dates of diagnosis/treatment/death, nodal/distant metastasis status, grade of tumor
CAE: ER, PR, Her-2/neu, EGFR status
Find patients for trials 
Example is that of the triple negative hormone
Tumor registry: dates of diagnosis/treatment/death, nodal/distant metastasis status, grade of tumor
CAE: ER, PR, Her-2/neu, EGFR status
Determine correlation of factors pre and post surgery
Patients that have particular factors change before and after surgery 
Tumor registry: dates of surgery
CAE: ER, PR, Her-2/neu, EGFR status
Find pathology reports of interest 
Tumor registry: dates of diagnosis/treatment/death, nodal/distant metastasis status, grade of tumor
CAE: ER, PR, Her-2/neu, EGFR status
caTIES: pathology report
Find SNP results correlated with factors
Tumor registry: nodal/distant metastasis status, grade of tumor
CAE: ER, PR, Her-2/neu, EGFR status
SNP: BRCA1/2 status, genotype finding, gene biomarker

## caTRIP Demo

*Patrick McConnell*
*Duke Comprehensive Cancer Center*

## Phase 1 scientific queries Find available tumor tissue

- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast and are BRCA1 positive?

## Phase 1 scientific queries Find factors of survival

- What are all the ER positive patients that have survived breast cancer after radiation treatment?

## Phase 1 scientific queries Find patients for trials

- What are all the patients that are triple negative (ER, PR, and HER2/NEU negative)?

## Dynamic Service Discovery

## Phase 1 scientific queries Find available tumor tissue

**Phase 1 scientific queries** Find available tumor tissue

- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast and are BRCA1 positive?

**caTissue CORE**

**CAE**

**Tumor Registry**

**CGEMS**

**Participant ****Medical Record Number**

## Phase 1 scientific queries Find available tumor tissue

- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast and are BRCA1 positive?

- <DCQLQuery xmlns="http://caGrid.caBIG/1.0/gov.nih.nci.cagrid.dcql">
-     <TargetObject name="edu.wustl.catissuecore.domainobject.impl.TissueSpecimenImpl" serviceURL="http://152.16.96.114/wsrf/services/cagrid/CaTissueCore">
-         <Association name="edu.wustl.catissuecore.domainobject.impl.SpecimenCollectionGroupImpl" roleName="specimenCollectionGroup">
-             <Association name="edu.wustl.catissuecore.domainobject.impl.ClinicalReportImpl" roleName="clinicalReport">
-                 <Association name="edu.wustl.catissuecore.domainobject.impl.ParticipantMedicalIdentifierImpl" roleName="participantMedicalIdentifier">
-                     <Group logicRelation="AND">
-                         <ForeignAssociation>
-                             <JoinCondition>
-                                 <LeftJoin>
-                                     <Object>edu.wustl.catissuecore.domainobject.impl.ParticipantMedicalIdentifierImpl</Object>
-                                     <Property>medicalRecordNumber</Property>
-                                 </LeftJoin>
-                                 <RightJoin>
-                                     <Object>edu.duke.catrip.cae.domain.general.ParticipantMedicalIdentifier</Object>
-                                     <Property>medicalRecordNumber</Property>
-                                 </RightJoin>
-                             </JoinCondition>
-                             <ForeignObject name="edu.duke.catrip.cae.domain.general.ParticipantMedicalIdentifier" serviceURL="http://152.16.96.114/wsrf/services/cagrid/CAE">
-                                 <Association name="edu.duke.catrip.cae.domain.general.Participant" roleName="participant">
-                                     <Association name="edu.pitt.cabig.cae.domain.general.AnnotationEventParameters" roleName="annotationEventParametersCollection">
-                                         <Association name="edu.pitt.cabig.cae.domain.breast.BreastCancerBiomarkers" roleName="annotationSetCollection">
-                                             <Attribute name="HER2Status" predicate="LIKE" value="POSITIVE%"/>
-                                         </Association>
-                                     </Association>
-                                 </Association>
-                             </ForeignObject>
-                         </ForeignAssociation>
-                         <ForeignAssociation>
-                             <JoinCondition>
-                                 <LeftJoin>
-                                     <Object>edu.wustl.catissuecore.domainobject.impl.ParticipantMedicalIdentifierImpl</Object>
-                                     <Property>medicalRecordNumber</Property>
-                                 </LeftJoin>
-                                 <RightJoin>
-                                     <Object>edu.duke.cabig.tumorregistry.domain.PatientIdentifier</Object>
-                                     <Property>medicalRecordNumber</Property>
-                                 </RightJoin>
-                             </JoinCondition>
-                             <ForeignObject name="edu.duke.cabig.tumorregistry.domain.PatientIdentifier" serviceURL="http://152.16.96.114/wsrf/services/cagrid/CaTRIPTumorRegistry">
-                                 <Association name="edu.duke.cabig.tumorregistry.domain.Patient" roleName="patient">
-                                     <Association name="edu.duke.cabig.tumorregistry.domain.Diagnosis" roleName="diagnosisCollection">
-                                         <Attribute name="primarySite" predicate="LIKE" value="BREAST%"/>
-                                     </Association>
-                                 </Association>
-                             </ForeignObject>
-                         </ForeignAssociation>
-                         <ForeignAssociation>
-                             <JoinCondition>
-                                 <LeftJoin>
-                                     <Object>edu.wustl.catissuecore.domainobject.impl.ParticipantMedicalIdentifierImpl</Object>
-                                     <Property>medicalRecordNumber</Property>
-                                 </LeftJoin>
-                                 <RightJoin>
-                                     <Object>gov.nih.nci.caintegrator.domain.study.bean.StudyParticipant</Object>
-                                     <Property>studySubjectIdentifier</Property>
-                                 </RightJoin>
-                             </JoinCondition>
-                             <ForeignObject name="gov.nih.nci.caintegrator.domain.study.bean.StudyParticipant" serviceURL="http://152.16.96.114/wsrf/services/cagrid/CGEMS">
-                                 <Association name="gov.nih.nci.caintegrator.domain.analysis.snp.bean.SNPAnalysisGroup" roleName="analysisGroupCollection">
-                                     <Attribute name="name" predicate="LIKE" value="BRCA1%"/>
-                                 </Association>
-                             </ForeignObject>
-                         </ForeignAssociation>
-                     </Group>
-                 </Association>
-             </Association>
-         </Association>
-     </TargetObject>
- </DCQLQuery>

**HER2/NEU Positive**

**Foreign Join w/ CAE **

**Foreign Join w/ Tumor Registry **

**Primary Site Breast**

**Foreign Join w/ CGEMS **

**BRCA1 Positive**

**Select tissue**

## caTRIP Next Steps

## caTRIP next steps

- Add functionality
- GUI, DQE
- Implement security
- Authorization, authentication
- Add audit capabilities
- Common logging component
- Implement compliance
- Section 508 and 21 CFR part 11
- Add datasets
- CAE, SNP

## Beyond phase 2

- Invocation of analytical services
- Building workflows
- Adding data visualization
- Asynchronous querying

## Discussion

## Backup slides

## Tumor Registry

- Created from Duke TR database
- Submitted model for loading into the DSR
- Duke
- Validated model
- Provided real de-identified test data
- Data Loading
- Delimited data files
- Hibernate API
- Available at GForge under caTRIP project

## Tumor Registry Model

**Participant**

**Diagnosis**

**Treatment**

**Follow up and ****Recurrence**

**Collaborative ****Staging**

## Loading test data

- Identified sample data
- Queried various Duke databases
- Googled cancer websites
- Built input files
- Text files with values that correspond to CDEs
- Loaded data
- Randomly selected values from text files
- Used Hibernate APIs to load objects

## Data loading example

- CuratedData Files

- DB

- Data Generator

- Participant

- load viahibernate

- randomlyselect

- generateobjects

| Liles                      | MARY |
| --- | --- |
| Harris                     | PATRICIA |
| Kennedy                    | LINDA |
| Wynne                      | BARBARA |
| Lytle                      | ELIZABETH |
| Lytle                      | JENNIFER |
| Tamborella                 | MARIA |
| Chopra                     | SUSAN |
| Denny                      | MARGARET |
| . . .                     | . . . |

- Maria

- Kennedy

- Participant

- Linda

- Liles

- Participant

- Susan

- Wynne

- Participant

- Barbara

- Chopra

**. . .**

## caTRIP data system statistics

## Data sharing challenges

- Sharing identifiable data
- Step 1: caTRIP gets IRB approval to build a system
- Step 2a: researcher gets IRB approval for protocol to view data
- Step 2b: clinician uses data for *patient care *(trickier than it sounds) or *quality of service*
- Sharing deidentified data
- Traditional method: data manager deidentifies an entire dataset then throws away the key
- Centralized: not scalable
- Proposed method: trusted service provider (TSP) deidentifies discreet values
- Distributed: everyone is responsible for their own deid
- Very scalable

## Distributed deidentification

- Trusted Service Provider

| PHI                     | DEID |
| --- | --- |
| MRN1                     | ABC123 |
| MRN2 | DEF456 |
|  |  |
| . . .                     | . . . |

- MRN3

- GHI789

- MRN3

- GHI789

- Randomly generated

- Has IRB approval to see identifiable data

- Has IRB approval to see identifiable data

- Has IRB approval to store identifiable data

- Secure connection

| PHI                     | DEID |
| --- | --- |
| MRN1                     | ABC123 |
| MRN2 | DEF456 |
| MRN3  | GHI789 |
| . . .                     | . . . |

## caTRIP data sharing

- Current deidentified datasets (via modified centralized way)
- caTissue CORE, Tumor Registry
- Future deidentified datasets
- CAE, SNP
- Goals
- Get IRB approval at Duke for sharing identifiable data
- Modify Duke deidentification policy to allow distributed model
- Use caTRIP as one model for data sharing in caBIG

## Phase 1 scientific queries Find available tumor tissue

- What are all the available tissue specimens from the breast?
- What are all the tissue specimens from patients that have a her2/new status of positive?
- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast?
- What are all the tissue specimens from her2/neu positive patients that have a primary tumor in the breast and are BRCA1 positive?

## Phase 1 scientific queries Find factors of survival

- What are all the ER positive patients that have survived breast cancer after radiation treatment?
- What are all the BRCA1 positive patients over the age of 50 that have survived breast cancer after surgery?

## Phase 1 scientific queries Find patients for trials

- What are all the patients that are triple negative (ER, PR, and HER2/NEU negative)?

## caTRIP Next Steps

*Patrick McConnell*
*Duke Comprehensive Cancer Center*

## caTRIP next steps

- Add functionality
- GUI, DQE
- Implement security
- Authorization, authentication
- Add audit capabilities
- Common logging component
- Implement compliance
- Section 508 and 21 CFR part 11
- Add datasets
- CAE, SNP

## GUI enhancements

- Reporting
- Data-mining style reporting
- Filters
- Drop-down values for enumerated value domains and distinct values
- Filter type based on data type
- Groups of ORs and ANDs
- Query sharing and synchronization
- Synchronize DQCL, simple, and advanced GUI
- Share new queries, invoke existing queries

## DQE enhancements 

- Service
- Grid service for DQE
- Delegation
- XML-based processing
- Generalize to any grid service
- DCQL enhancements
- Define return type (associated objects)
- Return distinct values or single attributes
- Implementation
- Distributed joins other than equality

## Security

- caGrid Authentication Service

- SAML Assertion

- User Credentials

- Dorian

- Duke Authentication Plugin

- Duke Domain ControllerNT Security

- Grid Data Service

- User Grid Certificate

- CSM

- backenddata

- authentication

- authorization

- GridGrouper

- Trust Fabric

## Auditing module

- Hibernate

- Domain DB

- CQLProcessor

- Grid Service

- SecurityCall-out

- CSM

- caLog

- user

- D/CQL

- HQL

- results

- Log DB

- GUI

- Log File

- or

- caLog?

- CLM?

- caGrid Authentication Service

- caLog?

**. . .**

## Compliance

- Section 508
- Mostly pertain to usability for people with vision impairments.
- Examples
- Alternative keyboard navigation
- Animated displays, color and contrast settings, flash rate, and electronic forms
*Implemented by simplified GUI input form*
- 21 CFR part 11
- Ensures the authenticity, integrity, non-repudiation and confidentiality of electronic records and signatures
*Implemented by the logging module*

## Beyond phase 2

- Invocation of analytical services
- Building workflows
- Adding data visualization
- Asynchronous querying