©

OpenClinica in an Integrated

Translational Environment

Using OpenClinica to the max

Marinel Cavelaars & Jacob Rousseau

CTMM-TraIT / VU University Medical Center

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Presentation outline

Overview TraIT

Overview TraIT OpenClinica deployment:

OpenClinica environments

Performance concerns

Integration issues

Integration: Trusted Third Party, Single sign-on

Interoperability: link to images, data upload, link with EHR,

link with DWH

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CTMM TraIT project aim

Sustainable research IT infrastructure for biomedical research

projects:

Facilitate the collection, storage, analysis, archiving and securing

of the data generated in Dutch medical research projects

Accelerate translational research; facilitate multi-center

collaboration and data sharing within translational research

projects

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TraIT amendment 3, 2014: 30 partners

Growing TraIT project team

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Scope of TraITTraIT typically supports

Translational biomedical research, i.e. customer projects normally

include a clinical data component

Projects that are either multi-center or multi-domain (clinical, imaging,

biobanking, experimental)

Investigator-driven studies or clinical registries

Late-stage product trials leading directly to an FDA/EMEA registration

dossier are not within the regular scope of TraIT

Patient safety shall not directly depend on the information in TraIT

systems

Projects initiated from The Netherlands (including foreign partners)

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Division in work packages

Five data generating

work packages

Data integration & analysis

across the four platforms

Shared service center for

hardware, training & support

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High-level TraIT data flows

Translational Research (IT)

Samples (IT)

Hospital (IT)data

domainsclinical

imaging

experimen

t

biobanking

integrated

data

translational

research

workspace

Public Data

TranSMART

CBM

BMIA

XNAT

e.g. R

T

T

P

Open

Clinica

Various

solutions

HIS

PACS

LIS

BIMS

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Uptake of TraIT OpenClinica

0

10

20

30

40

50

60

70

80

90

100

July 2008 Oct

2011

Oct

2012Start DeCoDe

OpenClinica Start TraIT

OpenClinica

Oct

2013 June

2014

num

ber

of stu

die

s

Pre TraIT effect:multicenterVUmc studies

Also multicenterstudies other Dutch UMC’s

91 studies

131 sites496 users

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TraIT OpenClinica services

Hosting OpenClinica environments via professional provider

Application and Change Management by TraIT technical support staff

OpenClinica user supportVia TraIT servicedesk (Topdesk / Email / Tel)User TrainingUser Manuals and Documentation

Costs of hosting and (user) support are currently covered by the CTMM-TraIT project. A business model is being developed for the period after January 2016.

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OpenClinica-related deliverables for 2014

Twenty-three standard CRFs including concept mapping

OpenClinica Data Importer improvements (e.g. integration with Web Services)

Link to EHR’s for automated data upload into OpenClinica

New/improved OpenClinica features

Dynamic links in CRF (e.g. link to image): OC version 3.3!

Web services improvement for (fully automated) data upload

Authorization more granular: on Event or CRF level

Link/data pipeline between OpenClinica and TranSMART DWH

Integration OpenClinica with external subject id provider (Trusted Third Party;

TTP)

Interoperability between scheduling tool (Logis) and OpenClinica

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CTMM TraIT – Applications

Clinical data

OpenClinica

TraIT-wide

Trusted Third

Party

Imaging

BMIA & XNAT (Pacs)

Data integration

TranSMART

Experimental Data

Phenotype-DB

Pathology Imaging

tEPIS

Biobanking

Biospecimen catalogus /

workflow sample request

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OpenClinica.nl

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OpenClinica environments

Production 1 – single instance / multiple active studies

Production 2 – single instance / one large non-active

study

Sandbox – for study and CRF development

Acceptance – for technical tests and problem solution

Test / Development – for feature testing and

development

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Typical setup VM’s

VM1

Apache 2.2

Web-server

VM2

Tomcat 6.0.32

MirthConnect 2.20

VM3

Postgres

8.4.12

Internet

AJP 1.3 JDBC

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Statistics

Approximately 220 users per month (50 per workday)

Mostly Dutch users

91 studies / 496 users

Small investigator initiated studies (n subjects < 100)

Small / medium registration studies (n subjects < 5000)

Large registration study (n subjects = 177509)

Total subjects in the production environment: 19265

AWstats ( http://awstats.sourceforge.net/ )

Overview of users and visit details

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Performance issues

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Performance issues

Factors likely to play a role but not investigated in detail yet:

Suboptimal OpenClinica source code from a performance point

of view

Complex database queries and sub-optimal joins

Load on OpenClinica. Several factors may play a role:

Number of data objects in the database (increases with

increasing number of studies)

Number of concurrent users

Complexity of CRFs (Java-scripting, rules, large amount of items per

CRF)

It is always difficult to pin-point the causes of performance problems;

other factors may be relevant as well.

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Performance factors

Factors currently identified to play a role in the performance:

Indexing of tables in the database: adding an index in Jan 2014

solved export performance issue

Local factors (on client side): browser type and version,

institute’s firewall, operating system (windows version),

computer disc space, memory and CPU

Virtual Machine configuration

Web-front end configuration (Images / CSS / Javascript cache)

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Performance measurements

Performed from a single client behind a typical hospital

firewall

One to eight concurrent users running the same

Selenium script

Create subjects and add data in a simple study

Create subjects and add data in a complex study

Navigate through the study (Subject matrix, audit log etc)

Run as JUnit tests concurrently with a special runner

and headless FireFox with X virtual frame buffer (Xvfb)

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Measurements points

Tomcat log with a valve

Postgres log (configuration option to log all queries and

their duration)

Browser plugins (WebDeveloper and Firebug)

VM-ware

JUnit script duration (client-side)

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Stress measurements -Tomcat - total duration of scripts per number of concurrent users

0

100000

200000

300000

400000

500000

600000

1 2 3 4 5 6 7

total duration [ms]

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Stress measurements -clientside

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Scaling / optimization ideas Multiple OpenClinica instances with load balancing on

the web-server

VM improvements

Upgrade of Postgres

Hardware

Multi-threaded

Database optimization ( indexes )

Code improvement ( Hibernate )

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ICT TraIT – Clinical data acquisition

work-package

OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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Trusted Third Party Integration

To enable secure matching of Personal Identifying

Information such as Social Security Number or Hospital

ID’s with OpenClinica studySubjectID’s

In cooperation with CTMM-TraIT partner Custodix.be

Legislation (Dutch) disallows the transport of

unencrypted SSN. HIS ID’s however are allowed over

SSL.

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TTP technical implementation

Subject registration with Hospital Information System number /

Social Security Number

OpenClinicaTrusted

Third

Party

Client

Browser

Internet

Web-service

adapter

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New study parameter option

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OCDataImporter

OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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OCDataImporter

Developed since 2012 by Cuneyt Parlayan (CTMM-

DeCoDe project; VU University Medical Center)

Tool to convert tab-delimited files to ODM

Design considerations

Consistency and data-format checks to enable automated uploads

Clear error reporting

To be used by data managers

Automated column name to items matching

To be downloaded from

OpenClinica WIKI wiki.openclinica.com

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OCDataImporter

Windows UI-application

Loading of the study meta-data file and a CSV-file

Automatically map of columns to OpenClinica data items

Integration of WS-calls for subject creation and event creation &

scheduling. OpenClinica code must be adapted to allow (OC version

3.4?):

Single WS-operation to create subject, create and schedule

event

Configurable event status after upload

Query event status for single subject

Automated operational mode for automated ETL

OCWS tool for use with MirthConnect

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OCDataImporter

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Integration with EHR-system

OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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EHR integration

Use MirthConnect input channels

HL7 v2 or v3

Export from a hospital system e.g. CSV

IHE Retrieve Form for Data capture (RFD)

Use the TraIT applications OCWS or OCDataImporter to

convert the messages to ODM

Import into OpenClinica either by Web-services or by a

scheduled import job

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Integration with imaging systems

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OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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Integration image archives

www.bmia.nl (BioMedical Image Archive) is a CTMM-

TraIT PACS

Specific use case: store radiologist assessments of images

in an OpenClinica CRF

Development with OpenClinica LLC of a ‘parameterized

link’ where item values and study fields can be substituted

and displayed in the CRF

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Parameterized link

<a href="http://www.acc.bmia.nl/restViewer.php?

pid=${studySubject}

&study=${item['SCAN_TYPE']}

&series=${item['DICOM_SERIES']}|Corrected

&debug=1

&subject=${studySubject}

&studyName=${studyName}

&event=${eventName}”

target="_blank">Review Image</a>

Entered in the left / right item text fields in the CRF in OpenClinica

version 3.3:

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Demo parameterized link

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Demo parameterized link

_http://www.acc.bmia.nl/restViewer.php?pid=P0039C0006I1319777

&study=PETCT&series=CT12062012105757|Corrected

&debug=1&subject=P0039C0006I1319777&studyName=TestParameterizedLinks

&event=Radiologist_Review&ordinal=1&crfName=TPL_CRF&crfVer=0.19

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Single sign-on

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OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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Single Sign-On

Currently investigating the possibilities for a single sign-

on for all TraIT applications

Using the Dutch national university network Surfnet and the

SAML 2.0 federated sign-on ( SurfConext )

Single user registry which is maintained by the participating

universities and institutions

Possibly develop a portal solution for single sign-on to all

CTMM-TraIT applications

Add a custom implementation of the existing (Spring-

based) authentication manager

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Export / storage on Data Warehouse System

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OpenClinica

Trusted

Third Party

BMIA

(Pacs)

tranSMART

Logis

EHR-systems

SurfConext

MirthConnect

OCDataImporterI2B2

tEPIS Pathology

imaging

Open Clinica Web services

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Transferring clinical study data from OpenClinica to

tranSMART enables:

the analysis of the study data (e.g. statistics)

the integration with other data (e.g. genomics)

cross-study analysis

tranSMART uses the database format i2b2 in which data is imported via tabular text files

Ideally, we create an automated conversion from ODM to i2b2

Purpose

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Data flow and tools

ODM

file(s)

OpenClinica

ODM export

OC-

concepts

based

tabular

data

TM-

concepts

based

tabular

data

ODM2Tabular

translator

concept

translator and

filter

OC tranSMART

OC-TM

concept

mapping

tranSMART

clinical data

upload

tranSMART

clinical data

upload

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Model interventional study

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Model observational study

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Acknowledgements

The OC14 organizers, e.g. Ben Baumann, Cal Collins, Rob Ritberg

OpenClinica developers and testers, Alicia Goodwin, Chris Connor,

Douglas Rodrigues, Krikor Krumlian, Hiroaki Honshuku, Steve

DiBona, Jamuna Nyayapathi, and others ...

TraIT participants, Trial Data Solutions (Gerben Rienk Visser &

Annelies Rotte), Cuneyt Parlayan, Jacob Rousseau, Marinel

Cavelaars, Henk Verheul, Jeroen Beliën, Annemarie Verburg, Rita

Azevedo, Ruud Ross, Sander de Ridder, Jan-Willen Boiten, Johan

van Soest, Ward Blondé, Arjan van der Velde, and many more….

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Content of tabular data

subj01 43 Yes 408 Deceased ..

subj02 67 No Living ..

subj03 29 No 173 Deceased ..

.. .. .. .. .. ..

1 SUBJ_ID

2 Subjects+Age

4 EndPoints+days to death

5 Endpoints+vital status

.. ..

observations file

column–concept mapping file

A column contains the observations of a specific concept

One of the columns contains the subject-id's

A row contains the observations of a single subject

A separate file contains the mapping between columns, concept paths (a path in the ontology tree in tranSMART's data explorer UI), and ontology terms (not yet in OC)

Unmapped columns are not uploaded

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OC based tabular data

Observation file can be build from ODM file.

Concept paths in mapping file can only be based on Open

Clinica concepts (Event, Form, …) which also can be

found in the ODM file.

Uploading these files directly in tranSMART would result in an

Open Clinica style ontology tree

1 SUBJ_ID

2 Patient Information+Age

3 Patient Information+Married

4 Closing Event+survival time

5 Closing Event+survival status

.. ..

subj01 43 Yes 408 Deceased ..

subj02 67 No Living ..

subj03 29 No 173 Deceased ..

.. .. .. .. .. ..

observations file

column–concept mapping file

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OC-TM concept mapping

Optional step to translate OC concepts to desired TM concepts

A concept mapping file is study specific

Initial effort to create a concept mapping file

A concept mapping file can be reused for subsequent uploads

Unmapped OC concepts are not uploaded

SUBJ_ID SUBJ_ID

Patient Information+Age Subjects+Age

Patient Information+Married

Closing Event+survival time EndPoints+days to death

Closing Event+survival status Endpoints+vital status

.. ..

example OC-TM concept mapping file

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TOC – 1/2 Overview TraIT -> Marinel

Overview deployment:

4 production environments

Sandbox – for study / CRF development

Archive – for closed studies

Acceptance – for technical tests and problem solution

Production

Overview number of studies + short history of OC in the VUmc

AV-stats display

-- bij mij er uit

Integration issues

Dutch legislation

Security / privacy

TTP, Logis, WP3 / WP2, SurfConnext, EHR-systems Make the CTP work also for other work-packages. Could be used as

a hospital-wide ID/HIS/BSN anonymizer. Install as a reverse proxy matching the TraIT urls: www.bmia.nl ; www.openclinica.nl

Illustration with IST / SOLL

Multiple hospitals challanges

Performance

Load balancing

177K study

Multi-threaded

Indices

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TOC – 2/2 Upload

OCDataImporter

MirthConnect / OCWS

Addition of WS-functionality -> Query to retrieve study event status for a singe subject.!!!!!

Performance idea's:

Add multipe TC instances on a single VM and use session-sharing

Or: multiple VM's with 1 single TC instance

TODO's:

Add the graph of the development of number of studies over time

Add a screen shot of AWStats

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