Joining up clinical care and Joining up clinical care and biomedical researchbiomedical research

CLEF/CLEF/

CLEF-ServicesCLEF-Services

Alan Rector et al.Alan Rector et al.rector@cs.man.ac.ukrector@cs.man.ac.uk

www.clinical-escience.orgwww.clinical-escience.org

A Convergence of NeedA Convergence of Need

Post genomic research

more & better more & better clinical clinical

informationinformation

Clinical Practice, Audit &

Governance

National Policyfor IT (NPfIT)

Evidence based

health care

Clinical trials recruitment & support

Patient Care Cycle

Trials & Research Cycle

Making itMaking itWorkWork

ExtractInformation

Integrate &Aggregate

(provenance)

Construct‘Chronicle’(inference)

Individual Summaries& Queries

Depersonalisetext

PseudonymiseIn Hospital

ReidentifyBy Hospital(if agreed)

Chronicle

PseudonymisedRepository Ethical oversight

committee

FormulateQueries

Knowledgeenrichment

(workflows+)Hazard

Monitoring

StatisticalDisclosure

Control

The repository so far: The repository so far: 20,000 patients, 20,000 patients,

1.7 million EHR nodes, 1.7 million EHR nodes, 880,000 data values880,000 data values 365,000 narratives, 365,000 narratives,

ready for Information Extractionready for Information Extraction

“…located in the lower or middle lobe of the lung..”

Location of the tumour is not held in structured form: it is only found consistently in the narrative of radiology

reports

IE and the Chronicle are needed to IE and the Chronicle are needed to enrich the original structured dataenrich the original structured data

The coded data are not sufficient to The coded data are not sufficient to meet the needs of research queries:meet the needs of research queries:

Information ExtractionInformation Extraction

InformationExtraction

Engine

…There is a lobulated mass adjacent to suture material in the right lower zone.…

Chest 8/5/96

…Once again numerous nodules are seen in the right lower lobe.…

Chest 30/5/96

…A further new lung nodule is seen in the left upper zone.…

Chest 6/8/97

Date: 8/5/96Sign-1:

Name: massLocus-1:

Name: lower zoneLocation-1:

Sign: Sign-1Locus: Locus-1

Date: 30/5/96Sign-2:

Name: nodulesLocus-2:

Name: lower lobeLocation-2:

Sign: Sign-2Locus: Locus-2

Date: 6/8/97Sign-3:

Name: lung noduleLocus-3:

Name: upper zoneLocation-3:

Sign: Sign-3Locus: Locus-3

Information IntegrationInformation Integration

Chronicler

Date: 30/5/96Sign-2:

Name: nodulesLocus-2:

Name: lower lobeLocation-2:

Sign: Sign-2Locus: Locus-2

Date: 8/5/96Sign-1:

Name: massLocus-1:

Name: lower zoneLocation-1:

Sign: Sign-1Locus: Locus-1

Date: 6/8/97Sign-3:

Name: lung noduleLocus-3:

Name: upper zoneLocation-3:

Sign: Sign-3Locus: Locus-3

Problem:Name: lung cancerLocation: lower lobe of lung

ICD-O-T code: C34.3

CLEF WYSIWYM Query Writer – L2Login Query OMIM Exit

Relevant Subjects

Treatment Profiles

Outcome Measures

Patients with [this type of tumour] at [this site]

Percentage of patients in [this condition] after [this interval of time].

Patients who received [this type of treatment], compared with patients who received [this type of treatment]. 

AND [another characteristic].

For communities ofFor communities of biomedical E-Scientists:biomedical E-Scientists: Safe &Safe & easy analysis easy analysis

e-Scientists use query writer

Percentage of patients [alive] after [1 year] and after [2 years] and after [5 years].

Patients who received [radiotherapy] [daily], compared with patients who received [radiotherapy] [every other day] and those who received [no radiotherapy]. 

AND [BRCA1 (OMIM 113705)].Patients with [adenocarcinoma] at [this site]bladder

bloodbrainbreastcervixcolonendometriumkidneylarynxlunglymphnodeoesophagusovarypancreasprostaterectumskinstomachtestistongue

Patients with [adenocarcinoma] of [this laterality] of [this part] of [breast]

…or graphically

For all patients with adenocarcinoma of the breast, compare the survival at 1, 2 and 5 years for those patients who had daily radiotherapy, those who had radiotherapy on alternate days, and those who had no radiotherapy

Feedback TextQUERY RESULT1792 patients diagnosed with adenocarcinoma of the breast were found. 788 had radiotherapy daily, 513 had it on alternate days and 491 had no radiotherapy.

After 5 years, 20% (n=158) of patients who had a daily treatment were alive. After 5 years, 10% (n=49) who had alternate day treatment were alive. After 5 years, 5% (n=27) of the patients who had no treatment were alive.

Result of running query displayed as generated text…

Generated text confirms the nature of the query

SubmitSubmit

monitored for risk of reidentification

SAFE

AND [this genetic marker].

Links out to other bioscience resources e.g. OMIM, PubMed, Gene Ontology

Query construction: Query construction: specifying the age rangespecifying the age range

Query construction: Query construction: selecting a cancer tissue diagnosisselecting a cancer tissue diagnosis

The final query: The final query: ready to submit to the repository query ready to submit to the repository query

serviceservice

1975 1980 1985 1990 1995 2000

DiedGrade III infiltrating

ductal carcinoma left breast

NodesLiverSpleenKidneyBone

NodesLiverSpleenKidneyBone

T1>N1>M0

T1N3cM0

T1>N3cM1

>Stage IIA Stage IIIc Stage IV

SSSSSSS S S SS SSStaging CT

RRecurrence

R R R

TAMOXIFEN ARIMIDEX

RADIO

CHEMO

Visualisation of Chronicle: Visualisation of Chronicle: A A timeline of index eventstimeline of index events

CLEF ChronicleCLEF Chronicle• Inferred “best view” of what is known about a

patient– What was done and why?– What happened and why?

• Includes detailed provenance - sources & inferences

• Enriched by information on analyses, conclusions, workflows, related searches, etc.

• Workflows

• Designed for scalable retrieval, aggregation, and alignment– Simulations and real data for testing of alternatives

• Virtual view of EHR ... or ...• Persistent network using Semantic Web/Grid Technology ...or...• Temporal DB

A CLEF ChronicleA CLEF ChroniclePatient:1382

Mass:1666

locus

Pain:5735

locus

Radio:1812

plansplans

Chemo:6502

plans

treats

treats

locus

target

attends

attendsattends

Ulcer:1945

finding

Cancer:1914

finding

Breast:1492

locus

Clinic:4096

Biopsy:1066

Clinic:1024plans Clinic:2010

about

PATIENT

CONSULT

INTERVENTION

PROBLEM

PATHOLOGY

LOCUS

Other Feature

Clinical Course

Presence / absence

Status

GoalINVESTIGATION

recommend finding

Status

Evidence for

Sex

Age

GeneticProfile

Diagnostic Status

DRUG

REGIMEN

target

Size

treat

s/in

dica

tes

about

compare

has-locus

involvessubpart

causes

indi

cate

dBy

causes

has-locus

after

has-locusre

com

men

d

indication

Time

SchemaSchema

GeneticGenomicImaging…

Personal data Privacy:Personal data Privacy:Policy and Legal LevelPolicy and Legal Level

• in the UK– Common Law of Confidentiality– Data Protection Act 1998– Human Rights Act 1998– Section 60 of Heath & Social Care Act 2001– BMA Guidance Oct 1999– GMC Guidance Sept 2000

– at a European Level– European Community Directive 95/46/EC (1995)– Council of Europe Recommendation R(97)5

(1997)

Personal data PrivacyPersonal data Privacy

• The UK Data Protection Act defines "personal data" as:– "data which relate to a living individual who can be

identified (a) from those data, or (b) from those data and other information which is in the possession of, or is likely to come into the possession of, the data controller“

• This is likely to apply to any clinically useful information about living patients

• Patient consent would be required for CLEF to acquire the data into its repository, and for each new kind of research access to the data– This is not scalable

Anonymised data PrivacyAnonymised data Privacy

• If legitimately processed for research or statistical purposes,

“can be kept indefinitely and are exempt from the subject access rights if the results of the work are not made available in a form from which data subjects can be identified”

• If CLEF could make sure the data is anonymous, consent would not be required and the data could be used for any reasonable research purpose– This is the only scalable approach

• But.. no anonymisation can be perfect

Socio-Technical Response: Socio-Technical Response: brief summarybrief summary

1) De-identify the data– make overt identifying data unusable

– Several layers of pseudonymisation– No source should be able to generate or obtain a central CLEF ID – CLEF should never be able to get to source IDs

– Collaborating with e-science/Grid projects , BioBank, NHS,...

2) De-personalise the parts of the record which risk re-identifying the data

– depersonalising text requires specialised tools

3) Still treat the data as having some small potential risk of re-identification

– regulate, restrict and monitor access – FAME-Permis– statistical disclosure control

• Cathie Marsh Centre for Census and Survey Research

CLEF to CLEF-Services CLEF to CLEF-Services from development to usefrom development to use

• Trials: Initially– Institute of Genetic Medicine, London

collaboration sponsored by the London Development Agency

• Close links to Clinical Trials Centres - MRC / UCL / CRUK – Genetic effects on outcome and treatment response

• Start with cancer, but ...– Aim for re-use in cardiovascular disease, mental health,

diabetes...

– Trialists and statisticians• New forms of data require new forms of analysis

• Technical deployment: build – An E-Science/Grid environment

• Collaborative and collection based research• Re-usable components within a Grid Services

architecture• Build on and extend myGrid• Collaborate with CaGrid, PsyGrid, eDiamond, ...

To link Grid & NHS computingTo link Grid & NHS computingNHS Information (NPfIT) Research Information

genetics

biosciences

clinical trials and longitudinal studies

knowledge management

decision support

data mining

health improvement

patient centred medicine

clinical service framework

clinical governance

outcome: effectiveness/ efficiency

evidence

Information forpatients & public

To realise the research potential of To realise the research potential of the nhsthe nhs

SecurityImages, Language, Genomics

Architecture, Web/Grid Services, Terminology, Standards

Software componentsSoftware componentsSteps towards wide deployment Steps towards wide deployment

• Reducing the effort of re-use• Common services & standards for...

– Language technology – Repositories– Chronicles– Workbench analysis and workflows

• Build on myGrid & other E-Science / Grid efforts

– Knowledge resource management as Grid Services

• Build on CO-ODE/HyOntUse

The key is collaborationThe key is collaboration• Post-genomic research & cancer

– NCRI – designed to fill gaps in planning matrix• NTRAC/NCTR, NCRN, CaGrid, eDiamond

– PsyGrid– BioBank

• NHS, DoH and Industry– DTI – Funding for linkage to industry and NHS

• International– US NCICB, Mouse/Human Anatomy projects– Cancer Networks & National Programme

• E-Science & Standards– myGrid, CO-ODE/HyOntUse, ESNW, Semantic Web/Grid,...– HL7, CEN TC251, ISO TC215– Semantic Mining NoE in 6th Framework

• Bioinformatics– OBO (GO, GONG, MGED), EBI, SAEL, ...

CLEF ConsortiumCLEF Consortium• Clinical

– Royal Marsden Hospital Trust– London Institute for Genetic Medicine– North and North Central London Cancer Networks

• Technical and E-Science– University of Manchester (E-Science & knowledge)

• Biohealth Information Forum – link to myGrid• Cathie Marsh Centre for Census and Social Statistics• E-Science Centre including link to Security projects (FAME-Permis)

– University College London (Electronic Health Records)• Centre for Health Informatics and Multiprofessional Education• E-Science Centre including link to Security projects

– University of Sheffield (Language technology)• Natural Language Group, Department of Computer Science

– Cambridge University (Privacy and policy)• Judge Institute for Management Studies,

– University of Brighton (Language technology and HCI)• Information Technology Research Institute,

• Clinical and Industrial/NHS steering committees– DTI Funded companion project

www.clinical-escience.orgwww.clinical-escience.org

CLEF/CLEF-SERVICESCLEF/CLEF-SERVICES

Empowering the e-Clinical ResearchEmpowering the e-Clinical ResearchMaking new research possibleMaking new research possible

Making existing research more effectiveMaking existing research more effective

byby

Removing barriers to data sharingRemoving barriers to data sharingJoining up health care and biomedical researchJoining up health care and biomedical research

Re-usable components for clinical e-scienceRe-usable components for clinical e-science