Grid Based Clinical Trial Scenarios
Dr Richard Sinnott
Technical Director National e-Science Centre
|||
Deputy Director Technical Bioinformatics
Research Centre
University of Glasgow
ros@dcs.gla.ac.uk
22nd September 2004
LSG-RG GGF-12,
22 Sep 2004
NeSC in the UK
Transition to OGSI/OGSA under discussion
NeSC
HPC(x)
Two
UK OGSA
Gride-Science
projects started
in January
Previous
workTest
on UK
Grid based
on GT2
UCL, Imperial College, Universities of Edinburgh and Newcastle Glasgow
Demonstrated broad set of applications across it
X
Universities of Portsmouth, Reading, Manchester, Westminster and CCLRC
X
Monte Carlo simulations of ionic diffusion through
radiation damaged crystal structures
The next Grid
X
Integrated Earth system modelling
Belfast
software
X
BLAST on the Grid
X
Grid Integration Test Script Suite
X
…
X
Challenges/
There are still issues to be
resolved
Opportunities
OGSA definition and delivery
?
X
X
Standards OGSI,
WSRF, …
…and Technologies GT3,
GT4…
Daresbury Lab
Edinburgh
Newcastle
White Rose Grid
ManchesterGrid Service
Core National
Hosting environments & Platforms
CSAR Oxford
Combinations of services supported
RAL
Cardiff
Material and grids to support adopters
Cambridge
Hinxton
London
Southampton
LSG-RG GGF-12,
22 Sep 2004
Overview
Context of clinical trials challenges/requirements
Overview of Virtual Organisations for Trials and
Epidemiological Studies (VOTES) project
Scenarios to be supported
Initial thoughts on Grid usage
Future Plans
LSG-RG GGF-12,
22 Sep 2004
Clinical Trials Background
Reliable assessment of moderate effects of treatment of important diseases
(e.g. cancer) requires studies that guarantee
strict control of bias (requiring randomization and analysis)
strict control of random error
Up to date information on patterns of disease/frequency of clinical
procedures can help inform the design of a clinical trial
enable appropriate strategies for rapid and efficient recruitment to be devised
Generating this evidence typically requires the collection of data on many
thousands of people over a period of several years.
essential to avoid misleading results caused by the play of chance
Clinical trials usually require collaborative effort
data are collected from individuals and from existing health records
from multiple investigative sites
Study progress, data quality, analysis of results managed by one or more
coordinating centres
LSG-RG GGF-12,
22 Sep 2004
Clinical Trials Demands
Need to answer questions such as
How many men in Scotland between the ages of 4565 had a heart attack in the last 5 years? Of those that
did, which of those men took drug X? Did those taking
drug X suffer any further major events?
Also eventually would like to be able to answer
questions like,
X
is the high rate of heart attacks in Scotland caused by genetic
factors
– ( …or love for deep fried Mars Bars!!!)
LSG-RG GGF-12,
22 Sep 2004
Clinical Trials Requirements
Need to ensure
Ethical and legal factors considered
X
Patient consent for the data to be made available
Right people seeing right data and in right context
In moving data from site A to site C can it go via site
B?
Right services made available
X
For finding, accessing, querying, analysing data…
– Note general publish model mostly not possible
Provenance of data
X
Where did it come from, how was it generated, has it been
validated, …
LSG-RG GGF-12,
22 Sep 2004
VOTES
Virtual Organisations for Trials and Epidemiological Studies
3 year (£2.8M) MRC funded project expected to start imminently
Plans to develop framework for producing Grid infrastructures to
address key components of clinical trial/observational study
X
X
X
Recruitment of potentially eligible participants
Data collection during the study
Study administration and coordination
– Involves Glasgow, Oxford, Leicester, Nottingham, Manchester, Imperial
Clinical Virtual Organisation Framework
Used to realise
CVO-1
(e.g. for data
collection)
CVO-2
(e.g. for
recruitment)
LeiNott
GLA
Disease
registries
Hospital
databases
Transfer
Grid
GPs
OX
IMP
Clinical trial
data sets
LSG-RG GGF-12,
22 Sep 2004
VOTES Goals
Recruitment of potentially eligible participants
Major limiting step in clinical trials
– Avoid sending out 200,000 letters inviting people to enter trial
» Better to focus on specific target groups
» Ideally deal with patients who have given consent
X
Information is available electronically (in various DBs) therefore should in principle
be able to access and use it
– … but clinical data sets owned by variety of organisations?
– existing approaches at access and using these data sets cumbersome
» e.g. clinical trials officer physically taking laptop to NHS office and querying DB
whilst being monitored,
» … data sets deleted once statistics recorded
LSG-RG GGF-12,
22 Sep 2004
VOTES Goals
Data collection during the study
Increased usage of direct data entry systems
X
X
reduced need for extensive checks against paper case report forms
improves quality of data
– automated checks during the interview
» e.g. range checks, consistency within and between forms, eligibility for randomization
Also in many clinical research settings, internet access not always available
when clinician interviewing a study participant
X
e.g. whilst on hospital ward
Need remote data entry systems for large-scale studies to be portable
X
Should support offline functionality where data transferred intermittently to and from the study
databases
Should support rapid tailoring to meet requirements of new trials or
observational studies
LSG-RG GGF-12,
22 Sep 2004
VOTES Goals
Study Management
Traditionally study data held on a central computer database and, as a
consequence, remote access to live data substantially limited
X
Better to have web (GRID)-based applications to facilitate more flexible coordination of
large-scale studies
– allow multiple users to have access to data and functions appropriate to their role in
the study
» should allow for fine grained authorisation…
X
X
X
X
X
Should support access to relevant up-to-date information to others involved in the study
– e.g. Steering Committee or the Data Monitoring Committee
Allow to log details of essential documents such as ethics and regulatory approvals
– support rapid dissemination of study documentation such as changes to protocol
Support coordinated transport of study treatment and collection of study samples
– allow authorised study clinicians to review relevant data on individual study
participants, including case report forms, blood results, and serious adverse events
Should provide current information about trials activity,
– reports on the number of records screened, invitations produced, …
Will allow study coordinators to identify and address barriers to recruitment at early stage
LSG-RG GGF-12,
22 Sep 2004
System Scenario for Patient
Identification & Recruitment via GPs
GPASS
with
Private
Data Sets
Check signature
If ok run XML
search against GP
DB using, e.g. XML
search capability for
GPASS
(EMIS/VAMP)
GPASS pulls other
data, e.g. from SCI
store?
Patients
consent?
Forms auto
completed and
results to portal
to consenting
patients
Trials coordinator
(secure/authorised log-in)
Portal has details of all GPs, … or
can establish this someway? (SCI
store for GP Code, GP Practice
Code, CHI etc)
Trials Portal
Personalised
Services
Follow link with Trial
Trial Trial
X.509 cert’s in #1
#2
#3
browsers
Authentication,
GP Decides to download
authorisation
signed XML pro-forma
for Trial #1
Pre-designed for specific VO…
trials / protocols
Mostly completed (trial
criteria fields) – contain
patient matching criteria
Link in to data
collection/analysis work
OGSA-DAI
Automatically produce
letters for matching patients
e.g. using SCI Discharge
GP
with
browser
SCI Gateway
Need to get
certificates issued
for local GPs and
tell them how to
get them into
browsers etc
Email describes
nature of trial,
things to do to
participate, other
info ($) has link
to secure web
service (Trial #1)
LSG-RG GGF-12,
22 Sep 2004
All comms through SCI
Gateway
Relevant trial information added to
secure repository – to be used with
other Grid services (for stats, etc …)
Important to get meta-data too for
provenance etc
Secure Data
Repository
Work Required
Portal development
Security aspects
Web services for patient identification, data validity checking, …
Workflows for cross checking various resources, e.g. death register,
cancer register, with hospital records, GPASS info, … etc
Engineer trial forms
Link to coding resources, e.g. WHO medications ontology, MedRA for
adverse event information, …
Should capture protocol information and data sets required
Designing XML queries
Conform to existing schemas for NHS Scotland
Should capture criteria for patient matching for specific trials
Establish Secure Repository for Trials
Basis for overall trials, history, provenance, record linkage, …
Establish procedures (use existing ones?) for meta-data collection
X
Links to data annotation/provenance activities of NDCC
LSG-RG GGF-12,
22 Sep 2004
Grid Security
OGSA security
Single sign-on based on (X.509) digital certificates
X
establish credentials
– Certification authority based (RAL in UK)
Services (and clients) have APIs for fine grained security
X
Based on GSS-API
Provides for authentication but need authorisation
X
Various technologies for authorisation including PERMIS, CAS, …
Collaborating with PrivilEge and Role Management
Infrastructure Standards Validation (PERMIS) team
X
Lead by Prof David Chadwick, University of Salford
– (www.permis.org)
LSG-RG GGF-12,
22 Sep 2004
Security Authorisation
PERMIS allows to
Define roles for who can do what on what
X
Policy = { Role x Target x Action }
– Can user X invoke service Y and access or change data Z?
» Policies created with PERMIS PolicyEditor (output is XML based policy)
LSG-RG GGF-12,
22 Sep 2004
Security Authorisation
PERMIS Privilege Allocator then used to sign policies
Associates roles with specific users
X
Policies stored as attribute certificates in LDAP server
When is authorisation done?
Two main choices
X
X
Portal personalised for users based on their policies
– If not allowed to invoke service then they do not get to see it
Actions of users (with given role) are authorised every time the service is invoked
– They can see the service but potentially not be allowed to invoke it
» Performance issues… but more likely scenario for authorisation
X
In both cases, if not explicitly agreed in policy then rejected and logged!
– Both cases to be explored
Use of the GGF SAML AuthZ specification
X
Already investigated in BRIDGES project
– Identified issues with standards
LSG-RG GGF-12,
22 Sep 2004
Future Plans
Accessing and using clinical trials data only the
start
Ideally want to link these data sets to numerous others to
support
X
X
Systems biology
Wider e-Health initiatives
Genetics Healthcare Initiative proposal recently
submitted to Chief Scientists Office plans to do exactly
this across Scotland
LSG-RG GGF-12,
22 Sep 2004
LSG-RG GGF-12,
22 Sep 2004
+ links to plant/crops,
environmental, health, …
information sources
Populations
Organisms
Physiology
Organs
Tissues
Cell signalling
Cell
Protein-protein interaction (pathways)
Protein functions
Protein Structures
Gene expressions
Nucleotide structures
Nucleotide sequences
The Grid Enabled Bio-Data Future
Bridges Project
C F G V ir t u a l
P u b lic a lly C u r a te d D a t a
E nsem bl
O r g a n is a t io n
O M IM
G la s g o w
S W I S S -P R O T
P riv a te
E d in b u r g h
MGI
VO Authorisation
P r iv a te
d ata
O x fo rd
d ata
Information
Integrator
…
RGD
L e ic e s te r
D ATA
HUB
P r iv a te
d ata
N e th e rla n d s
OGSA-DAI
bl a
st
Synteny
Grid
Service
P riv a te
data
HUGO
P r iv a te
data
London
P riv a te
d ata
+
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22 Sep 2004
Bridges Portal
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22 Sep 2004
MagnaVista
www.nesc.ac.uk
LSG-RG GGF-12,
22 Sep 2004
MagnaVista
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22 Sep 2004
QTL upload
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22 Sep 2004
QTL upload
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22 Sep 2004
QTL browsing
LSG-RG GGF-12,
22 Sep 2004
Grid Blast Client
• Allows
‘genome scale’
blasting
• Uses ScotGrid and idle
compute resources of
training lab Condor pool
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22 Sep 2004
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22 Sep 2004
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22 Sep 2004
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22 Sep 2004
DyVOSE Project
Dynamic Virtual Organisations for e-Science Education
project
Two year project started 1st May 2004 funded by JISC
Exploring advanced authorisation infrastructures for security
X
… in Grid Computing Module as part of advanced MSc at Glasgow
– Will provide insight into rolling Grid out to the masses!
ScotGrid
GU Condor pool
Other (known!)
Grid resources
Education
VO policies
PERMIS based
Authorisation checks
Authorisation decisions
LSG-RG GGF-12,
22 Sep 2004
Scottish Bioinformatics Research Network
Four year proposal (£2.4M) expected to start November
2004
Funded by Scottish Enterprise, Scottish Higher Education Funding
Council, Scottish Executive Environment and Rural Affairs
Department
X
Involves Glasgow, Dundee, Edinburgh, Scottish Bioinformatics Forum
Aim to provide bioinformatics infrastructure for Scottish health,
agriculture and industry
X
X
X
Infrastructure support at Dundee, Edinburgh and Glasgow to support first-rate
research in bioinformatics at each academic institute
Infrastructure support at three institutes, to support inter-institutional sharing of
compute and data resources through application of Grid computing
Outreach and training activities mediated by the Scottish Bioinformatics Forum
LSG-RG GGF-12,
22 Sep 2004
Conclusions
NeSC Glasgow focussed largely on life sciences and security
The GRID is happening and will influence life sciences
Government SR allocated £115M for eScience
Life sciences are key target areas for eScience
Grid middleware and standards still “evolving“
Non-trivial learning curve, immaturity of technology
Security absolutely needs to be addressed by middleware developers
AND educators
Real explorations essential to inform wider standards developers
GGF, OASIS, IETF, W3C, ....
and middleware producers
LSG-RG GGF-12,
22 Sep 2004
Conclusions
Main take home message:
need coordination of
X
X
GRID software engineering/standards
Life science needs/standards
Without this, metaphor of electric power GRID doomed
LSG-RG GGF-12,
22 Sep 2004