A presentation delivered by Dipak Kalra at the 2019 IPPOSI Conference on Electronic Health Records.

1. Electronic Health Records for Clinical Research
EHRS FOR CLINICAL
RESEARCH
Professor Dipak Kalra
President of i~HD
IPPOSI Annual Conference, Dublin
7th October 2019

2. By learning from its data…
▪ …Kaiser Permanente is able to track outcomes and develop data
driven algorithms embedded within its EHR systems, to achieve:
▪ HIV death rate half of US national average
▪ Decrease in coronary heart disease death rate by a third
▪ Decrease in pressure ulcers by two thirds
▪ Death due to sepsis reduced by > 50%
2

3. Multi-morbidity: the scale of the challenge
3
Chris Salisbury, Leigh Johnson, Sarah Purdy, Jose M Valderas and Alan A Montgomery
Br J Gen Pract 2011; 61 (582): e12-e21

4. 4
> 3x variation in death
during first HF admission
3x variation in 12 week
mortality rate for HF
>4x variation in 12 week
readmission rate for HF
12
17
21
21
26
28
28
29
31
36
36
36
37
41
41
54
0 10 20 30 40 50 60
12 week readmission rate, %
Finland
Austria
Sweden
France
Netherlands
Germany
Ireland
UK
Denmark
Israel
Switzerland
Spain
Italy
Hungary
Greece
Poland
x 4.5
6
9
10
11
12
12
12
14
14
15
16
16
16
18
19
19
0 5 10 15 20
12 week mortality rate, %
Austria
Spain
Finland
Switzerland
France
UK
Sweden
Ireland
Netherlands
Greece
Denmark
x 3
Italy
Poland
Israel
Hungary
Germany2.9
3.5
3.8
3.9
3.9
5.6
6.9
7.3
7.6
7.8
9.1
9.5
9.6
9.9
9.9
10.2
0 2 4 6 8 10 12
Finland
UK
Poland
France
Greece
Netherlands
Denmark
Germany
Israel
Italy
Sweden
x 3.5
Ireland
Death during first admission, %
Austria
Switzerland
Spain
Hungary
Variation of heart failure outcomes across European countries
Slide courtesy of Thomas Allvin, EFPIA

5. The Learning Health System: “Virtuous Cycles” of Study and Change
5
Take Action
Interpret Results
Analyze Data Design
Intervention
Assemble Data
Capture Practice
as Data
Formation of
Learning
Community
Slide courtesy of Prof Charles P. Friedman, Department of Learning Health Sciences, University of Michigan

6. The LHS ambitions of many European healthcare providers
▪ Shift the focus of performance and reward from activity to outcomes
▪ Optimise care pathways to maximise health outcomes whist making
best use of resources
▪ Respond to payer and public demands for more integrated and person
centred care
▪ Implement continuous learning and improvement cycles
▪ Enhance their culture and capability to undertake research, for
reputation and business reasons
▪ Collaborate across hospital networks, and across Europe, to share
good practices and support each other with improvement
6

7. RWE opportunities for life sciences and medicines
development
▪ Quantify disease diversity and unmet treatment needs
▪ Biomarker discovery and validation
▪ Quantify deeply-stratified populations, for targeted therapies
▪ Accelerate the conduct of clinical trials
▪ Outcomes research, comparative effectiveness research
▪ Safety signal detection and validation
▪ New treatment indication areas
▪ Adaptive trials and licensing
▪ Evidence to underpin value based health care models
▪ Collaborate to maximise health outcomes
7

8. The EHR4CR project
▪ EHR4CR – Electronic Health Records for Clinical Research
▪ 4+1 year project (2011-2016), 35 partners, budget >17M€
▪ The mission
▪ Provide a platform for trustworthy re-use of EHR data to support innovation
in clinical research and healthcare operations
▪ The outcome
▪ A platform connecting securely to the data within multiple hospital EHR systems:
▪ predict the number of eligible patients for a candidate clinical trial protocol
▪ assess its feasibility and to locate the most relevant hospital sites
▪ efficiently identify and contact the patients who may be eligible for particular clinical trials
▪ A not for profit institute to drive the success conditions for multi-stakeholder benefits from health data:
i~HD
8

9. InSite – Technical Overview, for Protocol feasibility
9
…
EHR CDW
InSite
Local Install
ETL Central
Platform
Only aggregated data
(patient counts) leave
the hospital,
only on approval
InSite provides expertise
and tools to support
local sites with mappings
Local InSite
applications to
support recruitment
Secure access
for researchers
Protected by Privacy
Enhancing Techniques
e.g. suppression of small
counts
Full audit trail inside hospital
External governance by i~HD

10. InSite – Protocol feasibility query
10

11. Electronic Health Records for Clinical Research 11
Confirming public acceptance
▪ High percentage of respondents were in favour of re-using EHR
data for research

12. Discoveries from >1m patient clinical data repositories
▪ Validating >200 novel biomarkers predicting cardiovascular risk
▪ Investigating variation of 174,000 observed national prescribing
patterns to national guidelines for COPD
▪ Comparing ~8,000 treatment outcomes for leukaemia by age:
uncovering a major unmet treatment need
▪ Developing new cancer risk stratification algorithms by mining >700
million records
12

13. 13
THE EHDEN FEDERATED DATA NETWORK
A
R
A
C
H
N
E
Analysis query
Aggregated results
EMR
LIMS
Rx
Dx
Admin
…
A
R
A
C
H
N
E
Local
Database
OMOP
Database
Local Governance
EMR
LIMS
Rx
Dx
Admin
…
A
R
A
C
H
N
E
Local
Database
OMOP
Database
Local Governance
EMR
LIMS
Rx
Dx
Admin
…
A
R
A
C
H
N
E
Local
Database
OMOP
Database
Local Governance
ATLAS
Many different open source
tools (cohort builder,
estimation, incidence rate, ….)
EHDEN will develop new tools
and dashboards.
The EHDEN platform
Slide from Nigel Hughes, Janssen, IMI EHDEN project

14. The German Medical Informatics Initiative
Goals
Innovative IT solutions to improve research & patient care
▪ starting at university hospitals & extending to smaller sites
Intensify the exchange and sharing of data
▪ between research and the health care delivery system
Re-establish medical informatics as a progressive field
▪ in research, teaching and continuing education
Set up data integration centers (DIC)
▪ to pool local data resources and network with other sites
14
Slide from Thomas Ganslandt, MIRACUM: Sharing Data for a Learning Health System

15. There is now a convergence of opportunity from
health data
Need to collaborate to improve access to combined
health data from multiple sources
Clinical Research
• Conduct faster, more efficient, clinical
research
• Demonstrate the benefit from
innovative products
• Create better Real World Evidence
• Generate new evidence for precision
medicine and value based models
Healthcare
• Improve quality, safety and
connectedness of care
• Empower patients in self-care and
health maintenance
• Use outcomes to improve services
• Have better evidence for public health
strategies
15

16. 16
Citizen and
patient
associations
Clinical and
biomedical
research
companies
Health data
aggregators
and analytics
companies
ICT
companies,
standards
developers
Scientific
centres,
Reference
Networks
Health system
funders, care
commissioners
Multi-national
decision
makers
Healthcare
providers and
provider
organisations
to co-create solutions for:
• the capture and sharing
of better quality health
data
• its trustworthy use for
smarter health care and
efficient research
i~HD is a neutral body, bringing stakeholders together

17. Promoting multi-stakeholder engagement in
standards profiling and adoption
17
Clinician and patient involvement
Technical
specifications
Clinical
specifications
Slide courtesy of Robert Vander Stichele
modelling, terminology, ontology
& workflow representations
to produce harmonised semantic
resources
Research and public health involvement

18. Data quality dimensions
and assessment methods
❑ Many different data quality indicators can be used
❑ Several published definitions for the same concept, which we needed to
formalise
Mapping exercise
Prioritisation with hospitals
9 data quality dimensions
adopted
Completeness Consistency Correctness
Uniqueness Timeliness Stability
Relevance Contextualization Trustworthiness

19. Extracts from a sample i~HD DQ assessment
19

20. Assuring trust when reusing EHRs for research
▪ Compliance with data protection legislation, at a European level and
across all Member States
▪ Consistent information governance expectations across Europe
▪ Societally acceptable codes of practice for governing the reuse of health data
▪ Well-adopted state of the art in privacy protection and information security
▪ Greater societal support for health and research uses of health data
▪ A scaling up of learning from health data, leading to more rapid
innovation in treatments, and accelerated health system transformation
towards better health outcomes
20

21. Citizens juries
▪ https://www.connectedhealthcities.org/get-involved/citizens-juries/
21Slide courtesy of Mary Tully, Director of Public Engagement
CHC, University of Manchester

22. 22

23. Demonstrating value from the use of health data
23
Showcase the benefits of using health data
on a large scale:
• outcomes evidence to improve care
• faster and more efficient clinical research
• stronger evidence for public health strategy
• patient empowerment for better health
Value
to healthcare
Value to patients and
to society
Value
to research
Grow a Network
of Excellence
Promote our
mission and
collaborate globally
enabling the Learning Health (eco)System