Overview of Estonian opportunities to move towards more personalized medicine with help of Estonian Biobank, national E-Health solutions and state-wide information exchange framework.
Presented at international conference "E-health - integration of IT and medicine" in Tartu 15.09.2013. http://mug.ee/ehealth/
2. Biobanks
• Biobank
– An organized collection of human biological
material and associated information stored for one
or more research purposes
• Population biobank
– The collection has a population basis
– To supply biological materials or data derived
therefrom for multiple future research projects
– It contains biological materials and associated
personal data
3. Genetic research
• Most complex diseases are caused by a large
number of combined effects from genes,
lifestyle, and the environment
• New discoveries and development of tools
depend on studies of large collections of well-
documented, up-to-date epidemiological and
clinical data accompanied by biological
material from individuals
4. Estonian Biobank
• Estonian Genome Center,
University of Tartu
• A prospective, longitudinal,
population biobank with
health record and biological
materials
• Established in 2000
• 52,000 gene donors recruited
-5% of the adult population
• Supported directly by the
government
• Estonian Human Genes
Research Act
6. Data “infrastructure” for
research
• Good quality data collection
– Biomedical data (DNA, plasma, WBC)
– Phenotype
– Genealogy
– Epidemiology data
– Genotypes
• Open to various research projects
• Well defined procedures for data release
• Usable next 30 years
7. Questionnaire of
EGCUT
Personal data
Place of birth
Place of residence
Nationality
Education
Occupation
Genealogy
Parents
Children
Siblings
Grandparents
Health behavior
Smoking and
alcohol
Personality
inventory NEO-
PI-3
Physical activity
EQ-5D
Nutrition
Health self-
assessment
Chronotype
questionnaire
MCTQ
Diseases
Diagnosis
ICD – 10
Treatment
ATC
Psychiatry module
M.I.N.I. and SSP
Questions about
diabetes
Questions
about c/v diseases
Objective data
Height & weight
Blood pressure
Pulse
Handedness
Waist
Hip
8. Diagnoses in the database
(50155 participants)
64245
8928
3106
12677
10766
11833
19918
13833
40209
60778
39490
12585
37322
21170
3352
134
1405
3202
5710
1610
619
0 10000 20000 30000 40000 50000 60000 70000
Certain Infectious And Parasitic Diseases A00-B99
Neoplasms C00-D48
Diseases Of Blood And Blood-Forming Organs And Certain…
Endocrine, Nutritional And Metabolic Diseases E00-E90
Mental, Behavioural Disorders F00-F99
Diseases Of The Nervous System G00-G99
Diseases Of The Eye And Adnexa H00-H59
Diseases Of The Ear And Mastoid Process H60-H95
Diseases Of The Circulatory System I00-I99
Diseases Of The Respiratory System J00-J99
Diseases Of The Digestive System K00-K93
Diseases Of The Skin And Subcutaneous Tissue L00-L99
Diseases Of The Musculoskeletal System And Connective Tissue…
Diseases Of The Genitourinary System N00-N99
Pregnancy, Childbirth And The Puerperium O00-O99
Certain Conditions Originating In The Perinatal Period P00-P96
Congenital Malformations, Deformations, And Chromosomal…
Symptoms, Signs And Abnormal Clinical And Laboratory Findings,…
Injury, Poisoning And Certain Other Consequences Of External…
Factors Influencing Health Status And Contact With Health Services…
External Causes Of Morbidity And Mortality V01-Y98
•In average a participant has
reported 7.8 different diagnoses
•98.3% of participants have
reported at least one disease
9. Education: the Estonian population vs. EGCUT
(50155 participants)
0 10 20 30
Education unknown
No elementary education
Elementary education
Basic education
Secondary education
Professional secondary
education
Higher education
Scientific degree
%
Estonian population EGCUT
10. Using data
• Today’s focus is on Genome
Wide Association Studies
(GWAS)
– "Genetic variants in novel
pathways influence blood
pressure and cardiovascular
disease risk„
– "Complement Factor H
Polymorphism in Age-Related
Macular Degeneration"
– …
• Next focus on rich phenotype,
including health behavior and
sensor data
• Then personalized medicine
solutions
13. Genetic „map“ of Estonia
-0,03
-0,02
-0,01
0
0,01
0,02
0,03
0,04
-0,02 -0,01 0 0,01 0,02 0,03
PC2
PC1
Põhja-Eesti
Lõuna-Eesti
Põhja
Lõuna
14. Secure data handling
Courier
Filled questionnaires
Personal data, health data, genealogy data.
Consent. Transportation code.
Information encrypted.
Consent(paperform).
Biologicalsamples.
Coding center
Memory stick
Consent forms. Questionnaires.
Receptionist
New barcode
High security area Access to database
Scientists
Health data.
No identification
data.
Health data and
identification
data
National Digital Health
Record DB & registries
Operative database
Phenotype database
Data collector IS
Communication server
Laboratory IS
Cryo Preservation – MAPI
Coding center IS
15. Coding challenges
EXTERNAL DATABASES
data collecting
BIOSAMPLES DATA
management
PERSONAL-, GENEALOGY-,
HEALTH DATA
Formatting for integration,
deindentification
DKOOD
I U T L
I
HEALTH DATA
data collecting
I T
PHENOTYPES
integration, quality control,
analysis
U L
CODING CENTRE
H
GENOTYPES
raw data, , quality control,
analysis
U L
PROJECT-BASED RESEARCH
L
CODE RELATIONS
U D L V
genotypes, fenotypes,
biosamples, analysis
D V
BIOSAMPLES DATA
analysis
L
IKOOD UKOOD TKOOD LKOOD VKOOD
FOLLOW UP
coordination
D
FEEDBACK
PERSONALIZED MEDICINE
genotypes, fenotypes,
biosamples, analysis
DATA REALEASE
BIOSAMPLES DATA
logistics
LT
H
HKOOD
D V
D V
16. National Digital Health
Record DB
Online access to
database
Scientists
Health data.
No identification
data
Phenotype database
Patient Portal
National DHR
Cancer Registry
Citizen Registry
Causes of Death Registry
Participant
Participant
Participant
Participant
Participant
Participant
Participant
EGCUT database
Personal health
information
Additional
questions.
Timeline data
Updated
phenotype
data
Participant
Data
release
EGCUT IS 2011-2015
Primary care physician
...
Ver. 5.0
26. Conditions for feedback
• Treatable health conditions with genetic
factors
– Melanoma
– Prostate cancer
– Type I and II Diabetes
– Lupus
– Age-Related Macular Degeneration
– Iron Overload/Hemochromatosis
27. Pharmacogenomics
• How genetic makeup affects an individual’s
response to drugs
• Aim is to ensure maximum efficacy with
minimal adverse effects
• Drugs and drug combinations can be
optimized for each individual's unique genetic
makeup
• Reduces cost of healthcare
28. New devices for self monitoring
• ECG adaptor for
smartphone
• Blood clucose sensors
• Sleep monitoring
• Ultrasound device Vscan
Ref: E. Topol. http://www.ted.com/talks/eric_topol_the_wireless_future_of_medicine.html
29. Challenges and issues
• Awareness doctors and patients
• New technologies and data empower patient with
more possibilities to manage own health
• Ethical issues
– Right to know and right not to know
– Treatable and non-treatable conditions
• Not enough knowledge about associations
between DNA variants and diseases
• Large work-load to keep database of known risk
markers updated
31. Estonian E-services
• 99% of bank
transfers are
performed
electronically
• 94% of income tax
declarations made
via the e-Tax Board
• 24% of votes were
cast over the
internet on 2011
• 62% persons have
completed the e-
census 2012
• 2000: Launch of e-Tax Board
• 2000: Launch of m-Parking
• 2002 : Introduction of national
electronic ID-Card
• 2005: i-Voting was introduced
• 2007: Introduction of m-ID
• 2007: Launch of e-Police
system
• 2008: Launch of e-Health
system
• 2010: Launch of e-Prescription
• 2012: e-census
32. Tools and enablers of
information exchange
• One universal national identification code
– Registries and databases use same code to uniquely
identify persons
• National PKI infrastructure
• The Estonian ID card
– Smartcard with two digital certificates
• National Data Exchange Layer X-Road
• Obligatory national data security framework
• High public acceptance and trust
– No public incidents or misuses (10 years)
34. PHARMACIES AND
FAMILY DOCTORS
2009
X-Road, ID-card, State IS Service Register
HEALTHCAREBOARD
-Healthcareproviders
-Healthprofessionals
-Dispensingchemists
STATEAGENCYOFMEDICINES
-CodingCentre
-Handlersofmedicines
POPULATIONREGISTER
PHARMACIS
2010january
BUSINESSREGISTER
HOSPITALS
2009
FAMILYDOCTORS
2009
SCHOOLNURSES
2010september
EMERGENCYMEDICALSERVICE
2011
NATION- WIDE
HEALTH
INFORMATION
EXCHANGE PLATFORM
2008 december
PRESCRIPTION
CENTRE
2010 january
PATIENT PORTAL
2009
X-ROAD
GATEWAY
SERVICE
2009
35. The Estonian ID card
• The ID card is a mandatory ID document for all
Estonian residents from the age of 15
• Enables secure digital authentication and signing
• A digital signature has the same legal
consequences as a hand-written signature
• Does not have any additional information
– No bank account, no health information etc.
• Active cards: 1 209 594 (13.09.2013)
– Estonian Population 1 286 540 (01.01.2013)
– Estonia has been issuing electronic ID cards from
January 1st 2002
36. Public Key Infrastructure PKI
• PKI or the public key infrastructure enables
secure digital authentication and signing
• The infrastructure also allows forwarding data
by using an encrypting key pair: a public
encryption key and a private decryption key
• In Estonia, this technology is used in relation
with electronic identity (ID card, mobile ID,
digital ID)
• Certification Service and Time-stamping
Service provider is non-governmetal
37. Data Exchange Layer X-Road
• Technical and organizational environment,
which enables secure Internet-based data
exchange between the state’s information
systems
38. Conclusions
• Estonia has great potential to implement state
level personalized medicine solutions
– Genetic research with 5% of population genetic
and continuously updated phenotype information
– Nation wide Health Information Exchange platform
– 10 years of experience of national level e-services
(PKI, X-Road, ID-card, security framework)
– High level public trust and acceptance
Most complex diseases do not stem from a single genetic defect, but are caused by a large number of effects from genetic predisposition, lifestyle, and the environmentThese studies are necessary to work towards improvement of quality of life, more precise disease diagnostics to make progress in personalized medicine.
The following illustrative analyses are made based on the data of 50 155 individuals.
52,000 participants withhealth dataContinuously being updated through follow-up projects and linking to national health registriesOver 1 millionbiologicalsamples 20,000 participants are genotypedwithIlluminamicroarrays120 fullgenomesplus 100 exomes are sequencedNumbersincreasecontinuously
This slide shows the main subsets of the questionnaire. Besidesthe comprehensive health records and objective data alsothe DNA, plasma and WBC samples of each gene donor are deposited in the biobank. 30-50 ml of venous blood are obtained into EDTA Vacutainers which are transported to the central laboratory of EGCUT at +4-6 C within the next 6 to 48h where DNA, plasma and WBC are immediately isolated and kept in aliquots in MAPI straws in liquid N2 for further use.NEO-PI-R TheRevised NEO PersonalityInventory (neopi ai aar)Anatomical Therapeutic Chemical (ATC) Classification System MCTQ Munichchronotypequestionnaire.EQ-5D™ is a standardised instrument for use as a measure of health outcome.The Mini-International NeuropsychiatricInterview (M.I.N.I.) , SSP SwedishUniversitiesScalesofPersonality
In this section of questionnaire, questions about all diseases the donor may suffer will be asked. 45 000 GD andmed: 1.3% (599) of gene donors have confirmed that they don’t have any diseases. 0.4% (167) of donors are neither aware of the diseases he/she might have and nor confirm not having it. 98.3% of individuals have suffered or suffers from different diseases. Altogether, 44 354 GDs have 344 187 diagnoses, in average 7.8 diagnoses per donor.In average, a GD hasreported ca 8 different diagnoses. Mostfrequently infectious diseases, diseases of respiratory system and circulatory system are mentioned.
Several essential changes occurred in the education of Estonia since the 20s and till the end of the last century. The duration of programs, names and contents of levels of study changed. They were divided according to the detailed classification of educational sublevels as follows:higher educationprofessional secondary education after secondary educationprofessional secondary education after basic educationvocational secondary education after secondary educationvocational secondary educationgeneral secondary educationbasic educationelementary educationno elementary educationAmong GDs, there are more individuals with higher (18%) and professional secondary (33.3%) education. Fewer individuals have elementary (15.8%) and no elementary (2.8%) education. In the whole population, there are more females with higher and more males with elementary education. The same ratio is represented among GDsAnaveragegenedonorisquitewell-educated and has at leastgraduatedfromhighschool (gymnasium) orvocationalschool.
Erinevaid haiguseid on enam kui 12 000, samas kindlaid seoseid DNA mustrite ja haiguste vahel teada veel suhteliselt vähe.
Projekti ENGAGE raamesEesti doonoreid 1026
Ongoing linking on a regular basisMedical registries (Causes of Death, Cancer, TBC, Population Register) 2372 participants have died as of August 2013 Linking approved by the Ethics Committee and the Data Protection InspectionEstonian e-health database Estonian Health Insurance Fund databaseinc. digital prescriptions database Databases of the two largest 3rd level hospitals (currently we have two: Tartu University Hospital and North Estonia Medical Centre in Tallinn) Estonia has good solutions to update phenotype data from various national registriries and databases.Additionally is EGCUT actively collecting additional information from previously recruited participants.In 2013 there will be first solutions to feedback personal health information (primarly related to genetic information) to patient and primary care physicians.
Personalized medicine or PM is a medical model that proposes the customization of healthcare - with medical decisions, practices, and/or products being tailored to the individual patient. The use of genetic information has played a major role in certain aspects of personalized medicine, and the term was even first coined in the context of genetics (though it has since broadened to encompass all sorts of personalization measures). To distinguish from the sense in which medicine has always been inherently "personal" to each patient, PM commonly denotes the use of some kind of technology or discovery enabling a level of personalization not previously feasible or practical.
Electrocardiography (ECG or EKG from Greek: kardia, meaning heart) is a transthoracic (across the thorax or chest) interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the surface of the skin and recorded by a device external to the body.[1] The recording produced by this noninvasive procedure is termed an electrocardiogram (also ECG or EKG).