How Registries can be used to improve trans-national care
Initial Funding
FP6, 100,000 Euros
per annum
Post FP6
Follow up support:
100,000 Euros
per annum
Unrestricted
Grants:
Pharma
Dr Anil Mehta has no conflicts or disclosures to declare:
Blue areas:ECFS
Registry
EuroCareCFEuroCareCF
Registries Used To COMBAT Disparities in Health Outcomes
• Origins of the common cystic fibrosis (CF) gene mutant
– KEY FACT 1: this only happened once, in 1 baby and yet today we have 1:60 carriers in Europe
• Patterns if you inherit 2 mutants i.e. the CF Population
– KEY FACT 2: Lack of universal screening at birth,
– Cost to Europe in lost Parental Productivity
• Use of Registry to influence policy
– Die with dignity in full publicity, not silently
– Gather the best evidence, through registries (Lancet)
This baby was a super-survivor against common childhood killers
• Common Mutation in the cystic fibrosis (CF) gene
– KEY FACT 1: Only once in human history was a baby was born with 3 adjacent DNA base pairs missing in 1 gene on 1 chromosome 7
• Patterns of ‘double carriers’ i.e. the CF Population
– KEY FACT 2: Lack of universal screening at birth,
– Cost to Europe in lost Parental Productivity
• How can patients fight back against injustice?
– Die with dignity in full publicity, not silently
– Gather the best evidence, through registries (Lancet)
Deaths:SmallpoxDiarrhoea Pneumonia TBMalaria
CE-2K
DF508, Phe508del
2014BCE
-10K
3 base pairs lost on chromosome 7 in a single gene cftr
-50K
25%
75% (3 in 4 children died before 6 years of agei.e. no gene transmission)
25% populate the next 100%With an excess number of Phe508del
Protection?
ATC ATC TTT GGT GT T
ATC ATT GGT GT TIle Ile Gly Val
Ile Ile Phe Gly Val506 507 508 509 510
506 507 509 510
AMAZINGLY TODAY: 1 in 60 Europeans carry this protective chromosome
Fibrogenicum - carrierBaby FibrogenicusBaby Fibrogenica
Over generations, the CF F508del-CFTR gene carriers became enriched
FROM 1 INFANTCHILD
1:60DF508DF508
HealthyEU-carrierCitizensToday
Fibrogenicum’sOffspring
Out surviveFellow babies
All offspring inheriting two copies when carriers mated died for 5000 + years
CFTR Picture from DN Sheppard (Bristol) En passant
F508del
F508del
F508del
EUROPEAN INCIDENCE ~1:4000
Finland 25,000
Turkey <10,000
Sweden 7,300
Poland 6,000
Northern Ireland 5,350
Russian Federation 4,900
Denmark 4,700
Estonia 4,500
Norway 4,500
Netherlands 3,650
Greece 3,500
Spain 3,500
Germany 3,300
Czech Republic 2,833
United Kingdom 2,600
Italy 2,438
France 2,350
Switzerland 2,000
Scotland 1,984
Ireland 1,800
USA 3,500
WHOEvery ~4000th baby born pays an early death price
Patients in 5-year Age Groups
12
1617
16
14
10
6
9
0
2
4
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0-5y 5-10y 10-15y 15-20y 20-25y 25-30y 30-35y 35+y
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More than 40,000 EU citizens
Surely, a debt is owed by the member states :
From the population entry of a protective gene on chromosome 7 that has kept
so many Europeans healthy for thousands of years
Patients in 5-year Age Groups
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5
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0-5y 5-10y 10-15y 15-20y 20-25y 25-30y 30-35y 35+y
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Patients in 5-year Age Groups
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Patients in 5-year Age Groups
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30
35
0-5y 5-10y 10-15y 15-20y 20-25y 25-30y 30-35y 35+y
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Patients in 5-year Age Groups
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FP6: EurocareCF brought this data to the EUThrough a simple quantitative Registry
McCormick et al Lancet 2010
Country A
Country B Country D
Country C
Patients in 5-year Age Groups
12
1617
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14
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6
9
0
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4
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Interpreting the CF profile of Europe
• Common Mutation in the cystic fibrosis (CF) gene
– KEY FACT 1: this only happened once, in 1 baby and yet today we have 1:60 carriers in Europe
• Divergent patterns of these ‘doubly inherited mutations’
• KEY FACT 2: Lack of universal screening at birth, – Does it matter if a child with CF turns up already damaged?
Registries again give us an answer
• How can patients fight back against injustice?
– Die with dignity in full publicity, not silently
– Gather the best evidence, through registries (Lancet)
Dijk FN, et al. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Archives of disease in childhood. 2011;96(12):1118-23.
No screening
Newborn screening, yes
75%
alive
50%
Alive
25 years
later
Australian experience
Patients in 5-year Age Groups
12
1617
16
14
10
6
9
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0-5y 5-10y 10-15y 15-20y 20-25y 25-30y 30-35y 35+y
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If 1500 children were kidnapped: Headline News
0-5 yr 5-10 yr 10-15 yr 15-20 yr 20-25 yr 25-30 yr 30-35 yr >35 yr Total
3549 4676 4922 4795 3945 2768 1854 2584 29093
12% Pre-school
%
~1500 Missing pre-schooli.e. no newborn screen
Firstschool
Teenagechildren
~3550
Does it cost less
not to screen
In years 1-7?
No screening
Newborn screening, yes
75%
alive
50%
Alive
25 years
later
$500
Per-Patient annual cost in US Dollars
$500-$5000If unscreened
50:50 split In costs
>$25,000 p.a.
Sims et al
Lancet2007CoverFeature
screened100 b
ab
ies
Per-Patient annual cost in US Dollars
Registries Used To Measure Disparities in Health Outcomes
• Origins of the common cystic fibrosis (CF) gene mutant
– KEY FACT 1: this only happened once, in 1 baby and yet today we have 1:60 carriers in Europe
• Patterns of ‘double carriers’ i.e. the CF Population
– KEY FACT 2: Lack of universal screening at birth,
– Cost to Europe in lost Parental Productivity
• Can we use this Registry Data to influence policy?
– How can our experience help you in your goals?
How did we get the data? The old way
NO EPR patients attended for full day assessment -‘Annual Review’
Results handwritten, summary dictated by Consultant and then typed by secretaries….delay
Clinic letters and discharge summaries dictated and typed Standard data forms to get the data into analytic audit Excel spread sheet in 2000-2005
Registry/Audit1995-2005
Electronic patient record system Clinical audit programme
Improved standards of patient care and outcomesIncreased service efficiency
In 2007 - EPR system introduced in Adult CF Unit: Dr Daniel Peckham’s new way
INTEGRATION
Daniel Peckham’s key foundations –EPR AUDIT
• Code & structure
• Defining terms in Snomed CT
• Talking same language
• Linking EPR systems
• Quality, Safety, Better Care
MDT office – shared space with full access to EMIS®
The Adult ward – all theTeam use EMIS to run the ward
Clinic rooms – Seacroft and St James’s
Seminar Room – all WRs done using EMIS®
Daniel has entered the lion’s den : his Future???• Leeds CF services moving from PCS to EMIS WEB 5/2014.
• Testing web for General respiratory medicine / Bronchiectasis / TB / Asthma / PCD: Multi disease platform
• TODAY AS I SPEAK: Trial in Manchester and Trial in Sheffield
• Data retrieval – and data transfer now much easier.
• 35 patients
• 6 Rheumatoid
• 29 CF related Arthritis
• Sex distribution
• Age distribution
• Any genotype or phenotype data available for export.
Qu– how many of your CF patients have arthritis and what is the pattern of inflammation?Answer – 5 min
AT AN EU Level: Web-based software
Open source
Flexible add-on modules
Easy interface
EU level SOLVED: data entry,
transmission, error reporting and data extraction
European Data Protection compliant
Remote Robust Transparent management standards
publically available
FP6: value for money
Whatever disease you work on
ECFS working with the SME Open App
2006-2014
2014-2019
The vision 2014-2019 needs 3 steps1
23
Data-Ethics (New Regulations)De-identification
Software
Research-ready
Data SAFE
Re-assembly
The future
Is here
In summary by building such Data SafesGood Data : Policy : EU Health
• An ancient debt is owed by healthy European Taxpayers
• That debt can be affordably repaid
– Screen at birth, give every 4000th baby a chance
– Make best practice the normal practice, trans-nationally
– Registry based evidence base published in Lancet (2007-10)
– New EPR software now being rolled out
– Integrate audit with care with EPR but code carefully
• This is transformational science from DNA/genetics to
• Politics and health care:
EuroCareCFEuroCareCF
We have assembled a team who know how to anonymise the data
Two SMEs who know data linkage and project management
ECFS as a support network (through screening and genetics)
H2020, application submitted..pending
See Findacure.org and www.ecfs.eu
SKILL MIX TO BUILD CF-SAFE IS READY
CF-Safe as a virtual tool i.e. with Cloud-safe Analytics
No history of pseudomonas infectionPseudomonas screen negativeIntermittent pseudomonas infectionChronic pseudomonas infectionPseudomonas aeruginosa - mucoid strainPseudomonas aeruginosa - non mucoid strainNo history of burkholderia cepacia complex infectionIntermittent burkholderia cepacia complex infectionChronic burkholderia cepacia complex infectionBurkholderia cepacia complex screen negativeBurkholderia gladioliBurkholderia cepacia complex statusBurkholderia cepacia (Burkholderia cepaciacomplex genomovar I)
We now have hundreds of SNOMED-CT codes
From Peckham et al 2014 J Cyst Fibrosis
ALBANIA ESTONIA ICELAND LITHUANIA
LUXEMBOURG MACEDONIA SLOVENIA (SCOTLAND)
BULGARIA DENMARK HUNGARY IRELAND NORWAY
SERBIA CZECH R SLOVAKIA SWEDEN SWITZERLAND
GREECE NETHERLANDS PORTUGAL
FRANCE GERMANY ENGLAND ITALY POLAND ROMANIA
SPAIN UKRAINE
We want to capture all screen positive Cf children
EU Commission Commentary
MEHTA et al J CF, 2010 FREE FOR DOWNLOAD
30%
How will we know that the CF care money is well spent:
Turn patients into tax payers
Males Females
Born in 1960-79
1989
Eur Respir J. 2007 29:522-6 …….Data from the UK
100 children diagnosed with CF,Very few die in the UK, France etc over first decade
i.e. less than 5% by 15 years
100
Children
Potential Tax
payers
Measuring success
Go to stored blood spot cardsLiterature on incidence
Neonatal screening for cystic fibrosis is beneficial even in the context of modern treatment:
2 months of age is latest to start therapy
CDC Atlanta, J Pediatrics:
Volume 147, Issue 3, Supplement ,
Pages S42-S46, September 2005
CDC Atlanta/WHO/Australia
Many papers: Michael and Philip Farrell
UNSCREENEDClinical Diagnosis% FEV1/FVC
Screened DiagnosisDrug number
intensity
You need fewer drugs for the same outcomeIf you screen at birth..
$4500
Sims et al The Lancet, Volume 369, Issue 9568, Pages 1187 - 1195, 2007 :
IF WE USE LUNG DISEASE AS AN OUTCOME
Can we quantify the drug costs: Lancet 2007?
Admissions to hospital (Wilcken & Chalmers Lancet 1985)
COHORT MEAN HOSPITAL DAYS
UNSCREENED, no MI, born 1978-1979 n=24 27.5 (range 0-112)
UNSCREENED, no MI, born 1979-1981 n=24 27.0 (range 0-240)
SCREENED, no MI, born 1981-1982 n= 17 3.4 (range 0-20)
SCREENED, no MI, born 1982-1983 n=17 4.4 (range 0-31)
MECONIUM ILEUS, Screened and unscreened, born 1978 to 1983 n=16
16
No admissions: Unscreened 15/48 (31%) screened 24/34 (71%) p <0.0005
Admission > 21d: Unscreened 20/48 (42%) screened 1/34 (3%) p< 0.0005
Slide from Bridget Wilcken, Australia
All Europe patients
ALLCF
44%Common
Type
98% can be diagnosed by 15 yearsPROVIDED healthcare is good
2% turn up as adults
Patients in 5-year Age Groups
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If any EU health care system is able to diagnose CF(and you don’t screen) and if that system can maintain their health
0-5 yr 5-10 yr 10-15 yr 15-20 yr 20-25 yr 25-30 yr 30-35 yr >35 yr Total
3549 4676 4922 4795 3945 2768 1854 2584 29093
%
Firstschool
Teenagechildren
~3550
FIVE THOUSAND CF Patients for each middle 5yr Bin
+%0%
-%
-%
Age in years
0-<1
010
-<20
20-<
3030
-<40
40-<
5050
-<60
60-<
7070
-<80
% c
hang
e in
CF
popu
latio
n si
ze fr
om p
revi
ous
deca
de
-100-90-80-70-60-50-40-30-20-10
0102030
Rising population
Falling population
Podcast Lancet 2010: March 20Evidence for any Government
To see and challenge
Age in years
0-<1
010
-<20
20-<
3030
-<40
40-<
5050
-<60
60-<
7070
-<80
% c
hang
e in
Fde
l508
/Fde
l508
C
F po
pula
tion
size
from
pre
viou
s de
cade
-100-90-80-70-60-50-40-30-20-10
0102030All CF F508del / F508del
Child-CF type
Western Europe,Established
Member statesNewEU
MembersIn 2004
IF WE HAD SCREENING AT BIRTH, they could get careAt their nearest CF centre, or cross-border care if not available
Lancet. 2010 Mar 20;1007-13.
doi: 10.1016/S0140-6736(09)62161-9
