Transcript Presentation Title - HRB - Grant Holders Conference

HRB Grant Holders Conference
Limerick
February 26-27, 2015
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Consortium Background
All-Ireland multi-centre consortium focused on
research into maternal and child health
Health Research Board (HRB) funded (€4.9 million)
Additional external funding (€2.8 million)
- Friends of the Rotunda
- National Children’s Research Centre
- Children’s University Hospital Research Fund
- Science Foundation Ireland
- Wellcome Trust
Links seven maternity hospitals and associated
academic centers across the island
Network Partners
Maternal Fetal Medicine Support
Universal National Support
COOMBE
Bridgette Byrne
Sean Daly
Mairead Kennelly
Caoimhe Lynch
Aisling Martin
Carmen Regan
CORK
Richard Greene
John Higgins
Dan McKenna
Keelin O’Donoghue
Noirin Russell
NMH
Stephen Carroll
Mary Higgins
Shane Higgins
Rhona Mahony
Fionnuala McAuliffe
Peter McParland
ROTUNDA
Fionnuala Breathnach
Sharon Cooley
Jennifer Donnelly
Karen Flood
Fergal Malone
BELFAST
Carolyn Bailie
Samina Dornan
Aly Hunter
John Manderson
Stephen Ong
GALWAY
Geraldine Gaffney
John Morrison
LIMERICK
Amanda Cotter
John Slevin
WEXFORD
Liz Dunne
Additional Multidisciplinary Support
NEONATOLOGY
David Corcoran
Adrienne Foran
John Kelleher
Pamela O’Connor
Colm O’Donnell
David Sweet
CARDIOLOGY
Orla Franklin
Dermot Kenny
PHARMACY
Brian Cleary
RADIOGRAPHY
Fiona Cody
Edel Varden
MASTERS / CD’s
Sam Coulter Smith
Rhona Mahony
Sharon Sheehan
All clinical directors
RADIOLOGY
James Meaney
HSE
Michael Turner
EPIDEMIOLOGY
Patrick Dicker
Richard Tremblay
INDUSTRY
Colin Paul
Gerald Seifriedsberger
MIDWIFERY
Fiona Alderdice
Mary Brosnan
Emma Doolin
Phyl Gargan
Cecilia Mulcahy
Hilda O’Keeffe
Margaret Philbin
Ann Phillips
INTERNATIONAL
Zarko Alfirevic
Ted Barker
Mary D’Alton
Tim Lyons
Jane Norman
Michael Paidas
Andrew Shennan
Ian Young
Personnel Structure
Chairman – Prof Fergal Malone
Programme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker
Personnel Structure
Chairman – Prof Fergal Malone
Programme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker
PI – Prof F McAuliffe
RS- Cecelia Mulcahy
PI – Prof J Morrison
RS- Edel Varden
PI – Prof F Breathnach
RS- Fiona Cody
PI – Prof J Higgins
RS- Ann Phillips
PI – Prof S Daly
RS- Emma Doolin
PI – Dr G. Burke /
Prof A Cotter
RS- K Irfah-Ismail
PI – Dr Aly Hunter/
Dr Samina Dornan
RS- Phyl Gargan
Management Structure
Scientific
Advisory
Board
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Steering Committee comprised of Chairman, Site
PIs , Programme Manager,
Biostatistician, Sonographer &
Patient representatives
RCSI Research
Institute
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Health
Research
Board
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CLINICAL SITES
Rotunda Hospital
Coombe Women and Infants
University Hospital
National Maternity Hospital
University College Hospital,
Galway
Royal Jubilee Maternity Hospital,
Belfast
Mid-Western Regional Maternity
Hospital, Limerick
Cork University Maternity
Hospital
Education
& Training
Protocol
Publication
Finance
Sub-Committees
Research Infrastructure
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Unique, world-class research infrastructure comprising :
– state-of-the-art imaging equipment
• GE Voluson Ultrasound Equipment & Viewpoint Software
– dedicated research and management personnel
• Research Sonographers, Programme Manager, Biostatistician
– central management and governance structure
• Steering Committee, Scientific Advisory Board, RCSI Research Institute
– access to associated support services
• Pathology, Epidemiology, Range of specialist cross-disciplinary clinical expertise
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Access to large patient populations (55,000+ births pa.):
– uniquely positioned to carry-out ground-breaking
clinical research.
Network Aims
Perinatal Ireland was established with the mission of improving
the standard of healthcare for women and children in Ireland.
Key goals and objectives
• to establish a centre of excellence in perinatal medicine research, performing
world-class clinical research
• to build a national dedicated research capacity to conduct high-quality patientoriented clinical research
• to translate research findings into clinical practice for the benefit of women and
children’s health
• to develop collaborative, cross-disciplinary programmes to generate national
research networks
• to develop human capital through high-quality education and training programmes
Research to date
 ESPRiT – National Twin Study
– Two year Programme to Jan 2010
– Recruited over 1000 twin pregnancies
– Multiple high profile publications
– Multiple oral presentations at Society for Maternal Fetal Medicine Annual Clinical
Meeting
– Long term paediatric follow-up ongoing
– Long term epigenetic studies ongoing
– Published new national guidelines on the management of twin pregnancies
Research Studies
PORTO - investigation of multi-vessel Doppler in the management
of growth restricted fetuses:
• Two year programme to June 2012
• Recruited over 1200 patients
PORTO 1:
The Optimal Definition of Intrauterine Growth Restriction Based
on Perinatal Morbidity and Mortality
J. Unterscheider on behalf of Perinatal Ireland
Oral Presentations at SMFM, San Francisco, Feb 2013
PORTO 1:
Methods
• 1,200 consecutive singleton pregnancies 24 0/7 – 36 6/7 wks
• EFW < 10th centile
• Followed with twice weekly ultrasound / advanced Doppler:
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Biometry / amniotic fluid
Uterine artery
Umbilical artery
Ductus venosus
Middle cerebral artery
Aortic isthmus
Myocardial performance index
PORTO 1:
Methods
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Detailed obstetric and pediatric outcome
Neonatal US and MR Imaging
2 year Bayley’s assessments
Adverse outcome:
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Perinatal mortality
NICU admission
IVH / PVL
HIE
NEC
BPD
Sepsis
PORTO 1:
Methods
• Various definitions of significant IUGR:
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EFW < 10th, < 5th, < 3rd centiles
AC < 10th, <5th, < 3rd centiles
All with or without oligohydramnios
All with or without abnormal umbilical artery Doppler (AEDF / PI >95%)
PORTO 1:
Results
• Perinatal Mortality
• Composite Adverse Perinatal Outcome
• NICU Admission
1.4% (17)
6.2% (74)
31% (372)
PORTO 1: Results
Predictor
n
Adverse outcome (n=60)
Normal outcome (n=1058)
P-value
EFW<3rd
828
53 (88.3%)
775 (73.3%)
0.0095
EFW<5th
1049
57 (95.0%)
992 (93.8%)
0.6982
EFW<10th
1118
60 (100%)
1058 (100%)
N/A
AC<3rd
911
54 (90.0%)
857 (81.0%)
0.0809
AC<5th
1000
55 (91.7%)
945 (89.3%)
0.5649
AC<10th
1082
58 (96.7%)
1024 (96.8%)
0.9592
EFW<3rd + oligo
128
14 (23.3%)
114 (10.8%)
0.0030
EFW<5th + oligo
190
14 (23.3%)
176 (16.6%)
0.1790
EFW<10th + oligo
232
16 (26.7%)
216 (20.4%)
0.2454
EFW<3rd + abnormal UA
251
42 (70.0%)
209 (19.8%)
<0.0001*
EFW<5th + abnormal UA
346
45 (75.0%)
301 (28.4%)
<0.0001*
EFW<10th + abnormal UA
413
47 (78.3%)
366 (34.6%)
<0.0001*
PORTO 1:
Conclusions:
• EFW or AC < 10th or 5th centiles should no longer be used to
define pregnancies at high risk adverse outcome
• EFW < 3rd centile is reasonable cut-off to define high risk
group
• Abnormal UA Doppler is strongest predictor of adverse
outcome whenever EFW < 10th centile
• These data will allow more focussed use of obstetric
resources whenever EFW < 10th centile
PORTO 2:
Sequential Doppler Changes in IUGR: Is There a Benefit of
Advanced Multi-Vessel Doppler Assessment?
J. Unterscheider on behalf of Perinatal Ireland
Oral Presentation at SMFM, San Francisco, Feb 2013
PORTO 2: Results
PORTO 2:
Results
UA
MCA
DV
AoI
MPI
GA at first
abnormal Doppler
32 6/7
32 5/7
32 4/7
30 6/7
33 1/7
Median time to
delivery
23 d
21 d
17 d
21 d
29 d
GA at delivery
37 3/7
37 2/7
34 5/7
38 1/7
38 4/7
PORTO 2:
Conclusions:
• Umbilical artery and MCA Doppler are most predictable in
demonstrating progressive temporal changes for IUGR
• Ductus venosus and cardiac indices demonstrated no added
benefit in surveillance for IUGR
• Surveillance for IUGR should be simplified and should rely
primarily on finding of AEDF or REDF in umbilical artery
• New HSE National Guideline published
Current Studies
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GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC),
measured using ultrasound in the late third trimester, and other markers as predictive tools for
labour dystocia and intrapartum caesarean section.
– Recruitment target : 2500 (achieved Dec 2014)
– Study duration : 36 months (outcomes ongoing)
Current Studies
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GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC),
measured using ultrasound in the late third trimester, and other markers as predictive tools for
labour dystocia and intrapartum caesarean section.
– Recruitment target : 2500 (achieved Dec 2014)
– Study duration : 36 months (outcomes ongoing)
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AFFIRM – Fetal Movement study - Can promoting awareness of fetal movements and focussing
interventions reduce fetal mortality - a stepped wedge cluster randomised trial?
– Hospital education and intervention programme
– Study duration : 24 months
Current Studies
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GENESIS – Prospective observational study to assess the use of fetal head circumference (FHC),
measured using ultrasound in the late third trimester, and other markers as predictive tools for
labour dystocia and intrapartum caesarean section.
– Recruitment target : 2500 (achieved Dec 2014)
– Study duration : 36 months (outcomes ongoing)
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AFFIRM – Fetal Movement study - Can promoting awareness of fetal movements and focussing
interventions reduce fetal mortality - a stepped wedge cluster randomised trial?
– Hospital education and intervention programme
– Study duration : 24 months
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TEST – Randomised trial of aspirin therapy and early screening tests for pre-eclampsia and fetal
growth restriction, during pregnancy in low-risk first-time mothers
– Recruitment target : 5,700
– Pilot study target: 500 (250 recruited to date)
Future Direction?
HRB Ireland Perinatal Clinical Trial Network: Mission
• To improve health outcomes
for women and children,
both in Ireland and globally
HRB Ireland Perinatal Clinical Trial Network:
• Bringing together two highly successful,
existing, clinical research networks in the
perinatal arena
Overwhelming need
• More than 1 in 10 babies are
born preterm
• Over 1 million children die each
year due to complications of
preterm birth
• Many survivors face a lifetime of
disability, including learning
disabilities and visual and hearing
problems
Economic need
• Perinatal disease accounts
for 10% of the global health
burden1
• R&D investment in perinatal
health remains small and
non-strategic
• The number of registered
pipeline drugs is only 1-5%
that for other major disease
areas
1. Fisk, N.M. and R. Atun, Market failure and the poverty of new drugs
in maternal health. PLoS Med, 2008. 5(1): p. e22.
HRB Ireland Perinatal Clinical Trial Network: Vision
HRB Ireland Perinatal Clinical Trial Network:
International Collaborations
HRB Ireland Perinatal Clinical Trial Network: Expertise
Biochemistry
Masters &
Clinical Directors
Cardiology
Maternal Fetal
Medicine
Pathology
Neonatal
Physiology
Neonatology
Epidemiology
Endocrinology
Trials Methodology
Developmental
Psychology
Haematology
General
Practice
Directors Nursing
& Midwifery
HRB Ireland Perinatal Clinical Trial Network:
Governance Structure
CLINICAL SITES
Health
Research
Board
Clinical
Research
Facilities
External
Scientific
Advisory Board
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Executive
Management
Committee
Rotunda Hospital
Coombe Women’s Hospital
National Maternity Hospital
University Hospital, Galway
Royal Maternity, Belfast
MW Regional Hospital, Limerick
Cork University Maternity
Hospital
Industrial Liaison
Business
Development
Education
& Training
Protocol
Publication
Finance
Management Sub-Committees
HRB Ireland Perinatal Clinical Trial Network:
Portfolio of Trials - New
• Implement two Definitive Intervention studies
Strider DI
Parrot DI
• Pilot & Feasibility Work
TEST
MINT
IRELAND
• Launch network programme of bespoke, clinical assessment
of longer term paediatric outcomes
Paediatric Follow up
• Launch research programme in Clinical Trials Methodology
Core Outcome Set