hrb grant holders conference limerick february 26-27, 2015
TRANSCRIPT
HRB Grant Holders Conference
LimerickFebruary 26-27, 2015
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 SupportUniversal National Support
ROTUNDAFionnuala BreathnachSharon CooleyJennifer DonnellyKaren FloodFergal Malone
COOMBEBridgette ByrneSean DalyMairead KennellyCaoimhe LynchAisling MartinCarmen Regan
NMHStephen CarrollMary HigginsShane HigginsRhona MahonyFionnuala McAuliffePeter McParland
CORKRichard GreeneJohn HigginsDan McKennaKeelin O’DonoghueNoirin Russell
GALWAYGeraldine GaffneyJohn Morrison
LIMERICKAmanda CotterJohn Slevin
BELFASTCarolyn BailieSamina DornanAly HunterJohn MandersonStephen Ong
WEXFORDLiz Dunne
Additional Multidisciplinary Support
RADIOLOGYJames Meaney
NEONATOLOGYDavid CorcoranAdrienne ForanJohn KelleherPamela O’ConnorColm O’DonnellDavid Sweet
EPIDEMIOLOGYPatrick DickerRichard Tremblay
CARDIOLOGYOrla FranklinDermot Kenny
MIDWIFERYFiona AlderdiceMary BrosnanEmma DoolinPhyl GarganCecilia MulcahyHilda O’KeeffeMargaret PhilbinAnn Phillips
MASTERS / CD’sSam Coulter SmithRhona MahonySharon SheehanAll clinical directors
PHARMACYBrian Cleary INTERNATIONAL
Zarko AlfirevicTed BarkerMary D’AltonTim LyonsJane NormanMichael PaidasAndrew ShennanIan Young
RADIOGRAPHYFiona CodyEdel Varden
INDUSTRYColin PaulGerald Seifriedsberger
HSEMichael Turner
Personnel StructureChairman – Prof Fergal Malone
Programme Manager – Dr Liz TullyBiostatistician – Dr Pat Dicker
Chairman – Prof Fergal MaloneProgramme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker
Personnel StructureChairman – Prof Fergal Malone
Programme Manager – Dr Liz TullyBiostatistician – Dr Pat Dicker
Chairman – Prof Fergal MaloneProgramme Manager – Dr Liz Tully
Biostatistician – Dr Pat Dicker
PI – Prof F McAuliffeRS- Cecelia MulcahyPI – Prof F McAuliffeRS- Cecelia Mulcahy
PI – Prof F BreathnachRS- Fiona Cody
PI – Prof F BreathnachRS- Fiona Cody
PI – Prof S DalyRS- Emma DoolinPI – Prof S Daly
RS- Emma DoolinPI – Prof J Morrison
RS- Edel VardenPI – Prof J Morrison
RS- Edel Varden
PI – Prof J HigginsRS- Ann Phillips
PI – Prof J HigginsRS- Ann Phillips
PI – Dr G. Burke / Prof A Cotter
RS- K Irfah-Ismail
PI – Dr G. Burke / Prof A Cotter
RS- K Irfah-Ismail
PI – Dr Aly Hunter/Dr Samina Dornan
RS- Phyl Gargan
PI – Dr Aly Hunter/Dr Samina Dornan
RS- Phyl Gargan
Management Structure Steering Committee -
comprised of Chairman, Site PIs , Programme Manager,
Biostatistician, Sonographer & Patient representatives
Steering Committee - comprised of Chairman, Site
PIs , Programme Manager, Biostatistician, Sonographer &
Patient representatives
Scientific Advisory
Board
Scientific Advisory
Board
RCSI Research Institute
RCSI Research Institute
Health Research
Board
Health Research
Board
Education & TrainingEducation & Training
FinanceFinancePublicationPublication
ProtocolProtocol
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
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
Sub-Committees
Research Infrastructure • 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
• Access to large patient populations (55,000+ births pa.):– uniquely positioned to carry-out ground-breaking
clinical research.
Network AimsPerinatal 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 patient-oriented 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 StudiesPORTO - 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 MortalityJ. Unterscheider on behalf of Perinatal IrelandOral 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:
– Biometry / amniotic fluid– Uterine artery– Umbilical artery– Ductus venosus– Middle cerebral artery– Aortic isthmus– Myocardial performance index
PORTO 1:Methods
•Detailed obstetric and pediatric outcome•Neonatal US and MR Imaging•2 year Bayley’s assessments•Adverse outcome:
– Perinatal mortality– NICU admission– IVH / PVL– HIE– NEC– BPD– Sepsis
PORTO 1:Methods
•Various definitions of significant IUGR:– 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 1.4% (17)•Composite Adverse Perinatal Outcome 6.2% (74)•NICU Admission 31% (372)
PORTO 1: ResultsPredictor 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 IrelandOral 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• 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• 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)
• 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• 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)
• 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
• 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 outcomesfor 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
Trials MethodologyTrials Methodology
Maternal Fetal Medicine
Maternal Fetal Medicine
NeonatologyNeonatology
General PracticeGeneral Practice
EpidemiologyEpidemiology
Developmental Psychology
Developmental Psychology
PathologyPathology
BiochemistryBiochemistryCardiologyCardiology
HaematologyHaematology
EndocrinologyEndocrinology
Neonatal PhysiologyNeonatal
Physiology
Masters & Clinical Directors
Masters & Clinical Directors
Directors Nursing & Midwifery
Directors Nursing & Midwifery
HRB Ireland Perinatal Clinical Trial Network: Expertise
HRB Ireland Perinatal Clinical Trial Network: Governance Structure
Executive Management
Committee
Executive Management
Committee
External Scientific
Advisory Board
External Scientific
Advisory Board
Clinical Research Facilities
Clinical Research Facilities
Health Research
Board
Health Research
Board
CLINICAL SITES
•Rotunda Hospital•Coombe Women’s Hospital•National Maternity Hospital•University Hospital, Galway•Royal Maternity, Belfast•MW Regional Hospital, Limerick•Cork University Maternity Hospital
CLINICAL SITES
•Rotunda Hospital•Coombe Women’s Hospital•National Maternity Hospital•University Hospital, Galway•Royal Maternity, Belfast•MW Regional Hospital, Limerick•Cork University Maternity Hospital
Management Sub-Committees
Education & TrainingEducation & Training
FinanceFinancePublicationPublicationProtocolProtocol
Industrial Liaison Business
Development
Industrial Liaison Business
Development
HRB Ireland Perinatal Clinical Trial Network: Portfolio of Trials - New
• Implement two Definitive Intervention studies Parrot DIParrot DI Strider DIStrider DI
TESTTEST MINTMINT IRELANDIRELAND
• Pilot & Feasibility Work
• Launch network programme of bespoke, clinical assessment of longer term paediatric outcomes
Paediatric Follow upPaediatric Follow up
Core Outcome SetCore Outcome Set
• Launch research programme in Clinical Trials Methodology