INFANT specialises in Biomarker discovery and validation in neonates, in infant and maternal nutrition research and CTIMP studies in neonates for hypotension and seizures.
An area of focus is Neonatal Brain Research – using enhanced real time multi modal physiological monitoring at the cot-side. We develop algorithms that can reliably and remotely monitor complex physiological data.
Areas of focus at INFANT are:
Hypotension in extremely preterm infants; Neonatal Seizures; Perinatal asphyxia; Hypoxic-Ischemic Encephalopathy; Neonatal Stroke; Pre-eclampsia and conditions of late pregnancy; Short and long term neurodevelopmental outcomes; Nutritional studies; Cardio-respiratory conditional of the neonate
NEURO-DEVELOPMENTAL FOLLOW UP
Neurodevelopmental Follow up is an important measure of outcome in high risk infants not only from a clinical viewpoint but also in regards to the true assessment of outcomes of clinical and societal interest in neonatal clinical research. INFANT has always prioritised the follow-up not only of our high risk cohorts but our longitudinal healthy cohorts and health research studies. Follow-up of healthy cohorts gives us unique national control data against which our high risk cohorts can be accurately assessed.
For example the BASELINE cohort has been used as matched controls for many of our brain injury studies and is one of the largest healthy cohorts studies in Europe. Over 1600 first time mothers took in part in the SCreening fOr Pregnancy Endpoints (SCOPE) study and the majority of mothers and their INFANT have enrolled in the on-going Cork BASELINE Birth study, Ireland’s first and only birth cohort. This detailed maternal study has allowed us access to important information about this large group of babies from early fetal life. We have information about their mother’s diet, lifestyle and health from the time that they are 15 weeks pregnant. Follow up of the BASELINE children has taken place in the Health Research Board- Clinical Research Facility- Cork Discovery Centre in Cork University Hospital. Children have be seen at 2, 6, 12, 24 months and 5 years.
The Neonatal Brain Injury Group (NBRG) at Cork University Maternity Hospital was established in 2003 to investigate brain injury in newborn babies. Professor Boylan led a multidisciplinary team of physicians, nurses, engineers and scientists seeking to improve the long term health outcomes of newborn babies through early and accurate detection of neurological problems. Several studies emerged from this collaboration and a neurodevelopmental outcome strategy was incorporated as an important outcome measure.
In particular Hypoxic Ischaemic Encephalopathy (HIE) was studied by Dr Deirdre Murray to ultimately find a biomarker that would identify the 20% of neonates who require intervention after perinatal asphyxia. From the BiHIVE Study a cohort of approximately 500 cases and 300 controls have been collected and vital neurodevelopmental testing has been undertaken.
In 2013 the NBRG became part of the new formed Science Foundation Ireland INFANT Centre based in Cork University Maternity Hospital creating Irelands first perinatal research centre. The focus of INFANT is on developing solutions to address the unmet worldwide clinical need for effective screening tests for the most common complications of pregnancy and the most significant problems for newborn babies.
In 2016 INFANT took ownership of a dedicated suite of assessment rooms including a sleep study room, Bayley’s assessment room and observation room. This infrastructure will be further expanded in late 2016/early 2017 with the provision of an Early Life Lab, with additional assessment rooms and facilities, in the new Paediatric Build in Cork University Hospital. INFANT has expertise in the completion and evaluation of the many standardised Neurodevelopmental assessments including:
– Ages and Stages Questionnaire (ASQ-3)
– Child Behaviour Checklist (CBCL: Achenbach & Rescoria, 2000)
– Social-Emotional and Adaptive Behaviour Questionnaire from BSID-III
– Bayley Scales of Infant Development III (BSID-III)
– Kaufman Brief IQ test
– Revised Griffiths Scales of Mental Development
– NEPSY® – Second Edition
– Wechsler Preschool and Primary Scale of Intelligence™ – Third Edition (WPPSI™ – III)
– Behavior Rating Inventory of Executive Function®–Preschool Version (BRIEF®-P)
– Executive function imitation working memory task
– Greenspan Social-Emotional Growth Chart
– WPPSI working memory scale
– MacArthur-Bates Communicative Development Inventories (CDI)
– Baby Screen APP- a tablet based psychological assessment tool, which measures cognitive ability in an engaging and interactive way at 18-30 months.
In the years since its inception; the INFANT’s biobank has been managed to become the foundation for high quality annotated biological samples for biomedical research within INFANT. The value of this lies not only in the samples themselves but with the clinical metadata associated with each specimen. The secure use of customised, project specific databases by specialised provider MedSciNet permits biobanking across multi-centred sites, nationally and internationally.
The 1 million ethically collected samples held in INFANT’s Biobank are stored in a resource that aims to meet and exceed national and international biobanking guidelines by OECD, MMI and ISBER. This is enhanced by INFANT’s active participation in international standards development in the area of biobanking and bioresources. The Biobank currently accommodates a unique collection of biological specimen types and annotated data stored according to projects including aliquots of serum, EDTA plasma, heparin plasma, citrate plasma, urine, skin, buffy coats and whole blood, tempus tubes, cervical swabs and umbilical cord tissue. Saliva and hair are also stored for selected projects.
INFANT’s success in 2016 in securing funding for creation of an offsite biostorage facility will enable creation of an additional secure, restricted access facility with backup power supply and an auditable temperature monitoring alarm/alert system to bolster biobanking activities. The two disparate locations will help to relieve current operational risks, including health and safety risks, massively increase capacity, and provide the opportunity for prevention of catastrophic loss in the event of partial biobank disaster in either location for rare collections.
Since 2003, INFANT has collected clinical and physiological data from pregnant women and newborn babies admitted to the Neonatal Intensive Care Unit (NICU) at Cork University Maternity Hospital who have participated in a diverse array of nationally and internationally funded cohort studies and trials. These are large ‘big data’ sets containing multichannel physiological information on neurological, cardiovascular and respiratory function in neonates of all gestational ages. In addition, INFANT stores and manages data from other Maternity Units and NICUs across Europe; particularly from centres collaborating with INFANT on EU funded clinical trials such as HIP and NEMO and from our own Wellcome Trust Funded ANSeR trial.
As a consequence of our international leadership in this area, we have now amassed large quantities of clinical and physiological data from thousands of babies through projects such as NEMO, HIP, ANSeR, BASELINE and BIHIVE.
Clinical data acquired from the parents of critically ill neonates is obtained under challenging circumstances. Whilst all clinical research in INFANT is complaint with good clinical practice guidelines (GCP), data protection and research integrity guidelines and ISO 14155, research involving such ‘vulnerable’ populations is fraught with additional ethical, logistical and regulatory challenges and the legitimacy of patient and parental consent is of paramount importance to INFANT.
INFANT’s Data Management capability is supported by the industry partner MedSciNet. MedSciNet is a Stockholm based company specialising in design and development of web applications and online database systems for clinical trials and studies, quality registries, medical bio-banks, and other solutions within the field of academic medicine. Since the INFANT launch in 2013 a MedSciNet programmer has been based in INFANT. The functionality of the MedSciNet platform is being continuously expanded and improved, thus increasing the effectiveness of the information storage and retrieval for all the future needs. Bug fixes and small upgrades are undertaken as required and this continuous improvement process provides INFANT with exceptional database capabilities. Study Monitoring functionality is an integral part MedSciNet platform and INFANT has dedicated Study monitors who monitor both local study sites and international study sites for many of our multicentre studies. Our BioBank Manager has worked continuously with MedSciNet to develop and implement specialist biobanking functionality in our databases.
The INFANT Discovery Platform Data Hub funded in 2016 allows INFANT to build further capacity for the on-going protection and safe curation of these data and bio-bank repositories and support our Data Management capabilities.
A training program for all personnel who conduct research under the auspice of INFANT is in place and personnel are GCP trained with up to date certificates. This training is delivered in-house by personnel who themselves have been validated and trained as trainers and are certified as such. The training incorporates the relevant regulatory directives/guidelines and legislation in both investigational medicinal products and medical devices. External GCP training and certification can also be provided. Clinical Research Staff are also trained/refreshed at least on a two yearly basis and detailed training logs are maintained.
For Research studies that are monitored by INFANT study specific training is also provided/delivered. This is delivered by an INFANT Study Monitor typically as part of the Site Initiation visit and monitoring visits.
INFANT can provide the skills, expertise and experience to design, conduct, manage and analyse multi-centre, international clinical research involving neonates and children.
QUALITY MANAGEMENT SYSTEM
A Quality Management System (QMS) is in operation in INFANT which helps to ensure the quality of all aspects of a clinical trial/investigation and affirms that the legislative and other applicable requirements are met when conducting clinical research. Quality policies and objectives are outlined in a quality manual and processes and procedures that must be adhered to are described in standard operating procedures. The QMS also includes the process of reviewing adherence to these policies and SOPs, e.g. via quality checks or audits on the documentation that has been generated.
INFANT has dedicated in house monitors who ensure that all ongoing trials are checked and quality controlled on a continuous basis. Each trial will need a different level of control to ensure trial specific risks are managed appropriately. The level and extent of monitoring including source data verification (SDV) that is required is dependent but not limited to, the complexity of the trial design, the patient population, the duration of the trial and generic trial risks e.g. Adverse Event Reporting. At a minimum each trial would have at least two site visits with the consenting process and safety reporting procedure ideally being 100% SDV. All trials are conducted to the “Ethical considerations for clinical trials on medicinal products conducted with the paediatric population”.
Protocols and Clinical Investigation Plans are written according to these guidelines especially the consenting process with regard to obtaining consent in this vulnerable population.
STANDARD OPERATING PROCEDURES
INFANT has SOPs in the following areas:
- Data Management
- Safety Reporting
SOPs include the following:
- Document Control SOP
- Safety Reporting SOP
- Quality Control and Monitoring SOP
- Protocol Generation SOP
- Informed Consent SOP
- Internal & External Audit SOP
- Non Conformance/Deviation and CAPA SOP
- Serious Breach SOP
All SOPs on QC, QA, and Safety Management are publicly available on request.
The core INFANT engineering and clinical competencies are brought together to create clinical decision support systems, converting raw physiological data into meaningful information for diagnosis and prognosis. The strong collaboration between the clinical and engineering teams ensures that the clinicians are fully aware of the available engineering capabilities while the engineers can be assured that they are solving clinically relevant problems.
INFANT utilises the multi-disciplinary expertise of its over 100 staff members and researchers to solve real life problems and identify unmet clinical needs in the perinatal space. Clinicians, nurses, physiologists, physiotherapists and psychologists identify clinical needs, guide development and provide recruitment capability at the second largest Maternity Hospital in Europe. Technological expertise from engineers, system engineers, signal processers, software developers and computer scientists provide ‘hand in glove’ algorithm and software development. Research support in the areas of Bio-Banking, Regulatory, Quality, Monitoring, Biostatistics, Finance and Project Management is provided by experienced INFANT staff. High tech industry collaborations are aligned to individual projects within INFANT, both Science Foundation Ireland funded Targeted/Spoke Projects but also FP7 projects like IMPROvED. Multinational and SME industry partners provide access to cutting edge commercial products that augment INFANTs technical capabilities.