International Neonatal Consortium

Overview

The Problem

More than 96% of neonates receive at least one off-label medication while in the neonatal intensive care unit (NICU). Off-label medications are a normal part of patient care, however their use results in more adverse drug reactions in NICU patients. For medications to be used on-label, or to be indicated, for a specific patient population, they must first be rigorously studied in that population. Unfortunately, designing drug trials in neonates is extremely difficult. There is a persistent unmet need for safe and effective products specifically catering to and studied in neonatal populations.

The Solution

C-Path launched the International Neonatal Consortium (INC) in order to address this unmet need. This global public-private partnership is designed to create a predictable regulatory pathway for evaluating the safety and efficacy of therapies for neonates. INC unites stakeholders from hospitals, research institutions, drug developers, patient advocacy groups, regulatory agencies, and other organizations around the world to generate consensus and develop tools that accelerate medical innovation for neonates.

Through open collaboration in a noncompetitive format, teams share data, knowledge, and expertise, in order to advance medical innovation and regulatory science for this underserved population.

The Impact

INC and its partners have developed guidelines to inform the design of rigorous and efficient clinical trials for potential treatments of neonatal seizures. Neonatal seizures are the most common neurological emergency in neonates, occurring in about 3 in 1,000 term live births, and are associated with significant mortality and neurodevelopmental disability. Trials for this condition are exceedingly difficult and face many challenges, including different diagnostic criteria in different countries, relative rarity in occurrence and the self-limiting nature of many neonatal seizures, which can make them difficult to capture in the setting of a controlled study.

As a result of INC’s work, consensus recommendations were developed and published to address vital aspects of neonatal seizure clinical trials, including considerations for alternative designs, inclusion and exclusion criteria, safety monitoring, appropriate outcome measures, analytical plans and more.

Real-World Data Analytics Platform (RW-DAP)

With the support of FDA’s Office of Medical Policy, INC has initiated an ambitious real-world data integration effort, which will greatly accelerate drug development in neonates. Building on C-Path’s expertise in data integration, analysis, model-informed drug development (MIDD), and regulatory submissions, this effort has already integrated more than 300,000 patient-level data points (Electronic Health Records, registries, clinical trials) and is currently focused on:

• Constructing a quantitative disease progression model for bronchopulmonary dysplasia
• Establishing generalizable neonatal laboratory value reference ranges by age, gender, ethnicity, and other patient-level characteristics

Data integration activities from additional sources are ongoing. RW-DAP is scalable. The MIDD process is disease agnostic. Upcoming use cases will address industry needs by leveraging RW-DAP to establish historical controls for a range of neonatal diseases. The existing data are already capable of supporting other neonatal disease areas.

INC’s work in other focus areas include:

• Real-world data/evidence
• Regenerative therapies
• Neonatal lung injury and circulatory failure
• Retinopathy of prematurity (ROP)
• Neonatal brain Injury
• Prenatal/neonatal infections
• Advancing drugs to prevent preterm labor
• Neonatal Abstinence Syndrome (NAS)/Neonatal Opioid Withdrawal Syndrome (NOWS)
• Hemodynamic adaptation

Additional Resources

Looking for more about INC, like FAQs, information about annual meetings, and general resources? Click here.

Collaborators

Family/Advocacy Organizations

Neonatal Nursing Organizations

Pharmaceutical Industry Members

Government and Regulatory Agencies

• European Medicines Agency (EMA)
• Health Canada
• MHRA (UK) – Medicines and Healthcare products Regulatory Agency
• NICHD (National Institute of Child Health and Human Development)
• PMDA (Japan) – Pharmaceuticals and Medical Devices Agency
• U.S. Food and Drug Administration (FDA)

Academic Institutions

• APHP – South Paris University Hospital
• BC Children’s Hospital
• Boston’s Children Hospital
• Brighton and Sussex Medical School
• The Canadian Neonatal Network/University of Toronto
• Case Western Reserve University School of Medicine
• Children’s Hospital at Montefiore
• Children’s Hospital of Philadelphia
• Children’s Mercy Hospital, Kansas City
• Children’s National Medical Center
• Cincinnati Children’s Hospital Medical Center
• City, University of London
• Columbia University Medical Center
• Cordelier Research Center, French National Institute of Health and Medical Research, INSERM
• Diderot University, Paris
• Duke University
• Emory University
• Erasmus MC-Sophia Children’s Hospital of Netherlands
• Great Ormond Street Hospital
• Harvard University
• Hospital for Sick Children, Toronto, Canada
• Imperial College London
• Indiana University–Purdue University Indianapolis
• Indiana University Health, Riley Hospital for Children
• Jackson Memorial Medical Center, Miami
• Johns Hopkins University
• Karolinska University Hospital
• King’s College, London
• Kurashiki Central Hospital
• Kyorin University
• Mount Sinai Hospital
• Nagano Children’s Hospital
• Nagoya University Hospital
• National Center for Child Health and Development, Tokyo
• Nationwide Children’s Hospital
• Northern Clinical School, The University of Sydney
• NorthShore University HealthSystem
• Oregon Health & Science University
• Osaka City General Hospital
• Osaka University
• Osaka Women’s and Children’s Hospital
• PGG Institute
• Poole Hospital NHS Foundation Trust
• Queen Mary University of London
• Rady Children’s Hospital
• Rīga Stradiņš University Hospital, Latvia
• Robert Debré University Hospital, Paris
• Saint Anna Hospital, Torino
• Saint-Pierre University Hospital
• Saitama Medical University, Saitama Japan
• Samsung Medical Center, Seoul, South Korea
• Shinshu University School of Medicine
• Showa University
• Southern Illinois University School of Medicine
• St. Marianna University School of Medicine
• St. Louis Children’s Hospital
• Stanford University
• SUNY Downstate Medical Center
• The Ottawa Children’s Research Institute
• Thomas Jefferson University
• Tokyo Women’s Medical University
• Tufts Medical Center
• Uniformed Services, University of the Health Sciences
• University College Cork
• University College London Hospital
• University Hospital Agostino Gemelli, Rome
• University Hospital of Brooklyn
• University Medical Center Freiburg
• University Medical Center Utrecht
• University of Arizona
• University of Birmingham
• University of California, Davis
• University of California, San Diego
• University of California, San Francisco
• University of Colorado
• University of Florida
• University of Gothenberg, Sweden
• The University of Iowa
• University of Leuven
• University of Liverpool
• University of Lübeck
• University of Maryland
• University of Michigan
• University of Montreal
• University of North Carolina at Chapel Hill
• University of Oklahoma Sciences Center
• University of Otago, Christchurch
• University of Siena, Italy
• University of Tartu, Estonia
• University of Texas Southwestern Medical Center
• University of Ulm
• University of Utah
• University of Washington
• University of Wurzburg, Germany
• University of Zurich
• Vereniging van Ouders van Couveusekinderen (VOC)
• Vermont Oxford Network
• Yonsei University College of Medicine

Institute for Advanced Clinical Trials for Children

• Advocate Children’s Hospital – Oak Lawn
• Advocate Children’s Hospital – Park Ridge
• Ann and Lurie Children’s Hospital
• Children’s Hospital of Orange County
• Children’s Hospital of Philadelphia
• Children’s Mercy Hospital
• Children’s National Hospital
• Cleveland Clinic Children’s
• Hennepin County Medical Center
• Johns Hopkins University-Baltimore
• Le Bonheur Children’s Hospital
• Lucile Packard Children’s Hospital
• Medstar Medical Center
• Nationwide Children’s Hospital
• Nemours Children’s Specialty Care, Delaware
• Nemours Children’s Specialty Care, Jacksonville FL
• Orlando Health-Arnold Palmer Children’s Hospital
• Prisma Health Children’s Hospital
• Rhode Island Hospital/Hasbro Children’s
• Riley Children’s Hospital
• Rutgers-Robert Wood Johnson Medical School
• Tufts-Baystate Children’s Hospital
• Texas Children’s
• University of Colorado
• University of Louisville-Norton Children’s Hospital
• University of New Mexico Health Sciences Center
• University of Texas Health Sciences
• University of Utah
• VCU Children’s Hospital
• West Virginia University Children’s Hospital
• Yale New Haven Hospital

Team

Co-Directors

INC Team

C-Path Team