International Neonatal Consortium

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.

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.

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.

INC has established a robust infrastructure to gather and curate neonatal data from multiple sources, including:

• Electronic Health Records (EHRs): Data from 17 hospitals and 5 international sites.
• Registries and Observational Studies: Comprehensive datasets to support real-world evidence (RWE) generation.
• Collaborations: Partnerships with leading institutions like CHOP, Tufts, and Lurie Children’s Hospital.

To date, we have engaged with over 65 contributors and executed 30 Data Contribution Agreements (DCAs). Our data collection efforts are largely disease-agnostic, encompassing a wide range of neonatal conditions to ensure broad applicability across clinical and research needs.

Our RWD efforts are directed at creating actionable insights to enhance neonatal health outcomes. Key initiatives include:

• Neonatal Lab Value Reference Ranges: Establishing standard reference intervals through advanced statistical models like refineR.
• Predictive Modeling for BPD: Leveraging INC’s Real-World Data Analytics Platform (RW-DAP) to address critical challenges in Bronchopulmonary Dysplasia (BPD), a devastating complication of prematurity. With no new approved therapies in over 30 years, our efforts focus on:
• Trial Simulations for Clinical Efficiency: Using RWD to simulate clinical trials, optimize designs, and create historical external controls.

These efforts aim to improve survival rates, reduce long-term complications, and address the unmet needs in BPD care, which contribute significantly to healthcare costs. While initially focused on BPD, the tools and insights generated are designed to be disease-agnostic, enabling broader applications across neonatal drug development.

Our RW-DAP initiative envisions a future where neonatal care is transformed through data-driven insights and innovative solutions:

• Scalable Model-Informed Drug Development (MIDD): The MIDD process we employ to create Drug Development Tools (DDTs) is inherently adaptable. By leveraging our largely disease-agnostic data collection, this process can be easily applied to other neonatal disease areas, fostering innovation and efficiency across the spectrum of neonatal drug development.
• AI-Powered Analytics: Harnessing machine learning to detect patterns and predict outcomes.
• Accessible Data Platforms: Ensuring that curated data supports global research and regulatory needs.

INC’s RWD initiatives are shaping the future of neonatal care by:

Empowering regulatory science with robust data tools.

Personalizing treatment strategies through biomarker discovery.

Enhancing clinical trial efficiency with predictive models.

Promoting equitable healthcare outcomes by including diverse patient demographics.

Contact Us

For more information about our RWD initiatives and how to get involved, please contact us.

Our mission is to leverage advancements in regenerative medicine, including gene therapies, in-vivo gene editing, and cell therapies, to improve outcomes for neonates and young children. By integrating data, fostering collaboration, and addressing key challenges, the INC Cell and Gene Therapy Workgroup aims to pioneer new standards in therapeutic development for this vulnerable population.

1. Comprehensive Data Integration:

• Leverage Real-World Data (RWD) from clinical trials, patient registries, and longitudinal studies to inform study designs.
• Aggregate and standardize data from diverse sources to create a robust, analyzable dataset for regenerative therapy development.

2. Innovative Drug Development Tools:

• Develop safety assessment tools, trial design optimization methods, and advanced modeling solutions tailored for neonatal and pediatric populations.
• Address challenges such as small patient populations and dynamic disease progression through innovative approaches.

3. Regulatory and Ethical Considerations:

• Ensure compliance with regulatory standards while addressing ethical issues, including informed parental consent and equitable access.
• Develop strategies for long-term follow-up and assess safety and efficacy in global trials.

4. Collaborative Engagement:

• Foster dialogue among stakeholders, including regulators, patient advocates, industry leaders, and academic researchers, to harness collective expertise.
• Promote knowledge sharing through workshops, peer-reviewed publications, and public forums.

Gene therapies for conditions requiring early intervention demand careful consideration of the unique physiological, genetic, and developmental characteristics of neonates and young children. These therapies often necessitate:

Safety First: Rigorous assessment of delivery mechanisms like adeno-associated viral (AAV) vectors.

Tailored Solutions: Adapting therapies for diverse patient populations and genetic profiles.

Ethical Practices: Ensuring parental consent, equitable access, and consideration of long-term impacts.

Over a three-year timeline, the workgroup aims to achieve the following:

1. Data Platform Development:

• • Integrate and curate RWD from over 340,000 neonatal and pediatric patient records for regenerative therapy research.

2. Advanced Trial Design Strategies:

• • Utilize RWD to create external historical controls, reducing patient recruitment burdens and enhancing trial efficiency.

3. Regulatory Alignment:

• • Collaborate with regulatory bodies to ensure the reliability of models and tools for clinical trial designs and therapeutic approvals.

4. Dissemination of Knowledge:

• • Publish findings on safety, trial design, biomarkers, and ethical considerations to inform future research and regulatory practices.

The INC Cell and Gene Therapy Workgroup will significantly impact drug development by:

• Accelerating Therapeutic Development: Streamlining clinical trials using innovative designs and robust data.
• Enhancing Safety Standards: Addressing risk/benefit assessments and ensuring ethical practices in neonatal populations.
• Advancing Precision Medicine: Developing tools for patient stratification and outcome optimization.
• Pioneering Long-Term Solutions: Setting new benchmarks for global trials and therapy accessibility

INC welcomes stakeholders from academia, industry, regulatory agencies, and patient advocacy groups to contribute to this transformative initiative. Together, we can redefine the future of cell and gene therapies for early childhood.

For more information about INC’s Cell and Gene Therapy Workgroup, please contact us.

1. Stakeholder Engagement & Gap Analysis

• Promoting multi-stakeholder collaboration, including academic centers, industry sponsors, patient advocacy groups, regulators, and data stewards
• Convening expert focus groups and working sessions to align on priority unmet needs, data availability, methodological standards, and regulatory expectations
• Conducting structured gap analysis to assess limitations of existing HIE trial designs, current endpoints, and early markers of efficacy
• Developing an industry position paper co-authored by Taskforce members to articulate shared challenges, outline the need for improved early markers and trial enrichment strategies in HIE, and propose a roadmap for collaborative solution development and regulatory alignment

2. Data Curation & Integration

• Curation and harmonization of high-quality datasets containing neonatal imaging, clinical variables, and linked neurodevelopmental outcomes at 18–24 months or beyond
• Updating and expanding the Real-World Data and Analytics Platform (RW-DAP) with curated, structured data relevant to HIE and early brain injury
• Accessing and integrating additional de-identified, patient-level data from completed clinical trials, real-world datasets, and academic consortia (e.g., NICHD DASH, institutional repositories)
• Ensuring standardization of outcome definitions and alignment across datasets to enable pooled analyses

3. Modeling & Tool Development

• Developing and validating prognostic models using early clinical and/or imaging data (e.g., MRI-derived markers) to predict long-term neurodevelopmental outcomes
• Constructing clinical trial enrichment tools to support more targeted trial enrollment based on baseline risk profiles
• Exploring early biological markers (e.g., MRI-based, EEG, or blood-based) as potential exploratory endpoints for use in early-phase trials
• Using simulation frameworks to evaluate how these tools impact trial power, sample size, and efficiency under various design scenarios
• Documenting model performance (e.g., AUROC, calibration, subgroup performance) for future regulatory alignment

4. Regulatory Strategy & Tool Advancement

• Evaluating potential regulatory pathways for biomarker or tool endorsement through FDA’s Letter of Support, Fit-for-Purpose Initiative, or Biomarker Qualification Program
• Defining acceptable Contexts of Use (COU) for tools based on their validated performance, clinical utility, and level of regulatory evidence
• Developing a position paper to summarize Taskforce goals, early findings, and a proposed path forward for HIE drug development tools

5. Communication & Dissemination

• Publishing peer-reviewed manuscripts to share methodology, model results, and scientific conclusions
• Co-hosting a workshop or public conference to engage external experts, gather feedback, and build consensus across the neonatal research ecosystem

By focusing on a defined but flexible scope, the HIE Taskforce aims to deliver practical, high-impact tools that address critical gaps in neonatal drug development. Through the integration of curated clinical trial and real-world data, structured stakeholder engagement, and targeted modeling efforts, the Taskforce will support the development of tools that are both scientifically robust and aligned with regulatory expectations.

For more information about INC’s Neonatal Brain Injury and Hypoxic-Ischemic Encephalopathy working group, please contact us.

Create a roadmap towards establishing a measure that accurately and reproducibly evaluates acute pain in neonates that is capable of being used to support neonatal analgesic drug development

• The INC convened a global group of experts to develop consensus recommendations for neonatal seizure trial designs, including:​
  • Neonate-specific adaptive trial designs tailored to their unique physiology.​
  • Guidelines on inclusion/exclusion criteria, safety monitoring, and outcome measures.​
  • A focus on designing trials with reduced sample sizes, incorporating pharmacokinetic (PK) analysis, and randomization methods for accurate data.​

Outcome:​

• These recommendations are a foundation for developing a Master Protocol to evaluate multiple ASDs, facilitating more efficient and ethically sound clinical trials.​
• The guidelines have advanced regulatory pathways by providing structured methods to improve the safety and efficacy of ASD trials in neonates, potentially leading to better treatments and outcomes for this vulnerable population.

• Courageous Steps
• Hope for HIE
• March of Dimes
• NEC Society
• NICU Parent Network
• Nurtured by Design
• Preemie World
• Speaking for Moms & Babies, Inc.

• Council of International Neonatal Nurses (COINN)
• National Association of Neonatal Nurses

• Airway Therapeutics
• Bayer
• Chiesi
• Lilly
• Johnson & Johnson
• Novartis
• Oak Hill Bio (OHB)
• Pfizer
• Sanofi

• 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)

• 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 St George’s
• 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