Critical Path Institute Announces New Board Members Bonnie A. Allin and Louis Breton
Critical Path Institute (C-Path) today announced the appointments of Bonnie A. Allin and Louis Breton to its Board of Directors.
Launched on May 19, 2015, INC is a global collaboration formed to forge a predictable regulatory path for advancing the safety and effectiveness of therapies for neonates across the world.
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.
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:
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:
Day 1, October 19, 2021
2021 INC Annual Meeting | Session I | Cell and Gene Therapies
2021 INC Annual Meeting | Session II | Genetic Testing Technologies
Day 2, October 20, 2021
2021 INC Annual Meeting | Session III | Real-world Data
2021 INC Annual Meeting | Session II | Genetic Testing Technologies
The following communications tools are categorized and created for the INC stakeholders listed below. The key messages, logos, one pagers and social graphics contained or linked in the guide and on this page are intended to be used as is to keep messages about INC and its topics, i.e., NAESS, long-term outcomes, neonatal seizures, etc. consistent. If you’d like to make modifications, please email incinfo@c-path.org with your requests/ideas. The sample social copy included in the Social Toolkits can be modified to be written in your “voice” as needed. Please reach out with any questions. Thank you.
Parent Key Messages
Laboratory Values in Neonates
Neonatal Adverse Event Severity Scale (NAESS)
Long-term Outcomes
Neonatal Seizure
Culture of Research Communication in NICUs
Parent Communication Guide
Parent Social Media Toolkit
Parent Key Message Slides
Neonatologists Key Messages
Laboratory Values in Neonates
Neonatal Adverse Event Severity Scale (NAESS)
Long-term Outcomes
Neonatal Seizures
Two general messages regarding neonatal drug development not specific to seizures:
Four key messages related to therapeutic trials for neonatal seizures:
Culture of Research Communication in NICUs
The INC survey asked neonatologists, nurses, and parents about their personal perspectives on research-related education and communication practices in the NICUs across the globe (https://www.nature.com/articles/s41372-021-01220-5.pdf)
Neonatologist Communication Guide
Neonatologist Social Media Toolkit
Neonatologist Key Message Slides
Nurse Key Messages
Laboratory Values in Neonates
Neonatal Adverse Event Severity Scale (NAESS)
Long-term Outcomes
Neonatal Seizures
Nurses played a key role in the development and review of this document, and nurses are often the initial members to recognize neonatal seizures, thus nurses support the following:
Culture of Research Communication in NICUs
Nurses played a key role in the development of the culture of research survey and were the majority respondents to the survey. Based on those responses this paper and nursing key messages were developed. We would like to highlight the following messages that relate to the nursing community:
Nurse Communication Guide
Nurse Social Media Toolkit
Nurse Key Message Slides
Regulators Key Messages
Laboratory Values in Neonates
Neonatal Adverse Event Severity Scale (NAESS)
Long-term Outcomes
Neonatal Seizures
Culture of Research Communication in NICUs
Regulators Communication Guide
Regulators Social Media Toolkit
Regulators Key Message Slides
Industry Key Messages
Laboratory Values in Neonates
Neonatal Adverse Event Severity Scale (NAESS)
Long-term Outcomes
Neonatal Seizures
Culture of Research Communication in NICUs
Industry Communication Guide
Industry Social Media Toolkit
Industry Key Message Slides
Neonates have long been considered “therapeutic orphans” with the vast majority of drugs being used in an off-label capacity for this group. Additionally, the last drug that significantly impacted survival in premature neonates was approved more than 30 years ago. The reasons behind this are multifactorial, ranging from lack of sufficient understanding of how temporal changes in neonatal physiology impact drug development, lack of standardized methods to evaluate adverse events in the neonatal population and insufficient multidisciplinary engagement with key stakeholders in NICU environment, etc. In order to address these issues, INC was established in 2015 as a public-private partnership within the construct of Critical Path Institute with the mission of advancing unmet drug development needs in the neonatal population.
INC concentrates its efforts on those conditions most commonly encountered in the Neonatal Intensive Care Units (NICUs). We operate as a pre-competitive collaborative partnership of diverse stakeholders, consisting of industry members, academic researchers, nurses, families and regulators to address the measurement and assessment of clinical outcomes in neonates, through teams that share data and expertise to advance regulatory science, and improve the predictability of neonatal drug development. Individual investigators or organizations do not possess the requisite data, resources, or expertise to tackle the gaps in regulatory science for neonates. Through direct engagement with regulators, the consortium forges a predictable regulatory path for evaluating the safety and efficacy of therapies for neonates.
INC is truly an international consortium. We have membership consisting of representatives global regulatory agencies (FDA, EMA, PMDA, MHRA, and Health Canada), pharmaceutical companies (Pfizer, Bayer, Chiesi, Sanofi, Eli Lilly and Company, Johnson & Johnson, Takeda, Novartis and Trove Therapeutics), nursing organizations, parents and family advocacy organizations and academic institutions from USA, Canada, UK, Europe, Japan and Australia.
A multidisciplinary working group identified key issues in the role of assessment of LTO in neonatal clinical trials and made recommendations about optimal approaches to LTO assessments in therapeutic trials in newborns. These recommendations can be incorporated into clinical trial protocol design by sponsors and investigators with input of parents, nurses, health care providers and other key stakeholders.
Adverse or beneficial effects of therapeutic interventions may not appear until after a study’s completion making long-term follow-up imperative. In order to improve outcomes and ensure patient safety, long-term follow-up needs to balance direct and indirect family costs against the potential benefit of more detailed information.
INC supports long-term outcome assessments in neonatal trials to evaluate the long-term safety and efficacy of neonatal treatments during early childhood. The INC brought together physicians, nurses, parents, and representatives of regulatory agencies and industry to summarize their joint considerations for LTO assessments in clinical research studies in neonates. They summarize different approaches to LTO assessments while also acknowledging that LTO assessments can be time-consuming for families and research staff.
The NAESS was developed within the International Neonatal Consortium (INC). Throughout the NAESS development, input was obtained from multiple key stakeholders involved in neonatal care and drug development. The stakeholders included academic and non-academic clinicians and researchers, neonatal nurses, parents, as well as representatives from industry, regulatory agencies, and funding organizations from Canada, Europe, Japan and USA. Respondent and participant groups were expanded at every round to incorporate feedback from a maximal number of stakeholders.
Standardized adverse event (AE) severity scales have been developed for older children and adults, but they are not suitable for use in neonates. Assessing AE severity helps determine the importance of the AE in the clinical setting. Standardization of AE severity criteria could make safety information more reliable and comparable across trials. The development of a neonatal specific AE severity scale facilitates the conduct and interpretation of neonatal clinical trials. The use of the NAESS can improve the quality of drug and device safety evaluations and can facilitate the conduct of neonatal clinical trials.
The NAESS tool is available publicly on the NCI Thesaurus. To ensure data standards are consistent across trials, the terminology is harmonized and mapped to NICHD Pediatric AE terminology and MedDRA lowest level terms. Over time, this online resource will be updated to include a broader list of conditions. The INC is supporting the research that will validate the use of the NAESS tool. We are excited to see the NAESS incorporated into the design and conduct of neonatal trials and the continued expansion of specific adverse event terms within this tool. For more information, see the recently published article link: Inter-rater reliability of the neonatal adverse event severity scale using real-world Neonatal clinical trial data | Journal of Perinatology (nature.com).
The INC brought together physicians, nurses, parents, and representatives of regulatory agencies and industry to define the key components of research trials for treatment of neonatal seizures. This collaborative approach led to standard definitions for the most critical aspects of a research trial including who is eligible for a trial, definitions of seizure and seizure burden, what outcomes to measure, and the ethical considerations regarding comparator medications versus placebo.
Seizures are more common in neonates than any other age group and they are difficult to treat. Research studies are needed to develop new treatments but it is difficult to successfully perform such studies in neonates. These standardized recommendations help expedite clinical research to efficiently determine if a medication is safe and effective by providing the key elements of a research protocol. These recommendations also provide the essential elements of a “master protocol” through which multiple medications could be studied over time in neonates with seizures.
For information on how to get involved with INC, please email incinfo@c-path.org.
Jonathan Davis
Professor of Pediatrics, Tufts University
Deb Discenza
Founder and CEO, PreemieWorld
Jennifer Degl
Speaking for Moms and Babies, Inc
Wakako Eklund
Advance Neonatal Solutions. L.L.C.
Carole Kenner
Chief Executive Officer, Council of International Neonatal Nurses, Inc. (COINN)
Thomas Miller
VP and Global Head, Pediatrics, Bayer
Mark Turner
Senior Lecturer in Neonatology, University of Liverpool
Kanwaljit Singh, MD, MPH
Executive Director, INC
Christine Barry, MPH
Senior Project Manager, INC
Olivia Giola
Project Coordinator, Pediatrics
Klaus Romero, MD, MS, FCP
Chief Executive Officer, Chief Science Officer, Executive Director of Clinical Pharmacology
Collin Hovinga, PharmD, MS,
FCCP, Vice President, Rare and Orphan Disease Programs
Rick Liwski
Chief Technology Officer and Data Collaboration Center Director
Lewis Barbieri, JD
Director of Contracts
Jagdeep Podichetty, PhD
Director, Predictive Analysis
Ramona Walls, PhD
Executive Director, Data Science
Nicole Vasilevsky, PhD
Associate Director of Data Science
Bob Stafford, MA
Data Management Team Lead, DCC
Keith Scollick
Cloud Platform Engineer
Will Roddy
Data Engineer Team Lead, DCC
Ian Braun
Data Engineer
Dan Hartley, MS
Data Manager II