Promoting Global Clinical Research in Children

Promoting Global Clinical Research in Children

The development and administration of safe and effective therapeutic products for children is critical to the health of a population. Global innovations in pediatric drug development are essential to mitigate the myriad of practical challenges of executing multinational clinical trials, address regulatory challenges of working across jurisdictions, and ensure consideration of ethical approaches to enrolling children in research.

Medicines—including drugs, biologics, and devices—must be more frequently, rigorously, and carefully evaluated for safety and efficacy in the global pediatric population. This vision depends, in part, on identifying and overcoming existing barriers to conducting multi-regional pediatric trials, and then motivating their enrollment, conduct, and completion. Pediatric patients deserve, as all patients do, therapeutic products for which adequate safety and efficacy data have been rigorously collected.

Our commitment to advancing global pediatric clinical trials remains steadfast through the identification of challenges and the development of solutions to critical barriers, and our foci continue to evolve to meet the ever-changing needs of the pediatric clinical trial landscape. To harmonize approaches globally, the MRCT Center initially convened a multistakeholder workgroup in 2019 representing academia, industry, regulators, non-profits, trial networks, patients, and advocates.

With significant progress made to date, we continue to explore key aspects of pediatric product development and clinical trials, share findings through an array of freely available and widely disseminated materials, and advance integral international collaborations. Our resources and materials include theIncluding Young People in Research toolkit, currently under revision with a release anticipated in early 2026, Guiding Principles, and a curated selection of pediatric-focused webinars, complete with recordings and summaries.

Our interactive webpage summarizes the work to date and links to key deliverables. Our current work focuses on pediatric platform trials—studies evaluating multiple investigational products simultaneously. An October 2024 workshop, attended by 80 global experts, identified gaps and strategies in three disease areas: major depressive disorder, oncology, and multidrug-resistant tuberculosis. In July 2025, the MRCT Center co-hosted a follow-on workshop focused on pediatric oncology to develop an implementation framework for academic–industry platform studies to support regulatory requirements (PIPs, iPSPs) and potential marketing authorization. That work continues with the finalization of a comprehensive toolkit that will support academic/industry collaborations for pediatric oncology platform trials, slated for release and dissemination in mid-2026.

Part 1: The Challenges

The MRCT Center’s Promoting Global Clinical Research in Children project sought to examine the ethical, regulatory, privacy, and confidentiality concerns that impede the conduct of global clinical trials in children, with a particular emphasis on ex-US countries and low- and middle-income countries (LMICs). Understanding the challenges encountered in conducting global pediatric clinical trials informed the direction of the work and the development of the project products.

The health of a population is reliant on the development and administration of safe and effective therapeutic products for children. Because children often face diseases that do not affect adults and metabolize and respond to treatments differently than adults, data from clinical research and/or health care involving adults cannot reliably and consistently be extrapolated to pediatric populations. Therefore, ensuring that children have access to safe and effective medicines is generally contingent upon the conduct of trials that enroll children. The incidence of many pediatric-specific conditions in children, however, is low, and the pool of potential pediatric research participants is often small and geographically dispersed. Thus, it is often necessary to conduct multisite and multinational pediatric studies to secure sufficient enrollment for study completion. Given the dearth of relevant data and the challenges of working across jurisdictions, the pressing need to overcome existing barriers to multinational pediatric research remains. Further, regulatory complexities render approval of product for children challenging, and once approved, access to and payment for medicines to pediatric populations must be enabled to ensure the availability of approved products to those who need them.

Associated Assets:

Part 2: Principles to Guide the Work

The array of starting tenets offered to guide the work with children and teenagers in support of the belief that children should be protected in and through research. Children should only be enrolled in research that follows established ethical principles. All ethical principles relevant to the conduct of clinical research in the general population also apply to pediatric clinical research. National health authorities should regulate pediatric clinical research in accordance with internationally accepted ethical principles (e.g., CIOMS). Children’s rights, as stated, for example, in ~~the~~ ~~UN Convention on the Rights of the Child~~, must be respected within the clinical research context. Evidence of potential for clinical benefit to the enrolled children must justify the risks of participation, especially when those risks are significantly greater than those encountered in everyday life. Additionally, children should only be enrolled in research that has scientific and social value related to the health of children or diseases that originate in childhood. The burdens of research participation should be minimized, and efforts to accommodate the needs of children and their families and caregivers should be undertaken to minimize harm and disruption. Importantly, throughout the research process, children are entitled to have a voice in making decisions to the extent their capacity allows. Taken in its entirety, these starting principles undergird the project foci.

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Part 3: Equitable Access

The larger body of project work supports the very basic premise that pediatric patients deserve equitable access to medicines. Children and their health needs are an important research priority, and this access includes safe and effective healthcare services, including vaccines, diagnostics, therapeutics, and disease prevention measures. There are ethical considerations to weigh, including that a child’s access to medicines (and healthcare) is often dependent on where that child lives. A product may be deemed safe and effective by a jurisdiction’s guiding regulatory body and the same jurisdiction’s health technology assessment body may determine that the product in question is not cost effective, thereby preventing access to that product. Children may take on the risks of participating in a clinical trial without benefit either to themselves or others if the interventional product is not available at the end of the trial to the population for whom it was intended. Investigators and sponsors have responsibilities to the child who has participated in research after the research has ended. This includes access to individual and overall research results, if desired, and post-trial access to the therapeutic intervention if found to benefit the child.

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Part 4: Unique Ethical Dilemmas Around the World

Research with children presents a number of unique ethical dilemmas despite the premise that research involving children follows the same ethical foundation of research involving adults—respect for persons, beneficence, non-maleficence, and justice. For example, children’s decisions are generally subject to the authority and influence of parents, guardians, and/or other authorities, which can complicate how to best consider, discern, and honor children’s preferences during the process of the adult (parent/guardian) providing permission for the minor child’s participation. Assessment of potential risks and benefits is especially challenging in the context of pediatric research, given that the burdens of trial participation may vary with a child’s age, maturity level, medical condition, and situational factors. Finally, some research that may be permissible among adults following their informed consent may not be permissible among children who cannot give informed, autonomous consent, even though assent is desired if not required.

Part 5: Regulatory and Governance Complexities

There are significant differences in country-specific regulations and/or guidance internationally that give rise to regulatory complexities, including the fact that guidance is a recommendation rather than a requirement, rendering practice even more discordant. Such complexities include issues of exploitation and vulnerability, ambiguity around the definition of minimal risk, inconsistencies in the required timing of pediatric development plans, and confusion regarding what constitutes undue inducement and coercion. That some countries do not have regulations or guidance addressing pediatric research at all, and that existing regulations are not harmonized, renders multi-national pediatric research difficult, burdensome, and sometimes impossible. The COVID-19 pandemic served as a pointed reminder highlighting the need for consideration and inclusion of children, improved efficiencies, and global cooperation.

Related Assets:

Part 6: Role of HTA Bodies

The clinical trial enterprise is fueled by the desire to provide access to medicines for children worldwide, and different stakeholders have different remits that together impact access. Regulators are charged with assessing a medicinal product for safety and efficacy independent of price, while Health Technology Assessment (HTA) bodies are charged with assessing individual and societal value considering not only the cost but also available alternatives. In many countries, the assessments of the HTA authorities of pediatric medicines determine access. The perspectives of regulators, industry, academia, clinicians, patients and patient advocates, and HTA bodies were considered in an effort to develop a common understanding of the evidentiary requirements that HTA bodies need to render a comprehensive value assessment for pediatric populations. The work to promote understanding of the different roles and responsibilities for patients, parents and caregivers, investigators, and the public is ongoing.

Related Assets:

A scoping review of challenges in pediatric health technology assessments with a focus on pharmaceutical interventions; DOI: 10.1017/S0266462325103188

Part 7: Elevating the Voices of Young People

The Promoting Global Clinical Research in Children project sought to collaboratively identify and propose solutions to various regulatory, ethical, and operational challenges encountered in the conduct of international pediatric clinical trials. Of the many topic areas discussed over the course of the effort, a consistent thread of dialogue, almost irrespective of the starting point of any particular discussion, was the importance of soliciting, hearing, respecting, and responding to the pediatric patient voice. While not routinely solicited or included in product development or the clinical research enterprise, there are meaningful ways to engage patients including children, adolescents, and their families. We continue to learn how to make research stronger and build public trust by including the youth perspective in a thoughtful, systematic, and representative way. To that end, an array of deliverables focused on amplifying the voice of children and adolescents has been produced, with more forthcoming.

Related Assets:

Part 8: Pediatric Platform Trials

In an ongoing effort to speed access to safe and effective medicines for pediatric populations, the MRCT Center began exploring alternative, innovative clinical study designs such as platform trials. Such studies, which evaluate more than one investigational product simultaneously, may offer substantial efficiencies if companies were able to collaborate on a shared trial infrastructure.

We began this effort by hosting a 2-day workshop in 2024, Advancing Pediatric Platform Trials: Streamlining Development, Maximizing Impact, that explored how multi-sponsor pediatric platform trials can be leveraged to speed the delivery of innovative therapies to pediatric patient populations in association with adult approval. Three diseases that model different challenges—major depressive disorder (MDD), multi-drug-resistant tuberculosis (MDR-TB), and pediatric oncology—were used to ground the discussions in real-world settings and illustrate different challenges.

Discussants successfully identified knowledge gaps and practical challenges that impact pediatric platform trial planning and execution. Each of the three disease-specific breakout sessions over the two-day event proposed actionable strategies to address the identified barriers and challenges.

The work continued with a deeper exploration into academic/industry collaborations in pediatric oncology. In late 2025, the MRCT Center co-hosted a follow-on workshop, Advancing Childhood Cancer Academic-Industry Collaborative Platform Trials: A multistakeholder workshop. The aim was to develop an implementation framework for academic-industry collaborative platform studies that deliver data that could support a regulatory requirement (PIPs, iPSPs) and potentially marketing authorization applications, specifically focused on pediatric oncology medicines.

A comprehensive toolkit serving as a blueprint for conducting this work is in development, with a mid-2026 release planned.

Related Assets:

Objectives

To identify the challenges related to decision making for individual children that impede the conduct of transnational pediatric clinical trials, including issues related to assent, consent, and inclusion of the voice of young people.
To address the lack of consensus and awareness on key issues around benefit and risk considerations that create barriers to and inefficiencies in transnational research with children.
To define and address the operational barriers to conducting transnational pediatric trials and propose solutions, including the promotion of a model of global pediatric regulatory cooperation.

Key Milestones

October 2025: Published “A scoping review of challenges in pediatric health technology assessments with a focus on pharmaceutical interventions.”
July 2025: Co-hosted a 2-day workshop, Advancing Childhood Cancer Academic-Industry Collaborative Platform Trials workshop in Washington, DC.
May 2025: Released Podcast “Advancing Pediatric Platform Trials – A Conversation with Dr. Danny Benjamin“
April 2025: Released workshop report “Advancing Pediatric Platform Trials“
November 2024: Published Engaging children and adolescents in the design and conduct of paediatric research
October 2024: Successfully hosted a 2-day workshop, “Advancing Pediatric Platform Trials: Streamlining Development, Maximizing Impact,” in Washington, DC
January 2024: A comprehensive interactive overview of the Pediatrics project and key deliverables was released.
March 2023: Released the Including Young People in Research toolkit.
March 2023: Hosted the fifth in the 5-part webinar series, Informing the Future.
November 2022: Hosted the fourth in the 5-part webinar series, Facilitating Pediatric Medicines Development: Models of Global Cooperation
June 2022: Hosted the third in the 5-part webinar series, Assent and Consent in the Field: Culture, Context, and Respect
April 2022: Release of 3 additional pediatric educational brochures for young people contemplating participation in a clinical trial; these proudly carry the iCAN Seal of Approval
February 2022: Hosted the second in the 5-part webinar series, Time to Listen: Hearing from Young People in Clinical Research
October 2021: Hosted the first in the 5-part webinar series, Advancing international Pediatric Clinical Research: Informing the future form COVID-19 Lessons Learned.
July 2021: Panel discussion at DIA-Pediatric engagement in research: Young people have a voice
March 2021: Dissemination of “Biobank” comic book, a collaboration of Boston Children’s Hospital, Harvard Catalyst and Precision Link
February 2021: Project focus pivots to deliverable preparation
January 2021: Received an FDA R13 scientific conference grant to support a series of meetings, “Global Cooperation to Promote Clinical Research in Children” to be hosted virtually during 2021-2022
December 2020: Panel Discussion at MRCT Center Annual Meeting–Emerging Issues in Global Pediatric Clinical Trials: Perspectives on patient/family/caregiver engagement
November 2020: Released “Assent to Consent” flyer which earned the iCAN (International Children’s Advisory Network) “Seal of Approval”
January 2020: Core leadership team in-person meetings
October 2019: Project launch with first work group meeting of diverse stakeholders

Project Leadership & Staff

Barbara E. Bierer, MD. Faculty Director, MRCT Center
Steven Joffe, MD, MPH. Chief, Division of Medical Ethics, Perelman School of Medicine at the University of Pennsylvania
Dominik Karres, MD, CPM. Paediatric Medicines Office, Scientific Evidence Generation Department, European Medicines Agency
Robert “Skip” Nelson, MD, PhD. Senior Director, Pediatric Drug Development, Johnson & Johnson
Lisa Koppelman, MSW, LICSW, MPH. Program and Team Director, MRCT Center
Trevor Baker, MS. Program Manager, MRCT Center
Lauren Otterman, MBHL. Project Manager, MRCT Center

CLINICAL TRIALS & RESEARCH

Promoting Global Clinical Research in Children