Building Better Paediatric Clinical Trials

Paediatric clinical trials remain difficult to plan and execute. Children need treatments supported by evidence from their own age groups, yet research investment, trial infrastructure, and regulatory coordination have not kept pace with that need.

What must the industry change? Protecting children requires better-designed studies and a stronger global commitment to clinical paediatric evidence.

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Why Do Paediatric Clinical Trials Still Fall Short?

Children are not simply smaller adults. Their organs, metabolism, immune systems, and drug responses change throughout development.

A medicine that works safely in an adult may behave differently in a newborn, infant, or adolescent.

Doses, formulations, treatment schedules, and adverse event profiles all require careful assessment.

Yet many medicines used in paediatric care lack robust evidence from trials involving children. Clinicians may have to rely on adult data, limited paediatric studies, or experience with off-label prescribing.

This creates uncertainty for healthcare professionals and families. It can also leave children exposed to treatments with unclear optimal doses, safety profiles, or long-term effects.

The problem is not simply a shortage of individual studies. It reflects weaknesses across the paediatric clinical research ecosystem.

So how can we strengthen the paediatric clinical trial ecosystem to better inform policy and programmes?

Some meticulous research draws on work from the World Health Organization’s Global Clinical Trials Forum. Its Paediatric Clinical Trials Working Group brought together specialists across infectious diseases, nutrition, neonatology, pharmacology, oncology, neurodevelopment, public health, and policy.

The research group identified a system that often fails to align research priorities, funding, infrastructure, and community needs.

Children remain marginalised in clinical research, despite the long-term consequences of childhood illness. Gaps in evidence can affect health throughout life, while also influencing education, productivity, and wider social outcomes.

There are also large commercial, ethical, and operational barriers that hold back paediatric development.

Underinvestment, complex regulatory requirements, and a lack of well-controlled trials all pose challenges for paediatric clinical trials.

There is a worrying industry trend that some sponsors have closed dedicated paediatric development centres or shifted resources towards markets with stronger commercial returns.

Together, these limitations expose a difficult contradiction. The industry recognises that children need age-appropriate medicines, but the systems responsible for developing those treatments still struggle to support the research.

The result is an evidence gap that cannot be solved by making more robust regulatory requirements.

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A Global Ecosystem Needs Shared Priorities

Paediatric research needs better coordination at global, regional, and national levels.

To achieve this, the industry should focus on aligning priorities, tracking investment, improving infrastructure, and supporting regional trial networks.

Consideration should recognise that paediatric research often involves small or dispersed patient populations.

Rare childhood diseases may affect relatively few patients in any one country. Other conditions carry a high disease burden in regions where research infrastructure and funding remain limited.

Individual institutions may lack the patient numbers, specialist expertise, or financial resources to conduct meaningful trials alone.

To address this challenge, regional consortia can help address this problem by connecting hospitals, researchers, sponsors, and public health organisations.

This approach can also improve the relevance of research. A trial designed around the disease burden and healthcare systems of one high-income country may not answer the questions facing clinicians elsewhere.

Regional collaboration can bring local priorities into study design and make results more useful across different populations.

Additionally, there should be transparency about the links between funding decisions and identified child health priorities.

This requires that institutions monitor where investment goes, which populations remain underserved, and whether funded studies produce evidence that informs policy and clinical practice.

Partnerships with academic centres, public health organisations, paediatric hospitals, and regional research networks can help sponsors reach populations that conventional development models often overlook.

The WHO’s clinical trials information for children also reinforces the importance of transparent registration and accessible evidence.

Better visibility helps clinicians, researchers, and policymakers understand which studies are underway and where knowledge gaps remain.

In other words, a coordinated ecosystem can make paediatric research more efficient, relevant, and equitable.

It can also reduce duplication and help funders direct resources towards questions that matter most.

Better Trial Design Reduces Burden Without Weakening Evidence

There are several approaches that could improve paediatric drug development.

These include artificial intelligence, modelling and simulation, innovative trial designs, real-world data, and stronger public-private partnerships.

The tools are not substitutes for sound clinical evidence. Their value lies in helping researchers make better decisions, use available information more effectively, and avoid unnecessary demands on children and their families.

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Modelling and simulation

Children change as they grow. Drug absorption, distribution, metabolism, and elimination can differ substantially between age groups.

Researchers therefore need methods that account for developmental changes when selecting doses and planning studies.

Model-informed approaches can combine existing adult data, paediatric pharmacology, and information from earlier studies to support dose selection and trial design.

Physiologically based pharmacokinetic modelling and population pharmacokinetic analysis can help researchers predict how a medicine behaves across different ages.

These methods can reduce uncertainty before researchers expose children to an investigational treatment. They can also help identify which age groups need dedicated study and where additional clinical data remain essential.

Innovative trial designs

Traditional trial designs do not always suit small paediatric populations.

Recruitment can be slow, and splitting a limited number of participants across several treatment arms can weaken statistical power.

Adaptive designs, Bayesian methods, and carefully planned use of external evidence can help researchers address some of these difficulties.

They still require clear assumptions, appropriate controls, and robust statistical oversight.

The objective is not to lower evidence standards, but rather to design studies that answer important questions with fewer avoidable delays and less unnecessary participant burden.

Real-world data and artificial intelligence

Electronic health records (EHR), disease registries, and other real-world data sources can help researchers understand disease patterns, identify potential participants, and examine treatment use outside controlled trials.

AI tools may support data analysis, recruitment, and the identification of relevant clinical patterns.

However, paediatric datasets are often limited, fragmented, or unrepresentative. Algorithms trained on incomplete data can reinforce existing gaps rather than resolve them.

Sponsors must therefore assess data quality, age representation, privacy, and bias before relying on these technologies.

Real-world evidence can complement clinical trials, but it does not automatically establish causality or replace prospective evidence where that evidence is needed.

Pharmatica has previously examined the operational side of these technologies in our coverage of using EHR for patient recruitment and recruitment prediction in clinical trials. The same principles apply in paediatric research.

Technology only creates value when teams integrate it into sound study design and clinical workflows.

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Industry Must Treat Paediatric Development as Core R&D

The commercial case for paediatric development is not always straightforward.

Patient populations can be small, recruitment can be difficult, and development programmes may require additional formulations, age-specific dosing studies, and longer follow-up.

These factors can make paediatric programmes less attractive within conventional portfolio models, and this imbalance contributes to underinvestment and the loss of dedicated expertise.

However, treating paediatric research as a secondary activity creates costs of its own. It leaves clinicians with incomplete evidence, delays the availability of age-appropriate treatments, and can lead to repeated studies that address similar questions without building a coherent evidence base.

Regulatory incentives have an important role, but they cannot carry the full responsibility. Sustainable progress needs long-term investment, experienced paediatric development teams, and collaboration between sponsors, regulators, researchers, and patient organisations.

Public-private partnerships can help share the financial and operational burden. They can support studies in areas where commercial incentives alone do not attract sufficient investment.

Advocacy groups also bring knowledge of patient and family priorities, helping sponsors understand practical barriers to participation and treatment access.

Children and families should have a meaningful role in shaping research.

Age-appropriate communication, caregiver involvement, and clear explanations of study procedures help make participation more informed and respectful.

Researchers should also consider the practical demands that trials place on families, including travel, time away from school, and access to specialist centres.

The ethical framework must remain central. Children need additional protections, including appropriate parental or guardian permission and the child's assent when they have the capacity to understand the decision.

The U.S. Food and Drug Administration’s paediatric ethics guidance outlines the agency’s approach to scientific and ethical oversight in studies involving children.

Ethical protection and meaningful inclusion are not opposing goals. The challenge is to design research that minimises risk while producing evidence children need.

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What Must Stronger Paediatric Clinical Trials Deliver?

Approaching World Children’s Day on 20 November, there must be strong recognition of children’s rights and the importance of listening to their experiences.

In clinical development, that commitment must extend to the evidence used to make decisions about their care.

There is a more coordinated model. Global and regional institutions need to align priorities and investment.

Sponsors need to sustain paediatric expertise and build partnerships and researchers need to use modern methods without weakening scientific standards.

Families and young people need a meaningful voice in the process.

For sponsors, paediatric development should be considered early in portfolio planning, not treated as a late regulatory exercise.

This means identifying age-specific evidence needs, planning suitable formulations, assessing recruitment feasibility, and building long-term follow-up into development strategies.

Progress should also be measured through practical outcomes including better representation of children in relevant studies, fewer evidence gaps, stronger regional research capacity, and more medicines supported by appropriate paediatric data.

Paediatric research demonstrates why progress depends on investment, coordination, and a commitment to the populations that clinical research has historically underserved.

At Pharmatica, we examine the clinical research strategies, evidence systems, and partnerships shaping the future of pharmaceutical development.

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