Optimizing Pediatric Trials for High-Quality Data: Scientific Insights, Practical Approaches, and Expert Perspectives

Pediatric clinical research stands at crossroads, guided by evolving regulation, advancing digital tools, and a renewed commitment to evidence that is both scientifically robust and child centered.  

The EU Pediatric Regulation (2007) and the US Pediatric Research Equity Act have set the expectation that children must no longer be “therapeutic orphans,” neglected in the generation of high-quality data. Instead, children are now recognized as unique participants, requiring innovative approaches throughout the entire trial process.

Why Pediatric Trials Demand Specialized Strategy

Pediatric populations present distinct challenges, ethically, scientifically, and operationally. Children often enter research studies brought by their caregivers, not as independent volunteers. Their cognitive capabilities, emotional states, and willingness to collaborate vary by age and developmental stage. As Dr. Joan Busner, Clinical Vice President at Signant Health, explicitly states: 

“Pediatric clinical trials offer unique challenges. They are often associated with the highest placebo response rates. Clinical outcome assessments are complicated by different age-appropriate versions and observer versions. And obtaining consent and assent is a more complex process.” 

Children’s disease manifestations can differ dramatically from those in adults, making it essential to avoid simply importing adult endpoints. As Dr. Busner further emphasizes: 

It is essential that measures, consent tools, and procedures be understandable and suited to the child’s age and capabilities. The goal is to make the child feel like a partner in the research, ensuring active family participation and quality data collection.
 

Key Focus Areas for Sponsors 

1. Deep Disease Understanding and Meaningful Endpoints

Endpoints must be selected and validated specifically for the pediatric age, disease state, and level of cognition. It is critical to assess who provides the information that forms the study data, that is, whether outcomes are reported directly by the child (self-report), by a caregiver (observer-report), or by both, and what method is used to gather those responses (for instance, interviews, electronic diaries, or clinical evaluation tools). Rare diseases and severe conditions may require remote or home-based sampling and unique endpoint adaptation. 

To learn how Signant has directly supported regulatory success in rare pediatric disease trials, see the endpoint reliability case study” Rescuing Rare Pediatric Disease Trials

2. Reducing Family and Participant Burden 

Trials must be designed with logistics in mind. Reduce unnecessary travel through decentralized trial models, enable flexible assessments (including home visits and telemedicine), and address physical or psychiatric needs (e.g., using topical anesthetics for needle procedures or minimizing venipuncture frequency). 

3. eCOA and Age-Appropriate Technology

Robust eCOA platforms provide interactive, multimedia-rich experiences (videos, avatars, cartoons) that are accessible and understandable for children at every developmental stage. Electronic diaries and international seizure diaries, for example, are critical tools in disorders like epilepsy. Digital tools should offer support through reminders, standardized rater guides, and adaptability across languages and cultures. 

For sponsors interested in seeing how age-appropriate electronic scale implementation and rater standardization raise data quality in pediatric trials, Signant Health’s recent blog on electronic CDRS-R assessment provides detailed, practical examples.

4. Managing Placebo Response and Data Noise

Pediatric trials experience elevated placebo responses, often amplified by social compliance and attempts to please investigators. Dr. Busner underlines that, “Heightened scrutiny at every stage, from consent and data collection to endpoint selection and family engagement,” is vital for trial integrity. Standardized rater training, careful design of observer and investigator roles, and rigorous data checks are essential to control bias and variance. 

5. Comprehensive Staff Training and Neutral Engagement 

It is crucial to train site staff to maintain warmth and empathy while remaining neutral and standardized in assessments, especially in rare disease research where long-term relationships may compromise objectivity. Sensitivity to differing levels of experience across sites must be proactively managed to avoid resistance to standardized protocols. 

Implementation Recommendations

• Develop and validate endpoints that directly reflect pediatric disease, age, and context.

• Prioritize direct patient (PRO) and observer (ObsRO) reports using age- and culturally- validated tools, following best practices such as those outlined in the latest guidelines on measure selection and implementation. In pediatric studies, ObsROs are frequently completed by caregivers or parents, who report based on directly observable signs or behaviors. 

To learn more about selecting the right patient- and observer-reported measures for pediatric trials, see the concise recommendations in PROs and ObsROs in Pediatric Clinical Trials: Measure Selection and Implementation

• Deploy age-appropriate eCOA solutions with robust training and support for investigators and raters, emphasizing neutrality, clarity, and bias reduction.

• Document every adaptation, translation, and process rigorously for regulatory readiness and global scalability.

• Engage children and families as collaborators, not merely as subjects, ensuring every measure, process, and technology makes them feel empowered and understood. 

Conclusion: A New Standard for Child-Focused Clinical Trials 

The privilege of working with children and families in clinical research brings with it a profound ethical and scientific responsibility. Delivering high-quality pediatric data depends on disease-specific knowledge, validated child-centric tools, flexible trial operations, and unwavering regulatory compliance. Dr. Busner’s guidance, placing the child’s comprehension and engagement at the heart of trial design, should be the foundation for every sponsor’s pediatric research program. 

Empowering the pediatric voice and generating regulatory-grade data is not only possible; it is essential for global advances in child health. 

If you are ready to elevate your pediatric clinical trials with scientifically validated tools, operational expertise, and a child-focused digital strategy, connect with our experts or explore Signant Health’s dedicated pediatric trial resources. Let us advance the standard and deliver better evidence for children together.

About the Authors

	Dr. Figueroa is a Clinical Scientist with the eCOA Science Team at Signant Health, where she leverages her extensive expertise in electronic Clinical Outcome Assessments (eCOA) across diverse therapeutic areas, including oncology, dermatology, and infectious diseases. With over a decade of translational research experience, Dr. Figueroa is dedicated to advancing the field of clinical trials and improving patient outcomes through innovative methodologies and strategic insights. Her work at Signant Health focuses on integrating cutting-edge eCOA technologies to enhance the accuracy and reliability of clinical data, ultimately contributing to more effective and patient-centric healthcare solutions.
	Samantha Silverman holds Master's degrees in Health Psychology and Public Health. She joined Signant Health in 2013 and serves as both a Senior Clinical Scientist and eCOA Clinical Scientist in the Digital Health Science Department. In her dual role, she works across various indications and acts as a liaison between clinical and technical teams for studies using Signant's electronic clinician ratings platform, Rater Station®.
	Dr. Busner has over 35 years of experience as an academic psychiatric researcher, serving as Principal Investigator for 49 clinical trials and Sub-Investigator for 35 more. She has authored or co-authored over 140 peer-reviewed articles and presentations. Before joining Signant Health, she directed psychiatric clinical trials at two major medical schools and served on University IRBs for 20 years. Currently an Affiliate Associate Professor of Psychiatry at Virginia Commonwealth University, Dr. Busner leads studies at Signant on pediatric, rare, and psychiatric disorders, and has trained thousands of clinical trial investigators worldwide.