The Potential to Leverage Real-World Data for Pediatric Clinical Trials: A Proof-of-Concept Study

Pediatric clinical research, especially in rare diseases, faces persistent challenges including the identification and recruitment of eligible patients, assessing protocol feasibility, and ensuring efficient trial execution. These issues are compounded by small, age-stratified populations and fragmented clinical data. Real-world data (RWD), especially when drawn from electronic health records (EHRs), present an opportunity to support innovative trial designs, such as real-world comparator arms and postmarketing surveillance. However, realizing this potential depends on the routine availability of structured, reusable clinical data.

This proof-of-concept study aimed to assess the availability and structure of routine clinical data in European pediatric hospitals, focusing on data elements relevant for use in comparator arms and postmarketing surveillance studies. The study focused on 2 disease areas-neurofibromatosis (NF) and atopic dermatitis (AD)-as examples of rare and common conditions in children, respectively.

An inventory of 113 high-value clinical data items was developed based on expert analysis of clinical protocols for NF, AD, and safety studies. These items were included in a structured web-based survey disseminated through the connect4children (c4c) National Hub network, reaching sites across. Europe. Respondents were asked to indicate how each data item is collected and stored: in structured/coded EHR fields, as free text, in external systems, or on paper.

Survey responses from 24 hospitals across 11 European countries revealed considerable variability in how data are captured and stored. While many general clinical and drug safety data elements-such as demographics, vital signs, and medication use-were often collected in structured formats, disease-specific and contextual variables were frequently captured as free text or not documented in a standardized way. For example, structured data capture was more prevalent for basic demographic and safety-related variables, whereas only a minority of sites recorded key disease-specific clinical details in a structured form. Lifestyle and family history data were among the least consistently documented. These gaps in structured data entry reduce the immediate reusability of EHR data for secondary research purposes.

This study highlights gaps in the structured documentation of pediatric clinical data across European sites. While the routine collection of many variables is promising, the lack of structured and coded formats poses a barrier to reusing these data for observational studies or comparator arms. As a first step toward the broader integration of RWD into pediatric research, this study demonstrates the feasibility of assessing EHR data availability and sets the stage for future scaling across more diseases and sites.