Expertise of European Clinical Trial Units in Conducting and Managing Cross-Border Pediatric Clinical Trials for Rare Diseases

INTRODUCTION: Conducting pediatric clinical trials across borders in Europe presents unique challenges, especially when studies target rare conditions, require specialized expertise at participating sites, and demand active family involvement in the research process. Including international patients in clinical trials is essential for both scientific development and equity in healthcare, but it requires adapting study protocols, informed consent processes, and patient-reported outcome measures (PROMs) to ensure trial feasibility in diverse linguistic and cultural contexts. The current regulatory and legislative frameworks offer limited solutions to address the language barriers and logistical complexities that still limit cross-border access to clinical trials. The aim of this study was to investigate the experience, expertise, and practices of managing international participants in the pediatric clinical trials conducted by clinical trial units (CTUs) in 17 European countries. METHODS: To assess experiences with cross-border pediatric clinical trials for rare diseases across multiple domains, three online surveys were developed and disseminated to Clinical Trial Units (CTUs) within healthcare organizations across Europe. The first survey captured information on general expertise, the second focused on reported good practices in trials involving international patients, and the third aimed to identify documented cases of discrimination, particularly those related to native language requirements. All surveys were reviewed by an expert advisory board and distributed through multiple European research networks and other channels. Data were analyzed using descriptive statistics and thematic analysis. RESULTS: A total of 43 CTUs from 17 European countries participated in this study, representing a mix of children's hospitals, general hospitals, and university hospitals. International patients who travelled to the 43 CTUs to participate in clinical trials came from 81 different European and non-European countries, mostly from Morocco, Ukraine, Ecuador, and Venezuela. Among the reported good practices supporting cross-border access (N = 113), the most common involved providing written and verbal translations of informed consent documents, patient-reported outcome measures (PROMs), and quality of life (QoL) scales when these were not available in patients' native languages. Twenty cases of discrimination were reported, primarily due to language requirements included in eligibility criteria, which negatively affected trial access for non-native speakers. Most of these cases occurred in industry-sponsored trials for rare diseases (65%, n = 13), which imposed significant logistical burdens, including frequent visits and overnight stays at the hospitals conducting the trial. CONCLUSIONS: While some progress has been made in enabling cross-border access to pediatric clinical trials in Europe, substantial barriers remain, particularly regarding native language diversity and support services for international patients and their families. Systemic changes are needed, including routine translations of study materials, professional interpretation, adaptation of PROMs, and the establishment of dedicated support structures. Collaboration across Europe will be necessary to harmonize language requirements when scientifically justified in the eligibility criteria, promote decentralized trial models, and ensure equitable access to clinical trials for all children, regardless of native language or nationality.