Conducting multicenter randomized controlled trials (RCTs) in pediatric surgery for rare congenital anomalies presents unique challenges, including low patient recruitment, complex regulatory landscapes, and variability in care standards. This paper reflects on the experiences and lessons learned from the MUC-FIRE and STEPS-EA trials, supported by the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA), to provide guidance for future studies.

A retrospective review was conducted on the design and execution of these trials, focusing on team composition, endpoint selection, patient recruitment strategies, regulatory compliance, and adaptive methodologies. Insights were derived from study protocols, monitoring reports, and the authors' experiences.

Key factors contributing to trial success included multidisciplinary collaboration, leveraging existing research networks, and defining clear, measurable endpoints. Challenges such as recruitment delays, regulatory hurdles, and variations in care were mitigated through flexible protocols, proactive amendments, and stakeholder engagement. The COVID-19 pandemic amplified these difficulties, necessitating innovative strategies and extended timelines.

The MUC-FIRE and STEPS-EA trials underscore the critical importance of international collaboration, adaptive strategies, and patient-centered approaches in overcoming the complexities of multicenter RCTs. Lessons from these experiences can inform the design and implementation of future trials, ultimately enhancing evidence generation and improving outcomes for children with rare congenital anomalies.

*Joint first authors and contributed equally to this work.

**Joint last authors and contributed equally to this work.

Received: 13 February 2025

Accepted: 28 April 2025

Article published online:
21 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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