SPIRIT-Children and Adolescents (SPIRIT-C) 2026 extension statement: enhancing the reporting and usefulness of paediatric randomised trial protocols

The SPIRIT-Children and Adolescents (SPIRIT-C) Extension provides a structured framework to support the development and reporting of paediatric randomised clinical trial protocols. It extends the SPIRIT recommendations by introducing additional protocol items specifically relevant to children and adolescents, recognising that paediatric trials require considerations beyond those applied in adult populations.

The guidance supports investigators in designing comprehensive and transparent protocols by addressing paediatric-specific aspects such as developmental appropriateness of interventions, age-related dose considerations, selection of relevant outcomes, safety monitoring approaches, participant and family involvement, and strategies to minimise burden and distress for children participating in research.

This resource is particularly valuable for rare disease clinical trials because many rare diseases have paediatric onset and require research approaches adapted to very small, heterogeneous and vulnerable populations. In these settings, protocol quality is critical because recruitment opportunities are limited, trial modifications may be difficult once initiated, and each participant contributes substantial scientific value. SPIRIT-C can help investigators ensure that essential methodological and ethical considerations are incorporated from the earliest stages of trial planning.

The tool is especially relevant for rare disease trials involving children and adolescents because it supports better alignment between scientific objectives, participant needs and feasibility constraints. By encouraging appropriate outcome selection, transparent safety planning and meaningful involvement of young people and families, it can contribute to more relevant, acceptable and successful paediatric clinical trials.

Although developed for paediatric randomised trials in general, SPIRIT-C is highly applicable to paediatric rare disease research and complements other rare disease-specific resources addressing small population trial design, outcome selection, patient engagement and regulatory strategy.