Enhancing rare disease guideline development with real-world data: a method evaluation

Abstract Background Real-world data collection can contribute to quality improvement for rare diseases in several ways. Objectives To evaluate a method developed to integrate real-world evidence in guidelines addressing rare diseases (REGARD). Methods A guideline on omphalocele was developed following the GIN-McMaster Guidelines 2.0 checklist. After the guideline panel selected clinical questions, systematic literature searches were performed. When published evidence was scarce, REGARD was introduced. Data from the European Pediatric Surgical Audit (EPSA) patient registry was provided to clinical experts after which they noted their observations of treatment effect in structured observation forms (SOFs). Feasibility, added value and acceptability of REGARD were evaluated using a cross-sectional study design. Results EPSA data were available for seven of the twelve clinical questions selected for this guideline (58%). In 4/7 clinical questions (57%), REGARD contributed to the panels’ decision on a recommendation. Reasons to disregard the supplementary evidence during the formation of a recommendation were: uncertainty about the validity of the observations due to small sample sizes and doubt about the association between the observed outcomes and the intervention because the registry data lacked information on the clinical indication for a chosen treatment. Conclusions This study evaluates a method to connect real-world data collection to guideline development in rare diseases, highlighting both the challenges and benefits this method has to offer. Although the methodology requires refinement and the EPSA registry must be optimized, we believe it holds significant promise as a tool for developing guidelines for rare diseases.