Prioritizing topics for a clinical practice guideline on SATB2-associated syndrome: methodological rigor vs clinical usability

OBJECTIVES: SATB2-associated syndrome (SAS) is a rare genetic condition characterized by developmental delay and typical features. Currently, an evidence-based clinical practice guideline (CPG) is being developed by European Reference Network ITHACA in close collaboration with the patient community. To ensure that the guideline addresses the most pressing concerns of affected individuals, families, and clinicians, while remaining feasible to produce, a prioritization process was carried out. STUDY DESIGN AND SETTING: The prioritization process aimed to minimize the relevant clinical questions to a maximum of 12, based on criteria that were defined beforehand and based on input from a large patient community. The prioritization process included a SAS community-wide survey that collected all patient-relevant topics, a prioritization round using a tool that helps to calculate the items that were most voted on, and a final consensus round with the guideline core group. RESULTS: In the first round, a total of 376 topics was collected based on input from over 20 families. These were combined and refined into 48 clinical topics. A total of 269 valid responders filled in their prioritization on these topics in an online survey. Of these respondents, 234 identified as representative/family/carer, 30 identified as clinician, and 5 individuals identified as both. Rather than prioritizing a subset of 12 topics, that each would be answered with a systematic review, the core group decided on a final set of 22 questions and only 1 systematic review. CONCLUSION: Despite using a rigorous, community-driven process with input from many parents, carers, and global clinical experts, the guideline core group could not agree on a final set of 12 clinical topics. The group concluded that completeness and clinical usability of the guideline should take precedence over adhering to 12 prioritized clinical topics that could each be answered with a systematic search in the literature. We concluded that completeness and usability, vs methodological rigor, are competing interests in CPG development. This methodological issue is a pressing matter in the field of rare disease CPG development, and possibly also beyond the context of rare diseases, for which no clear solution currently exists. PLAIN LANGUAGE SUMMARY: SATB2-associated syndrome (SAS) is a rare genetic condition that causes developmental delays and other characteristic features. A new clinical practice guideline (CPG) for SAS is currently being developed by the European Reference Network ITHACA, together with families, caregivers, and health-care professionals. To make sure the guideline focuses on the most important needs of the SAS community, a structured process was used to decide which clinical topics should be included. First, families across the SAS community were asked to share their concerns. This resulted in 376 topics, which were combined into 48 broader clinical themes. Next, 269 people completed an online survey to rank these topics. Most respondents were family members or caregivers, and some were clinicians. Finally, the guideline development team reviewed the results and discussed which topics should be prioritized. Although the original goal was to select 12 questions to answer through systematic reviews, the team decided that limiting the guideline to only 12 topics would leave out important issues. Instead, they agreed on 22 key questions, which would be addressed with only 1 systematic review. The CPG recommendations would then be more complete but supported with less systematically searched evidence. This experience highlights an ongoing challenge in rare disease guideline development: balancing completeness and practicality with strict methodological standards.