OBJECTIVES: Advanced forms of systematic mastocytosis (advSM) are rare diseases characterized by neoplastic mast cell infiltration of tissues, resulting in a variety of disease-related signs and symptoms. Informed by results from the literature, expert advice meetings, and patient concept elicitation interviews, the advSM Symptom Assessment Form (advSM-SAF) was developed to evaluate treatment efficacy in regulated clinical trials. Before implementation in clinical studies, the advSM-SAF was subject to cognitive debriefing interviews (CDIs) to understand and document the extent to which the tool was understandable to patients with advSM and the extent to which they could provide meaningful responses to the questionnaire. METHODS: The advSM-SAF is a 10-item electronic diary assessing eight advSM symptoms using a 24-hour recall period and a 0-10 numeric response scale. CDIs were conducted with patients with advSM to evaluate the advSM-SAF for readability, relevance, and comprehensiveness, and to test the usability of the electronic patient-reported outcome (ePRO) device. Subjects were asked to complete the advSM-SAF and provide feedback on the instructions, items, and response options. RESULTS: CDIs were conducted with 13 subjects with advSM. At least 78%, 89%, and 92% of subjects interpreted each of the response options, instructions, and items, respectively, as intended by the instrument developers. Based on subject feedback, one text deletion and one revision, a reordering of items on sign/symptom severity to follow those on sign/symptom frequency, were made to the advSM-SAF. Subjects reported no issues with ePRO device usability. CONCLUSIONS: The CDI results indicate that the advSM-SAF is understandable to patients with advSM and that it can provide scores that accurately reflect their health status. These results, along with those from previously collected information from the literature, therapeutic area experts, and patients provide support for the ADVSM-SAF as a content valid questionnaire ready for implementation into clinical trial settings.