Development and validation of the idiopathic multicentric Castleman disease symptom burden scale (ISBUS): Protocol for an international multistage mixed methods study

Background:

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder that is associated with a broad range of symptoms, including constitutional, gastrointestinal, neuropsychiatric, dermatologic, respiratory, and hematologic or lymphoreticular problems. These broad symptoms can impact the daily lives of people living with iMCD, creating a high symptom burden. Despite this, no robust, disease-specific patient-reported outcome measure (PROM) for subjective iMCD symptom burden exists. This limits accurate symptom monitoring, impacts sensitive end point selection in clinical trials, and represents a regulatory gap in patient-centered evidence generation when evaluating iMCD treatments.

Objective:

This protocol describes the international multistakeholder Idiopathic Multicentric Castleman Disease Symptom Burden Scale (ISBUS) project. The primary aim of this project is to develop and preliminarily evaluate the measurement properties of a novel PROM for capturing symptom burden (ie, perceived symptom frequency and impact on daily life) in people living with iMCD. The central objective is to produce a valid and robust PROM that can be used to assess iMCD symptom burden in research, clinical trials, and symptom monitoring in clinical practice.

Methods:

The project has a mixed methods design, split into 4 sequential stages, with collaborative advisory input throughout. Stage 1 uses existing data and consultation with expert clinical and patient advisors to generate draft PROM content. Stage 2 uses qualitative cognitive debriefing interviews (n=10) to evaluate the content validity of the draft PROM content and enable meaningful revisions. Stage 3 involves a cross-sectional quantitative survey design in people living with iMCD (n≥50), allowing for psychometric analyses of structural validity (using classical test theory and/or Rasch methodology), construct validity (known-group validity and correlational methods), and internal consistency reliability (Cronbach α). Stage 4 uses a mixed methods design, including longitudinal quantitative survey evidence (n≥20) and qualitative interviews (n=10), triangulated to estimate preliminary meaningful change estimates for the new PROM. The project is international in scope, with primary data collection in 6 countries (ie, Australia, Brazil, Canada, New Zealand, the United Kingdom, and the United States).

Results:

Funding for ISBUS began in June 2023 and is ongoing. As of March 2026, stage 3 had been completed, with 51 people living with iMCD completing the survey, and stage 4 was ongoing, with 32 follow-up surveys completed. Analyses for stages 1-3 were completed and are expected to be published in 2026, followed by stage 4 findings in 2027.

Conclusions:

The aim of the ISBUS project is to produce a novel symptom burden PROM codeveloped with patients with iMCD to measure what matters to patients with iMCD. It is anticipated that the new PROM will be used in iMCD research, as a secondary end point in trials, and as a clinical tool to monitor symptom burden in the management of iMCD.

Trial Registration:

ClinicalTrials.gov NCT05995834; https://clinicaltrials.gov/study/NCT05995834

International Registered Report Identifier (IRRID):

DERR1-10.2196/96022