Development of a single item patient reported measure of treatment side effect burden in clinical trials of rheumatic and musculoskeletal diseases using stakeholder input and large language model refinement

Objectives
To build on existing evidence regarding single-item measurement instruments of patient-reported bother or trouble from medical side effects in individuals with rheumatic and musculoskeletal diseases (RMDs). Further, to collect input from the OMERACT community through a structured survey that rated and ranked available options and to seek agreement to advance one or more of these measures for use as exploratory outcomes in future clinical trials.

Methods
At OMERACT 2025 we presented and discussed survey results for domain match, feasibility and ranking of six candidate instruments of bother or trouble from side effects. Collaborator feedback - including comments from patients, clinicians, and researchers - was synthesized with a large-language-model (LLM) to identify key concerns and guide refinement of the instrument’s relevance, clarity, and acceptability. The LLM- assisted synthesis of participant comments resulted in a new, single-item instrument designed to improve patient safety reporting from the patient’s perspective.

Results
The merged and modified version of the instrument was presented at the OMERACT 2025 meeting, where 33 participants approved it as a reasonable approach to incorporate collaborator input. The proposed instrument is feasible (32 [97%]) and voting supported advancing its further assessment (30 [91%]) as an exploratory outcome measurement instrument in coming RMD trials.

Conclusions
We developed a novel single-item instrument. This is the first known application of LLMs in refining a patient-reported outcome instrument for clinical trials. It is designed to capture the patient perspective on symptomatic treatment-related side effects in RMDs and is supported for exploratory use in trials.

Aim

To build on existing evidence regarding single-item measurement instruments of patient-reported bother or trouble from medical side effects in individuals with RMDs. Further, to collect input from the OMERACT community through a structured survey that rated and ranked available options and to seek agreement to advance one or more of these measures for use as exploratory outcomes in future clinical trials.

Contributors

Dorthe B. Berthelsen, Ben Horgan, Lee Simon, John P.A. Ioannidis, Niti Goel, Peter Tugwell, Erin Balay-Dustrude, Susan J. Bartlett, Clifton O. Bingham, Maarten Boers, Coralie Bouillot, Peter Böhm, Ernest Choy, Mary Cowern, Krista Dagsvik, Chris Djurtoft, Daniel E. Furst, Tobias Haugegaard, Glen S. Hazlewood, Alison M. Hoens, Tanja Schjødt Jørgensen, Shannon E. Kelly, Denise Kruzikas, Joachim Musaus, Pam Richards, Beverly J. Shea, Vibeke Strand, Megan Thomas, Karina Torralba, Marieke Voshaar, Max Weinbrecht-Mischkewitz, Thasia G. Woodworth, Grace Wright, Caroline Flurey, Robin Christensen, on behalf of the OMERACT Safety Working Group

Publication

Journal: Semin Arthritis Rheum.
Volume: 79
Issue: 153026
Pages: -
Year: 2026
DOI: 10.1016/j.semarthrit.2026.153026.

Further Study Information

Current Stage: Completed
Date:
Funding source(s): Section for Biostatistics and Evidence-Based Research, the Parker Institute is supported by a core grant from the Oak Foundation (OFIL- 24–074). The Oak Foundation is a group of philanthropic organizations and, since its establishment in 1983; it has given grants to not-for-profit organizations around the world. TH has received a travel grant from the Patient Association at the Parker Institute. The Oak Foundation and Patient Association had no role in the study design, data collection and analyses, interpretation or reporting of this work, or the decision to submit the work for publication. DBB has received PhD Scholarships from Odense University Hospital and from the Faculty of Health Sciences, University of Southern Denmark.

---

Method(s)

- Consensus meeting

Linked Studies

No related studies

Related Links

No related links