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Development of the Fibrodysplasia Ossificans Progressiva FLare EXperience Revised (FOP-FLEX-R©) Questionnaire: A
Robert J Pignolo1, Edward C Hsiao2, Mona Al Mukaddam3
1Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Background:
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, genetic disorder mainly characterized by progressive heterotopic ossification (HO). Flare-ups in FOP, involving soft tissue swelling, pain, warmth, and stiffness, often precede HO. We report development of the FOP-FLEX-R© questionnaire (Ipsen, 2026), providing clinical researchers with a comprehensive tool to assess patient experiences during flare-ups, and address the limitations of existing patient-reported outcome measures (PROMs).
Methods:
The FOP-FLEX questionnaire was developed through: a targeted literature review to identify signs, symptoms, and impacts of FOP; concept selection and questionnaire development activities; validation of content and readability in expert consultations and patient interviews; revisions to create the FOP-FLEX-R© questionnaire.
Results:
The literature review identified 42 'sign and symptom' and 28 'impact' concepts. Ten concepts were selected for inclusion in the initial FOP-FLEX: swelling, pain, skin warmth, stiffness, skin redness, impaired daily activities, frustration, bother, fatigue/tiredness, and appetite loss. Consultations with clinical experts (n = 5) and interviews with patients (n = 12) affirmed these concepts. Cognitive debriefing with the same patients indicated the FOP-FLEX was understandable and easy to complete, though some revisions were made, including those to enable the assessment to be completed by younger patients and to remove non-flare-up items.
Conclusions:
The FOP-FLEX-R© questionnaire offers a comprehensive, content-validated PROM for use in clinical trials, to understand the lived experience of flare-ups in FOP and evaluate the benefit of new therapies.
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