OBSERVATIONAL STUDY TO DEVELOP A TREATMENT–RELATED PATIENT-REPORTED OUTCOME MEASURE IN GAUCHER DISEASE (QOL-ONE PRO1G).

Background Gaucher disease (GD) is a rare autosomal recessive lysosomal disorder that results in the accumulation of sphingolipids in the body’s tissues due to glucocerebrosidase enzyme deficiency. GD manifests with vast clinical heterogeneity. Type 1 is the most common form (non neurophatic) with a wide spectrum of signs and symptoms at presentation: some are very mild, others may present variably enlarged liver and spleen which may cause abdominal discomfort. Trombocytopenia and anemia are very common at diagnosis and may be associated with signs and symptoms (bruising and bleeding, tiredness, vertigo, dyspnea and reduced physical functioning). Over 20% of patients experience bone pain or fractures. Treatment is indicated for patients with type 1 GD who exhibit clinical signs and symptoms of the disease, including anemia, thrombocytopenia, skeletal disease, or visceromegaly. Assessment of the impact of illness on physical, mental, and social functioning is an essential element of clinical diagnosis, a major determinant of therapeutic choices and efficacy, and a guide to longer-term care. Furthermore, it is known that patient reported outcomes (PROs) may influence various changes in intervention. There are many generic instruments available to measure the impact of disease on patient’s health-related quality of life (HRQoL). However, there is no PRO measure that has been developed specifically for the use in GD. Such a measure would help clinicians to gain a more in-depth understanding of the impact of GD on patients and inform clinical decision making, leading to better patient care and compliance. Aims The aim of this study is to develop and validate an instrument designed to measure the impact of GD and treatment on individual patients’ PROs. Primary endpoints are the generation of items to construct a PRO instrument for patients with GD and its psychometric evaluation. Methods This is an observational multicentre study. Participants will be GD patients aged ≥ 18 years attending referral centers. The study will be divided in 6 stages: Stage 1 - conceptualisation of PROs in GD patients before the data collection, in order to lay a conceptual foundation for the new instrument; Stage 2 - qualitative interviews; Stage 3 - item generation; Stage 4 - pre-testing; Stage 5 - item reduction; Stage 6 - validation of the final questionnaire. The total number of patients estimated to be assessed is approximately 100. Results The results of first stages of the study will be presented. The issues related to PROs of patients with GD will be researched and conceptualized. The interview guidance on HRQoL and symptom issues related to disease and its treatment will be developed and the interviewer will conduct interviews in accordance with this guidance. Emerging themes on HRQoL and symptoms from the interviews will be reported and are expected to fall into the four main HRQoL domains - physical, social, environmental and psychological. Outcomes of qualitative interviews will be analyzed. Conclusion The user-friendly questionnaire to evaluate impact and symptoms of GD will meet the minimum standards set out by the FDA for PROs and HRQoL instruments that include intrinsic characteristics (reliability and validity), responsiveness, sensitivity to change in health states and adequate sample size (FDA Guidance, 2006; https://www.fda.gov/downloads/drugs/guidances/ucm193282.pdf). The instructions on the questionnaire will be easy to use, and the instrument will be short in length, self-explanatory, take a short time to complete, be easy to use and put minimal burden on the patient.