Abstract
BackgroundDisease-specific patient-reported outcome measures (PROMs) are fundamental to understanding the impact on, and expectations of, patients with genetic disorders, and can facilitate constructive and educated conversations about treatments and outcomes. However, generic PROMs may fail to capture disease-specific concerns. Here we report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruising, bone disease, and fatigue.Results and discussionThe questionnaire was initially developed with input from 85 patients or parents of patients with GD1 or GD3 in Israel. Owing to few participating patients with GD3, content validity was assessed for patients with GD1 only. Content validity of the revised questionnaire was assessed in 33 patients in the US, France, and Israel according to US Food and Drug Administration standards, with input from a panel of six GD experts and one patient advocate representative. Concept elicitation interviews explored patient experience of symptoms and treatments, and a cognitive debriefing exercise explored patients’ understanding and relevance of instructions, items, response scales, and recall period. Two versions of the questionnaire were subsequently developed: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM), and a 17-item version for use in clinical trials (ctGD1-PROM). Psychometric validation of the ctGD1-PROM was assessed in 46 adult patients with GD1 and re-administered two weeks later to examine test–retest reliability. Findings from the psychometric validation study revealed excellent internal consistency and strong evidence of convergent validity of the ctGD1-PROM based on correlations with the 36-item Short Form Health Survey. Most items were found to show moderate, good, or excellent test–retest reliability.ConclusionsDevelopment of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.
Highlights
Gaucher disease (GD) is an autosomal recessive disorder characterized by a deficiency in the lysosomal enzyme acid β-glucosidase (GCase), caused by pathogenic variation in the GBA1 gene [1]
Development of the ctGD1-patient-reported outcome measures (PROMs) represents an important step forward for researchers measuring the impact of GD and its respective treatment
Thousands of patients with GD type 1 (GD1) over the last 25 years have benefited from intravenous treatment with pharmacologic recombinant GCases and more recently from oral, small-molecule inhibitors of glucosylceramide synthase
Summary
Gaucher disease (GD) is an autosomal recessive disorder characterized by a deficiency in the lysosomal enzyme acid β-glucosidase (GCase), caused by pathogenic variation in the GBA1 gene [1]. Thousands of patients with GD1 over the last 25 years have benefited from intravenous treatment with pharmacologic recombinant GCases (enzyme replacement therapy; ERT) and more recently from oral, small-molecule inhibitors of glucosylceramide synthase (substrate reduction therapy). At the more severe end of the phenotypic spectrum, GD2 is characterized by devastating central nervous system and systemic involvement manifesting either at birth or in infancy, and affected infants rarely live for >2–3 years [7, 8]. We report the development and validation of a Gaucher disease (GD)-specific PROM for patients with type 1 Gaucher disease (GD1) a lysosomal storage disorder characterized by hepatosplenomegaly, thrombocytopenia, anemia, bruis‐ ing, bone disease, and fatigue
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
