Development and Validation of Gaucher Disease Type 1 (GD1)-Specific Patient-Reported Outcome Measures (PROMs) for Clinical Monitoring and for Clinical Trials

Orphanet J Rare Dis. 2022 Jan 6;17(1):9. doi: 10.1186/s13023-021-02163-y.

PMID: 34991656

Deborah Elstein, Nadia Belmatoug, Patrick Deegan

Highlights: Development of the ctGD1-PROM represents an important step forward for researchers measuring the impact of GD and its respective treatment.

Abstract

Background: Disease-specific PROMs (patient-reported outcome measures) are essential for understanding the impact on, and expectations of, patients with genetic disorders, and can help to allow constructive and informed discussions regarding treatments and outcomes. Generic PROMs, on the other hand, may miss disease-specific problems. The creation 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 damage, and fatigue, is described in this paper.

Results and Discussion: The questionnaire was created with the help of 85 patients or parents of GD1 or GD3 patients in Israel. Because there were so few patients with GD3 who participated, content validity was solely examined for those with GD1. With advice from a panel of six GD experts and one patient advocate representative, the content validity of the redesigned questionnaire was examined in 33 patients in the United States, France, and Israel, according to US Food and Drug Administration standards. 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. Following that, two versions of the questionnaire were created: a 24-item version for routine monitoring in clinical practice (rmGD1-PROM) and a 17-item version for clinical trials (rmGD1-PROM) (ctGD1-PROM). The ctGD1-PROM was tested for psychometric validity in 46 adult patients with GD1 and then re-administered two weeks later to determine test-retest reliability. Based on correlations with the 36-item Short Form Health Survey, the psychometric validation study indicated excellent internal consistency and substantial evidence of convergent validity of the ctGD1-PROM. The majority of the items had moderate, good, or exceptional test-retest reliability.

Conclusions: The creation of the ctGD1-PROM is a significant step forward for researchers attempting to quantify the impact of GD and its treatment.

Keywords: Content validation, Gaucher disease, Lysosomal storage disorder, PROM, Patient-reported outcomes, Psychometric validation, Questionnaire