Development and Preliminary Psychometric Evaluation of the Glycogen Storage Disease Type Ia Functional Assessment...

Glycogen storage disease type Ia (GSDIa) is a rare, inherited, autosomal recessive condition with deficiency of glucose-6-phosphatase (G6Pase) characterized by fasting hypoglycemia due to an inability to release glucose from hepatic glycogen stores and other metabolic pathways, requiring frequent consumption of exogenous glucose for survival. Patient-reported outcome (PRO) measures are important to assess GSDIa burden, though no disease-specific PRO for GSDIa exists. This research describes the Glycogen Storage Disease Functional Assessment Diary (GSD FAD), a 31-item PRO developed to assess the signs/symptoms and impacts of GSDIa in individuals ages 8 and older.

Mixed methods research including a literature review, online survey, and concept elicitation (CE) interviews informed the construction of the GSD FAD. Cognitive debriefing (CD) interviews evaluated concept relevance and understanding of the questionnaire. Psychometric properties were evaluated using Phase 3 trial screening/baseline data to assess item variability, structure/scaling potential, scoring, reliability, validity, and minimum detectable change.

The literature review, online survey (N=26), and CE interviews (N=7) identified hypoglycemia and cornstarch regimen impacts as most burdensome and most important to treat from the patient perspective. The initial draft GSD FAD included 36 items. Most items were interpreted as intended in CD interviews (N=16); revisions to the GSD FAD addressed interpretation issues. Three domain scores (Symptoms Total Score, Sleep Impacts Total Score, and Daily Impacts Total Score) showed acceptable reliability and validity but had notable ceiling effects that may limit responsiveness in some settings.

The GSD FAD is a novel, content-valid PRO that measures the humanistic burden of GSDIa and cornstarch treatment regimen, including the signs/symptoms of hypoglycemia and their impact on health-related quality of life (HRQoL) in individuals ≥ 8 years with GSDIa, that yields reliable and valid scores. While developed in a trial setting, the GSD FAD has potential for use in nutritional, behavioral, and/or educational applications.