Development of Conceptual Frameworks and Patient-Reported Outcome Measures in Glycogen Storage Disease Type Ia (GSDIa)


Butler J1, Theodore-Oklota C1, Egan S2, Evans C3
1Ultragenyx Pharmaceutical Inc., Novato, CA, USA, 2Endpoint Outcomes, Long Beach, CA, USA, 3Endpoint Outcomes, Boston, MA, USA

OBJECTIVES: Glycogen Storage Disease Type Ia (GSDIa) is a rare, genetic condition caused by a deficiency of glycose 6-phosphatase, leading to build-ups of glycogen in the body and resulting in hypoglycemia. The objective of this research was to develop disease-specific, PROs for use in patients with GSDIa.

METHODS: Results from an online survey, a targeted literature review, and concept elicitation interviews were used to develop draft conceptual models and questionnaires. Mixed concept elicitation and cognitive interviews were conducted to debrief the draft questionnaires. All interviews were conducted with ethics approval.

RESULTS: The GSD Functional Assessment Diary (FAD) was drafted to collect patient-reported occurrences of symptoms and impacts related to changes in blood sugar. The GSD FAD consists of the GSDIa Morning Diary, designed to assess sleep and cornstarch-related impacts after waking, and the GSDIa Evening Diary, intended to assess the energy-related, neurocognitive, and physical signs and symptoms of hypoglycemia physiology, as well as impacts on daily life. Thirteen hybrid concept elicitation and cognitive interviews were conducted with adolescent (n=4) and adult (n=9) participants to assess the content validity of the GSD FAD. Additionally, three children participated in cognitive interviews to debrief the pediatric version of the measures. Overall, the instructions, items, and response options for the GSD FAD were interpreted as intended and were reported to be clear and relevant. Results were used to update the conceptual models and questionnaires.

CONCLUSIONS: A hybrid, pragmatic approach was taken for the development of the measures that incorporated the flexibility encouraged by the FDA Rare Disease Guidance for Industry balancing the rarity of GSDIa with the rigor of valid PRO development. Preliminary results demonstrate content validity suggesting that the GSD FAD captures the relevant concepts of hypoglycemic signs and symptoms from the patient perspective. Next steps will be to undergo psychometric validation utilizing a similar pragmatic approach.

Conference/Value in Health Info

2022-11, ISPOR Europe 2022, Vienna, Austria

Value in Health, Volume 25, Issue 12S (December 2022)




Methodological & Statistical Research, Patient-Centered Research

Topic Subcategory

Instrument Development, Validation, & Translation, Patient-reported Outcomes & Quality of Life Outcomes, PRO & Related Methods


SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Rare & Orphan Diseases

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