Qualitative Interviews to Support the Development of a Patient-Reported Outcome (PRO) Measure for Glycogen Storage Disease Type Ia
Clinical Genetics and Therapeutics
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Primary Categories:
- Health services and Implementation
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Secondary Categories:
- Health services and Implementation
Introduction:
No FDA-approved therapy currently exists for glycogen storage disease type Ia (GSDIa). Beam Therapeutics is developing BEAM-301 to treat individuals with GSDIa who are homozygous or compound heterozygous for the G6PC-p.Arg83Cys (p.R83C) variant. BEAM-301 is an in-vivo, liver-targeting lipid nanoparticle formulated investigational therapy designed to correct the p.R83C variant, the most common variant responsible for causing GSDIa. To create a patient-reported outcome (PRO) measure for the BEAM-301 Phase 1/2 clinical trial, we conducted a qualitative interview study to identify key signs, symptoms, and impacts of GSDIa in individuals aged ≥12 years with the p.R83C variant. Participant feedback was used to inform the development of a new measure to assess GSDIa-associated burden of illness in adults and adolescents.
Methods:
A targeted literature review and feedback from expert clinicians and caregivers informed the preliminary identification of concepts for a disease-specific PRO measure. Following IRB approval, participants were recruited via advocacy groups and clinician referral. Qualitative interviews were conducted with 16 participants (10 female, 6 male) via Zoom or telephone across 3 rounds with individuals with self-reported p.R83C variant of GSDIa and currently experiencing symptoms. The age range included 4 adolescents (aged 12-17 years) and 12 adults (aged ≥ 18 years). These hybrid concept elicitation and cognitive debriefing interviews aimed to identify and refine concepts and items related to GSDIa disease burden.
Results:
The 16 participants described a diverse range of GSDIa-related symptoms and impacts. The current standard of care (e.g., glucose/cornstarch supplementation every 3-4 hours) was described as posing a substantial burden. Participants most frequently reported symptoms of fatigue, sweatiness, and hunger. Fatigue, anxiety, and hypoglycemia were reported as the most bothersome symptoms. Participants’ experiences with GSDIa symptoms ranged from mild feelings of irritability, to very severe, which included serious health consequences. Participants emphasized the importance of addressing glucose instability to prevent life-threatening GSDIa impacts. Hypoglycemia was identified as the most crucial symptom to treat, with a unanimous preference for longer-duration treatment effect compared to the current standard of care.
Conclusion:
Due to the heterogeneous nature of the disease, we identified unique symptom concepts through the interviews. This study is the largest qualitative study conducted amongst participants with the p.R83C variant of GSDIa. This diversity observed across participant experiences aligns with findings in the literature, even amongst individuals with the same GSDIa genetic variant and highlights the importance of the development of GSD1a-specific PRO measures. The final preliminary measure assesses 18 symptoms and 24 impacts of GSDIa. Key components of hypoglycemia (e.g., fatigue, sweatiness, shakiness) were fully captured and included in the measure. Based on the totality of evidence gleaned from the literature review and KOL/patient interviews, saturation was attained with respect to the most prevalent and bothersome symptoms. The newly developed PRO measure will be a clinical endpoint in the upcoming BEAM-301 clinical trial.
No FDA-approved therapy currently exists for glycogen storage disease type Ia (GSDIa). Beam Therapeutics is developing BEAM-301 to treat individuals with GSDIa who are homozygous or compound heterozygous for the G6PC-p.Arg83Cys (p.R83C) variant. BEAM-301 is an in-vivo, liver-targeting lipid nanoparticle formulated investigational therapy designed to correct the p.R83C variant, the most common variant responsible for causing GSDIa. To create a patient-reported outcome (PRO) measure for the BEAM-301 Phase 1/2 clinical trial, we conducted a qualitative interview study to identify key signs, symptoms, and impacts of GSDIa in individuals aged ≥12 years with the p.R83C variant. Participant feedback was used to inform the development of a new measure to assess GSDIa-associated burden of illness in adults and adolescents.
Methods:
A targeted literature review and feedback from expert clinicians and caregivers informed the preliminary identification of concepts for a disease-specific PRO measure. Following IRB approval, participants were recruited via advocacy groups and clinician referral. Qualitative interviews were conducted with 16 participants (10 female, 6 male) via Zoom or telephone across 3 rounds with individuals with self-reported p.R83C variant of GSDIa and currently experiencing symptoms. The age range included 4 adolescents (aged 12-17 years) and 12 adults (aged ≥ 18 years). These hybrid concept elicitation and cognitive debriefing interviews aimed to identify and refine concepts and items related to GSDIa disease burden.
Results:
The 16 participants described a diverse range of GSDIa-related symptoms and impacts. The current standard of care (e.g., glucose/cornstarch supplementation every 3-4 hours) was described as posing a substantial burden. Participants most frequently reported symptoms of fatigue, sweatiness, and hunger. Fatigue, anxiety, and hypoglycemia were reported as the most bothersome symptoms. Participants’ experiences with GSDIa symptoms ranged from mild feelings of irritability, to very severe, which included serious health consequences. Participants emphasized the importance of addressing glucose instability to prevent life-threatening GSDIa impacts. Hypoglycemia was identified as the most crucial symptom to treat, with a unanimous preference for longer-duration treatment effect compared to the current standard of care.
Conclusion:
Due to the heterogeneous nature of the disease, we identified unique symptom concepts through the interviews. This study is the largest qualitative study conducted amongst participants with the p.R83C variant of GSDIa. This diversity observed across participant experiences aligns with findings in the literature, even amongst individuals with the same GSDIa genetic variant and highlights the importance of the development of GSD1a-specific PRO measures. The final preliminary measure assesses 18 symptoms and 24 impacts of GSDIa. Key components of hypoglycemia (e.g., fatigue, sweatiness, shakiness) were fully captured and included in the measure. Based on the totality of evidence gleaned from the literature review and KOL/patient interviews, saturation was attained with respect to the most prevalent and bothersome symptoms. The newly developed PRO measure will be a clinical endpoint in the upcoming BEAM-301 clinical trial.
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