DEVELOPMENT OF A COMPOSITE ENDPOINT IN HYPOPHOSPHATASIA TO OPTIMIZE COST-EFFECTIVENESS DEMONSTRATION
Author(s)
Philippe Laramee, PhD1, Zorana Zupan, PhD1, Damien Simoneau, PhD2, Craig Wakeford, PhD3, Nicolas Voirin, PhD4, Aline Gauthier, MSc5, Laurent Boyer, PhD6;
1Alexion Pharma, Barcelona, Spain, 2Alexion Pharma, Baar, Switzerland, 3Alexion Pharma, Boston, MA, USA, 4Amaris, Lyon, France, 5Amaris, Barcelona, Spain, 6Aix-Marseille Université, Marseille, France
1Alexion Pharma, Barcelona, Spain, 2Alexion Pharma, Baar, Switzerland, 3Alexion Pharma, Boston, MA, USA, 4Amaris, Lyon, France, 5Amaris, Barcelona, Spain, 6Aix-Marseille Université, Marseille, France
OBJECTIVES: Hypophosphatasia in adults presents with burden across mobility, physical function, pain, fatigue, and broader health-related quality of life. However, no existing clinical outcome assessment captures the multidimensional nature of this burden. To better capture treatment effects, we propose a composite endpoint combining patient-reported and performance outcomes, based on existing assessments and suited for cost-effectiveness modelling.
METHODS: The composite endpoint will combine data from the 6-Minute Walk Test (mobility/endurance), Sit-to-Stand (mobility/strength), Lower Extremity Functional Scale (physical/daily functioning), Brief Pain Inventory-Short Form (pain), FACIT-F (fatigue), and SF-36 domains (physical, emotional, and social functioning). Score distributions will be assessed to remove redundancies, then rescaled to a common metric. Weights will be derived empirically from trial data and informed by literature and qualitative interviews with clinicians and patient representatives, to reflect relative importance from patient and clinical perspectives. Robustness will be assessed through sensitivity and uncertainty analyses. The continuous composite endpoint will be mapped to discrete health states using meaningful within-patient change thresholds.
RESULTS: We expect the composite endpoint to be more sensitive to change than any individual endpoint. By integrating multiple clinically relevant measures into a single outcome, it may capture multidimensional improvements not consistently detected by individual endpoints. This increased responsiveness should enable more precise estimation of treatment effects and supports more robust comparisons between interventions.
CONCLUSIONS: A rigorous, patient-centered composite endpoint for hypophosphatasia can consolidate multidimensional outcomes into a single, interpretable measure. This approach enables health-state categorization for economic evaluation and strengthens cost-effectiveness modelling to inform value assessments and reimbursement decisions.
METHODS: The composite endpoint will combine data from the 6-Minute Walk Test (mobility/endurance), Sit-to-Stand (mobility/strength), Lower Extremity Functional Scale (physical/daily functioning), Brief Pain Inventory-Short Form (pain), FACIT-F (fatigue), and SF-36 domains (physical, emotional, and social functioning). Score distributions will be assessed to remove redundancies, then rescaled to a common metric. Weights will be derived empirically from trial data and informed by literature and qualitative interviews with clinicians and patient representatives, to reflect relative importance from patient and clinical perspectives. Robustness will be assessed through sensitivity and uncertainty analyses. The continuous composite endpoint will be mapped to discrete health states using meaningful within-patient change thresholds.
RESULTS: We expect the composite endpoint to be more sensitive to change than any individual endpoint. By integrating multiple clinically relevant measures into a single outcome, it may capture multidimensional improvements not consistently detected by individual endpoints. This increased responsiveness should enable more precise estimation of treatment effects and supports more robust comparisons between interventions.
CONCLUSIONS: A rigorous, patient-centered composite endpoint for hypophosphatasia can consolidate multidimensional outcomes into a single, interpretable measure. This approach enables health-state categorization for economic evaluation and strengthens cost-effectiveness modelling to inform value assessments and reimbursement decisions.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO112
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Clinician Reported Outcomes, Comparative Effectiveness or Efficacy, Performance-based Outcomes
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Rare & Orphan Diseases