STRUCTURING VALUE ELEMENTS FOR COST-EFFECTIVENESS MODELING: THE STEPPS FRAMEWORK APPLIED TO FAZIRSIRAN IN ALPHA-1 ANTITRYPSIN DEFICIENCY-ASSOCIATED LIVER DISEASE
Author(s)
Andrew Briggs, DPhil1, Michael John Lacey, MSc2, Amy Duhig, PhD3, Chitra Karki, MPH4, Tami Nussbaum, MD5, Kayla Klein, PhD5, Evi Germeni, PhD6.
1Professor of Health Economics, London School of Hygiene & Tropical Medicine, London, United Kingdom, 2Takeda Pharmaceuticals, Cambridge, MA, USA, 3Takeda Development Centre, Cambridge, MA, USA, 4Takeda Pharmaceuticals, Winchester, MA, USA, 5Takeda Development Centre Americas, Inc, Cambridge, MA, USA, 6University of Glasgow, Glasgow, United Kingdom.
1Professor of Health Economics, London School of Hygiene & Tropical Medicine, London, United Kingdom, 2Takeda Pharmaceuticals, Cambridge, MA, USA, 3Takeda Development Centre, Cambridge, MA, USA, 4Takeda Pharmaceuticals, Winchester, MA, USA, 5Takeda Development Centre Americas, Inc, Cambridge, MA, USA, 6University of Glasgow, Glasgow, United Kingdom.
OBJECTIVES: Value frameworks for health economic analysis have suggested additional value elements to the standard cost-effectiveness approach without offering a structure for deciding which to include in a model, which to address outside the model, and which fall outside conventional modelling altogether. This challenge is critical in rare genetic diseases, where diagnostic burden, uncertainty, stigma, caregiver impacts, and the value of hope may be important but difficult to represent consistently.
METHODS: Drawing on a prior stakeholder-derived inventory of 103 value elements for fazirsiran, an investigational therapy for alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD), we propose three connected conceptual contributions.
RESULTS: First, the STEPPS framework - six dimensions covering Stages of disease, Treatment options, Endpoints and outcomes, Patients and caregivers, Payors, and Stratification variables. Unlike conventional value-element taxonomies, STEPPS directly links organising value and specifying model architecture. Second, a three-state conceptual model - silent, known, and treatable disease - each containing a common progression chain (fibrosis → cirrhosis → decompensated cirrhosis or hepatocellular carcinoma → transplant → death). This makes explicit something usually hidden: that diagnosing a debilitating genetic condition for which no effective treatment exists is itself value-relevant, plausibly reducing quality of life. An effective treatment then has dual value - improving prognosis and mitigating the anxiety induced by diagnosis. Third, the recognition that some elements - disease stigma, value of hope, scientific spillovers, severity modifiers, transplant-community externalities - sit outside conventional modelling scope and are best handled as deliberative decision factors or through targeted framework extension. Of these, stigma and hope appear particularly material in a rare progressive disease like AATD-LD.
CONCLUSIONS: Together, these constructs separate value elements that can be modelled from those better addressed through deliberation or framework extension, directing methodological attention to the elements that matter most. They also provide a transparent basis for incorporating patient experience into value assessment.
METHODS: Drawing on a prior stakeholder-derived inventory of 103 value elements for fazirsiran, an investigational therapy for alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD), we propose three connected conceptual contributions.
RESULTS: First, the STEPPS framework - six dimensions covering Stages of disease, Treatment options, Endpoints and outcomes, Patients and caregivers, Payors, and Stratification variables. Unlike conventional value-element taxonomies, STEPPS directly links organising value and specifying model architecture. Second, a three-state conceptual model - silent, known, and treatable disease - each containing a common progression chain (fibrosis → cirrhosis → decompensated cirrhosis or hepatocellular carcinoma → transplant → death). This makes explicit something usually hidden: that diagnosing a debilitating genetic condition for which no effective treatment exists is itself value-relevant, plausibly reducing quality of life. An effective treatment then has dual value - improving prognosis and mitigating the anxiety induced by diagnosis. Third, the recognition that some elements - disease stigma, value of hope, scientific spillovers, severity modifiers, transplant-community externalities - sit outside conventional modelling scope and are best handled as deliberative decision factors or through targeted framework extension. Of these, stigma and hope appear particularly material in a rare progressive disease like AATD-LD.
CONCLUSIONS: Together, these constructs separate value elements that can be modelled from those better addressed through deliberation or framework extension, directing methodological attention to the elements that matter most. They also provide a transparent basis for incorporating patient experience into value assessment.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
MSR152
Topic
Economic Evaluation, Medical Technologies, Methodological & Statistical Research
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Rare & Orphan Diseases