Development of a Conceptual Model Supporting a Clinical Outcome Assessment Strategy for Acquired Angioedema Due to C1 Inhibitor Deficiency
Author(s)
Marc A. Riedl, MD1, Danny M. Cohn, MD PhD2, Delphine Gobert, MD3, Andrea Zanichelli, MD4, Sarah Clifford, MSc, PhD5, Beverly Romero, MA5, Kelsie Brewer, MEd5, Swaha Pattanaik, MA DrPH5, Maggie Chen, PhD6, Joan Mendivil, MSc, MD7.
1University of California San Diego, Division of Allergy and Immunology, La Jolla, CA, USA, 2Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands, 3Sorbonne Université, Médecine Interne, AP-HP, Centre de référence des angioedèmes à kinines, Hôpital Saint-Antoine, Paris, France, 4Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute; I.R.C.C.S., Policlinico San Donato, Centro Angioedema, UO Medicina, Milan, Italy, 5Sprout Health Solutions, Los Angeles, CA, USA, 6Pharvaris Inc., Lexington, MA, USA, 7Pharvaris GmbH, Zug, Switzerland.
1University of California San Diego, Division of Allergy and Immunology, La Jolla, CA, USA, 2Amsterdam UMC, University of Amsterdam, Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands, 3Sorbonne Université, Médecine Interne, AP-HP, Centre de référence des angioedèmes à kinines, Hôpital Saint-Antoine, Paris, France, 4Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute; I.R.C.C.S., Policlinico San Donato, Centro Angioedema, UO Medicina, Milan, Italy, 5Sprout Health Solutions, Los Angeles, CA, USA, 6Pharvaris Inc., Lexington, MA, USA, 7Pharvaris GmbH, Zug, Switzerland.
Presentation Documents
OBJECTIVES: Acquired angioedema due to C1 inhibitor deficiency (AAE-C1INH) is a rare disease mediated by bradykinin and characterized by unpredictable, painful swelling attacks. There are no approved therapies for AAE-C1INH attacks and no patient-reported outcome (PRO) tools validated for use in clinical investigations. To address this knowledge gap and ensure regulator-required patient input, we aimed to develop a conceptual model of AAE-C1INH that could reveal important disease concepts supporting a clinical outcome assessment strategy. Here, the design of a combined concept elicitation and cognitive interview study assessing the real-world patient experience with AAE-C1INH is reported.
METHODS: Target enrollment is 10 US participants with AAE-C1INH. Concept elicitation aimed to reveal patients’ daily life experiences with AAE-C1INH. Cognitive interviews aimed to explore and confirm the relevance of adapting PRO items validated for hereditary angioedema (HAE), another bradykinin-mediated disease with similar manifestations, for AAE-C1INH. The Patient Global Impression of Change (PGI-C) and Severity (PGI-S) items previously validated for assessing on-demand treatment of HAE attacks were adapted for AAE-C1INH and discussed with patients in remote interviews designed to assess patients’ perceptions of the clarity, interpretation, and meaningful levels of change on the PGI-C and PGI-S. A semi-structured interview guide, including open-ended questions to elicit patients’ descriptions of AAE-C1INH manifestations and impact and structured questions to assess the understanding and relevance of the PGI items, were used. Data will be analyzed using a mixed thematic and content analysis approach.
RESULTS: Recruitment began after IRB approval in November 2024. Six interviews have been completed. The final consolidated results will enable the development of the conceptual disease model.
CONCLUSIONS: The results of this qualitative interview study will inform the creation of a conceptual disease model for AAE-C1INH and may confirm the relevance and appropriateness of selected PROs, including PGI-C and PGI-S, for use in clinical trials of investigational treatments for AAE-C1INH.
METHODS: Target enrollment is 10 US participants with AAE-C1INH. Concept elicitation aimed to reveal patients’ daily life experiences with AAE-C1INH. Cognitive interviews aimed to explore and confirm the relevance of adapting PRO items validated for hereditary angioedema (HAE), another bradykinin-mediated disease with similar manifestations, for AAE-C1INH. The Patient Global Impression of Change (PGI-C) and Severity (PGI-S) items previously validated for assessing on-demand treatment of HAE attacks were adapted for AAE-C1INH and discussed with patients in remote interviews designed to assess patients’ perceptions of the clarity, interpretation, and meaningful levels of change on the PGI-C and PGI-S. A semi-structured interview guide, including open-ended questions to elicit patients’ descriptions of AAE-C1INH manifestations and impact and structured questions to assess the understanding and relevance of the PGI items, were used. Data will be analyzed using a mixed thematic and content analysis approach.
RESULTS: Recruitment began after IRB approval in November 2024. Six interviews have been completed. The final consolidated results will enable the development of the conceptual disease model.
CONCLUSIONS: The results of this qualitative interview study will inform the creation of a conceptual disease model for AAE-C1INH and may confirm the relevance and appropriateness of selected PROs, including PGI-C and PGI-S, for use in clinical trials of investigational treatments for AAE-C1INH.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR238
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Rare & Orphan Diseases