ARDVARC- Advancing Rare Disorders: Vascular mAlformations Research Network with CaNVAS: PROMS Measures

ARDVARC Project 2: Project Summary/Abstract Vascular malformations (VMs) result from abnormal overgrowth of blood and lymphatic vessels, which can cause pain, bleeding, thrombosis, infection, deformity, disability, and death. Evaluating changes in VM-related healthcare-related quality of life (HRQOL) is essential to determining the effectiveness of interventions in clinical trials. However, there is a dearth of HRQOL patient-reported outcome measures (PROMs) that assess VM manifestations in children. In this study, we aim to develop VM-specific PROMs and caregiver-proxy measures that assess HRQOL of children between 4 and 17 years of age with complex VMs. We will include the 3 groups of complex VMs that are the focus of this RDCRC application (PIK3CA-related overgrowth spectrum (PROS) with VMs, complex lymphatic anomalies, and extracranial arteriovenous malformations), as well as low-flow venous and lymphatic malformations. This project will pursue this goal through the following aims. Aim 1: To develop and refine items for Vascular Malformation Quality of Life (VMQOL) measures for children with VMs and family caregiver proxies. We will generate conceptual models of disease- and treatment- related HRQOL domains for children with VMs. We will use concept elicitation methods in qualitative interviews with a wide sample of children with VMs and caregivers (n=72 total interviews) to evaluate the impacts of VMs on HRQOL, treatment goals, and recovery expectations. We will stratify interviews by diagnostic categories, as well as by 3 age ranges: 4-17 years (caregiver interviews), 8-12 years (child interviews), 13-17 years (child interviews). In addition, we will interview at least 8 children and 8 caregivers who preferentially speak Spanish to capture any cultural differences in HRQOL experiences. We will design self-report (for 8-17 year-old children) and caregiver proxy-report (for 4-17 year old children) VMQOL measures in English and Spanish using or modifying existing PROMs, or by developing new measures for HRQOL domains poorly captured by existing PROMs. We will perform iterative rounds of cognitive interviews in English and Spanish to refine items to ensure face and content validity, ease of understanding, and readability. Aim 2. To assess reliability and construct validity of VMQOL measures when administered to children with VMs and caregivers. We will administer the caregiver-proxy and child self-report versions of VMQOL and related measures to caregivers (n=200) and children (n=200) at up to 23 academic medical centers through the Consortium of iNvestigators of Vascular AnomalieS (CaNVAS). We will purposively sample for a range of age, gender, race, ethnicity, and disease. Participants can choose to complete the measures in English or Spanish. Participants will be asked to complete the VMQOL again approximately 2 weeks later to assess test-retest reliability. We will then perform psychometric analysis to assess measure reliability and validity, and we will refine the final VMQOL measure. The development of VMQOL and incorporation into clinical is essential to improving clinical outcomes for children with VMs.