OBJECTIVES: In recent years, the healthcare industry has witnessed a trend for regulatory approvals of innovative technologies in oncology without head-to-head clinical trial evidence or Health Related Quality-of-Life (HRQoL) data. This yields a challenge to decision-makers who require a cost-effectiveness analysis (CEA) to conduct Health Technology Assessments. To demonstrate methodological approaches and potential data sources to address these gaps, we present a case study using recently approved drugs lenvatinib and sorafenib for management of radioiodine-refractory differentiated thyroid cancer (RR-DTC). METHODS: A vignette study was conducted to elicit utilities for RR-DTC health-states and estimate the impact of toxicities on HRQoL. Phase III clinical trial data with crossover correction were used to compare clinical-endpoints of Progression Free Survival (PFS) and Overall Survival (OS) for both lenvatinib and sorafenib. Adjustments for study population differences were addressed using Matching-Adjusted Indirect Comparison