Toward Best Practices for Economic Evaluations of Tumor-Agnostic Therapies: A Review of Current Barriers and Solutions

•Evidentiary uncertainty for tumor-agnostic treatments challenges health technology regulation and reimbursement. Few tumor-agnostic therapies have gained market access and their implementation into routine care remains variable. Understanding barriers and solutions to generating economic evidence is critical to enabling timely patient access.•This review finds 3 core challenges creating barriers for decision-grade evidence generation and highlights attempted and proposed solutions equipped to respond to them. The need for real-world evidence combined with life-cycle health technology assessment frameworks emerged as prioritized avenues for managing evidentiary uncertainty.•Challenges and solutions identified in this review will support future validation and consensus-based efforts aligning on necessary data collection, analytic methods, and deliberative frameworks. Combined, these efforts will ensure health technology assessment can sustainably inform patient access to tumor-agnostic therapeutics.