OBJECTIVES: Drug repurposing is finding new effective indications for existing drugs, which can save time and costs when developing treatments for unmet medical needs. However, it faces various challenges hindering its full potential. Our aim was to develop a framework of key challenges in drug repurposing and explore how health technology assessment (HTA) can help address these challenges.

METHODS: We reviewed the literature on drug repurposing challenges and drafted a framework by constructing categories and defining links among the identified challenges. We proposed recommendations and development-focused HTA (DF-HTA) methods to overcome these challenges based on HTA literature and our expertise. We assessed the completeness and validity of the framework and the recommendations through a discussion group and semi-structured interviews with experts from the REPO4EU consortium; a European-global platform for mechanism-based drug repurposing, following a thematic analysis approach.

RESULTS: The final framework of drug repurposing challenges was based on 50 research articles, a discussion group with five experts, and seven interviews with 14 experts. The framework identified 20 interconnected challenges grouped into six categories: data access, research, and development (including prioritization), multi-stakeholder collaboration, business case, regulatory, and legal. DF-HTA methods including condition severity, visual mapping of care pathways, and early economic evaluation can support drug repurposing in the prioritization of candidates, research and development, and value proposition in the business case. Other recommendations entail incentivizing data sharing, adaptive clinical trials, incentivizing multi-stakeholder collaboration, shared-risk schemes, flexible regulatory requirements, and identifying patentable compounds and diagnostics.

CONCLUSIONS: The proposed framework helps in understanding drug repurposing challenges and developing targeted measures to overcome them. DF-HTA methods can support drug repurposing when incorporated early in the process by informing decision-making and assessing the value proposition of the repurposed drug.