OBJECTIVES: The emergence of CRISPR-based interventions (CBI) promises to revolutionize treatment of several diseases. To optimize patient access, anticipating and mitigating health technology assessment (HTA) challenges will be crucial.

METHODS: Interventional clinical trials of CBI were identified from clinicaltrials.gov and the main characteristics synthesized. Separately, all available NICE technology appraisals of gene therapies were reviewed. Commentary on trial design, incorporation of real-world evidence (RWE), extrapolation of trial outcomes, and indirect treatment comparison (ITC) methodology were captured and implications for CBI assessed.

RESULTS: We identified 58 CBI trials across various indications, primarily oncology (n=29). Most were for advanced diseases and included highly specific patient populations. The majority were single-arm trials and none were designed to generate direct comparative evidence against standard of care.

CONCLUSIONS: While CBIs are transforming the clinical landscape, payers still need to be convinced of the comparative clinical and cost-effectiveness of CBIs. Existing gene therapy reviews suggest that current evidence generation approaches for innovative therapies are often scrutinized by payers. Manufacturers of CBIs will need to evolve evidence generation strategies to avoid bottlenecks in patient access to innovative and potentially curative treatments.