OBJECTIVES: Surrogate endpoints are increasingly used to support regulatory approval of new interventions, particularly in the oncology setting where the evaluation of final clinical endpoints such as overall survival (OS) requires long-term follow-up. However, health technology assessment (HTA) agencies have been reluctant to accept surrogate endpoints to demonstrate clinical benefit. This research aimed to evaluate the role of surrogate endpoints in HTA appraisals in oncology in the United Kingdom (UK).
METHODS: All publicly available appraisal documents from the UK National Institute for Health and Care Excellence (NICE) published between October 1, 2019 and October 31, 2022 were reviewed. Appraisals in oncology reporting surrogate endpoint use were identified and key findings extracted.
RESULTS: Surrogate endpoints were used to demonstrate clinical benefit in 25% of the appraisals—primarily in solid tumor (n=18) and hematological (n=8) settings. Surrogate endpoints were mainly used because of immature OS data at the time of the company’s submission; the most frequently used surrogate endpoint was progression-free survival, followed by disease-free survival, minimal residual disease, and response rate. An upward trend on adoption of surrogate endpoints was observed over time (6 appraisals in 2020, 14 appraisals in 2022). Nearly all technologies considering surrogate endpoints were recommended for use by NICE, some via the Cancer Drugs Fund due to uncertain clinical and/or cost-effectiveness evidence. Critiques from the Evidence Review Group focused on the lack of convincing data for robust surrogate relationships between endpoints.
CONCLUSIONS: Though commonly used in oncology to facilitate the evaluation and approval of therapies, surrogate endpoints may increase uncertainty for decision-makers. The use of surrogate endpoints to demonstrate the clinical benefit of a new therapy should rely on a clear rationale for use of a surrogate instead of a hard clinical endpoint, and all the criteria for the validity of the surrogate endpoint should be met.
