OBJECTIVES

: To assess the use of surrogate outcomes for overall survival (OS) as the final outcome in oncology in final appraisal documents (FAD) published by the National Institute for Health and Care Excellence (NICE) and analyse corresponding post-appraisal evidence to verify the surrogacy assumption.

METHODS

: Relevant FAD were identified by searching the NICE guidance list through April 24^th, 2019. All FAD were screened in a peer-reviewed process and included in the analysis if the appraisal addressed an oncology indication and involved surrogacy assessment for OS. For all included FAD, a targeted literature search was executed to assess if post-appraisal evidence did become available to verify the surrogacy assumption in the FAD.

RESULTS

: Of 429 FAD, 210 had an oncological indication. Of those 210, 19 FAD included surrogacy assessment of which 16 reported OS as the final outcome. Many of the 16 FAD using OS as the final outcome were approved for leukaemia treatment (n=7) and usually used progression‑free‑survival (n=5) or major cytogenetic response (n=3) as the surrogate outcome. Across these 16 FAD, the NICE committee accepted the manufacturer’s assumed surrogacy relationship in 11 FAD, rejected the relationship in 2 FAD and gave inconclusive statements in 3 FAD. After reviewing post-appraisal evidence, evidence supporting the surrogacy was identified for 3 FAD whereas evidence against the surrogacy was found for 2 FAD. For the remaining 11 FAD, evidence of surrogacy was either inconclusive or unavailable. NICE committee recommendation matched post-appraisal evidence in 80% (n=4) of FAD while a mismatch was found in 20% (n=1) of FAD.

CONCLUSIONS

: Using a surrogate outcome to estimate OS is mostly accepted by NICE. Long‑term post‑appraisal data often verifies the committee’s decision reported in the FAD. However, current post‑appraisal data is very limited and not usually intended to validate the surrogacy relationship, thus necessitating further research.