OBJECTIVES: To identify the frequency of the use of external control arms (ECAs) in pharmaceutical submissions to the National Institute for Health and Care Excellence (NICE) for technology appraisals (TAs). Further, to summarize the methods used to derive ECAs in recent TAs by therapeutic area, and to review the considerations of NICE towards the use of ECAs for TAs.

METHODS: The NICE website was searched for TA guidance published from 1 January 2022 through 23 May 2023. The terms “external control,” “observational,” and “real world” were used to narrow the searches, and documents associated with each unique TA identified were reviewed to check whether ECAs were used for the TA. Data were extracted from documents associated with TAs in which ECAs were used.

RESULTS: ECAs were used for 11/132 (8.3%) NICE TAs identified in the review. All TAs identified assessed oncology products investigated in single-arm trials (SATs). ECAs were generated using real-world evidence (n = 8), trial data (n = 1), or both real-world evidence and trial data considered separately (n = 2). The most common techniques used to increase comparability between patients in the SATs and ECAs were matching (n = 5), weighting (n = 5), and restriction (n = 2); multiple techniques were used in 3 TAs. 7/11 (63.6%) NICE TAs in which ECAs were used resulted in positive recommendations for products. The most common feedback on the ECAs, regardless of appraisal outcome, was concern about unresolved differences in characteristics between patients in the SATs and ECAs.

CONCLUSIONS: For TAs of products investigated in SATs, NICE accepts the use of ECAs to generate comparative evidence and recognizes that such analyses may have uncertainties. NICE considers these analyses alongside the suite of evidence submitted for TAs to determine their recommendations.