OBJECTIVES: Rare disease clinical trials often benefit from external control (EC) arms, as randomised controlled trials (RCTs) can be unethical or difficult in terms of patient recruitment. Rather than using unadjusted external controls (static borrowing), it is possible, in underpowered RCTs and single-arm trials, to only borrow relevant external data. This involves either matched borrowing (using propensity score analyses or inverse probability weighting), or dynamic borrowing (where Bayesian dynamic borrowing [BDB] is a key technique). This research aims to summarise National Institute for Health and Care Excellence (NICE) submissions using EC arms and collate recommendations for future submissions using EC data.

METHODS: NICE technology appraisal guidance (TAG) published from December 2016–June 2023, and all existing highly specialised technology (HST) guidance were reviewed, to identify and analyse EC arm usage, and consequently which borrowing method was applied. Using the NICE real-world evidence (RWE) framework, key recommendations were identified for future submissions using dynamic borrowing methods, such as BDB.

RESULTS: Overall, 392 NICE submissions, consisting of 369 TAGs and 23 HSTs, were identified. Of the latter, 17 (74%) presented non-RCT data in their clinical evidence that were relevant to NICE decision-making. Of these, 12/17 (71%) used EC arms. Among them, 5/12 (42%) used matched borrowing methods, with the remaining 7/12 (58%) using static borrowing. Irrespective of the method used, all twelve technologies were recommended by NICE.

CONCLUSIONS: The majority of the NICE submissions that incorporated EC arms used static or matched borrowing, rather than dynamic borrowing. This could have been due to available data not permitting statistically robust dynamic borrowing, or uncertainty in how NICE would view the strength of this method. The recently published NICE RWE framework provides comprehensive guidelines applicable to dynamic borrowing methods, indicating these methods may become more common in future submissions, particularly in rare diseases.