OBJECTIVES: To compare published guidance for population-adjusted indirect treatment comparison (ITC) methods and investigate recent use of these methods – particularly the application of simulated treatment comparisons (STC) with no common comparator, in submissions to the UK’s National Institute for Health and Care Excellence (NICE).

METHODS: STC and matching-adjusted indirect comparison (MAIC) are methods for conducting a population-adjusted ITC that adjust for imbalances in baseline characteristics between study populations. NICE Technical Support Document 18 outlines both STC and MAIC methodologies. However, subsequent guidance in 2020 from NICE's decision support unit (DSU) recommended that “MAICs should not be used under any circumstances”. Published guidance and methods for unanchored and anchored STCs and MAICs were reviewed, as were key publications from simulation studies, testing method performance. Additionally, NICE submissions following the DSU guidance in 2020 were examined to quantify the use of STCs and their acceptance as evidence.

RESULTS: Identified evidence regarding the most appropriate choice of STC or MAIC in the case of an anchored population-adjusted ITC was conflicting. Unanchored MAICs have been tested in a simulation study, however there are far fewer publications reporting implementation of STC in the unanchored scenario. Since the 2020 DSU recommendations were published, there were only four STCs submitted to NICE, of which three were unanchored comparisons and only one unanchored STC formed the ITC base case. Therefore, despite the additional guidance, there have been only a very limited number of submissions to NICE that use STCs, and no further guidance on unanchored methods.

CONCLUSIONS: Although DSU guidance recommended that MAICs should not be used, there is contradictory published evidence on STCs versus MAICs and a lack of guidance about unanchored STCs. With an increasing need to compare data from single arm studies, further research is required on the performance of population adjustment methods, in particular unanchored STCs.