OBJECTIVES : Orphan drugs are often approved based on single arms trials, resulting in challenges when estimating relative clinical efficacy. A traditional approach is to use naïve, unadjusted, indirect comparisons, to analyze the comparative effectiveness of interventions. Matching-adjusted indirect comparison (MAIC) is a relatively recently developed tool considered a better alternative to traditional unadjusted ITCs, as it allows for comparisons of different treatment outcomes in a population-matched setting. The aim of this research was to assess the use and acceptance of MAICs in reimbursement desicions of orphan drugs in the EU5 and the Nordics.

METHODS : Orphan drugs with a market authorization in 2017 onwards were included in this research targeting the EU5 countries and the Nordics. The reimbursement assessments reports of the identified orphan drugs were subsequently reviewed.

RESULTS : Search was conducted for more than 33 orphan drugs from each of the reimbursement agencies websites. Only a small proportion of the submissions during the specified time period included a MAIC and in some cases the analysis was presented alongside a head-to-head analysis. MAIC is thus not commonly used and is not always accepted by HTA bodies (e.g. IQWiG). The main challenges associated with its use relate to how comprehensive the variables included should be, as well as to the precision of the results. Nevertheless, given the current landscape on drug development and the increase in single-arm trials, ITCs and MAIC will become more common, and as such, their advantages and challenges should be clearly stated and acknowledged.

CONCLUSIONS : The current study found that even though it is a new method, the use of population adjusted methods in the absence of direct comparisons between treatments has been increasing across different therapeutic areas, and so has its acceptability by HTA bodies, although questions about its validity and correct application remain.