OBJECTIVES

For rare diseases and cancers a high demand exists for faster access to novel therapies. Patient populations are often limited in size, making randomized control trials impractical. The number of approvals through accelerated regulatory pathways supported by single-arm trial (SAT) data is increasing. Absence of direct comparators poses HTA challenges. External comparators may provide supporting contextual evidence, however little formal guidance exists on best practices. The aim of this study was to characterise HTA submissions regarding use of external comparators and HTA outcomes.

METHODS

A retrospective descriptive study was conducted using a database of publicly available information on HTA submissions from 2011-2018 covering 32 countries. Original or label extension submissions with SAT and/or other non-RCT supplementary data were selected. Descriptive statistics summarised submission characteristics and outcomes, acceptability of evidence and methodology.

RESULTS

In 17 countries, 179 SAT submissions were identified; 62% (n=112) for oncology indications. SAT submissions were most frequent in France 22% (n=39) and UK 18% (n=32). Frequency increased annually (n= 1 in 2011; n= 53 in 2018). External comparators were used in 52% (n=93) of submissions, most often from RWD (48%, n=45) or prior trials (46%, n=43). A positive HTA outcome was received for 61% (n=57) submissions with external comparators vs 50% (n=33) without. 24% (n=22) of external comparator submissions used an adjusted indirect comparison method with remainder assumed to be naïve comparisons. This analysis will describe country variation in HTA submissions and acceptance based on comparator data provided and analysis approach.

CONCLUSIONS

Use of external comparator data in HTA submissions based on SAT has increased over time. This analysis suggests use of a comparator dataset and analytical method may strengthen the evidence package for positive HTA outcomes. We acknowledge that not all SAT based HTA submissions have been captured in this analysis due to limitation in recording all cases.