OBJECTIVES: Regulatory incentives for development of antibiotics have increased the number approved by EMA allowing them to come to market based on adapted evidence requirements, challenging the generation of evidence required for health technology assessment (HTA) reimbursement decision making purposes and impeding patient access to effective treatments. We aimed to assess the potential mis-alignment between regulatory approval requirements and HTA requirements for antibiotics in Europe.

METHODS: A targeted review was conducted to identify the appraisal processes and health economic assessment requirements as well as incentive schemes for antibiotics (NICE, SMC, AWMSG, TLV and HAS). To understand the relationship between EMA approvals and HTA body appraisals, a search via the EMA website was performed to identify all antibiotics that were approved since 2013 followed by a search via the HTA body website to identify those that were eventually appraised. Finally, a review of the HTA appraisal challenges with the health economic assessment was performed.

RESULTS: All but NICE appraise innovative antibiotics. Of those, only HAS instituted adapted appraisal criteria for antibiotics. Since 2013, a total of 8 antibiotics were approved by EMA. The SMC appraised all antibiotics on this list (n=8), followed by HAS (n=5), AWMSG (n=4) and TLV (n=3). The appraisals cited the following challenges with the health economic assessment: difficulty in establishing added therapeutic effectiveness due to non-inferiority design, small sample size and uncertainty around treatment effects, short treatment duration hindering lifetime horizon, and choice of comparators. None incorporated the impact of treatment on resistance and spill-over effects.

CONCLUSIONS: HTA processes in Europe need to be adapted for innovative antibiotics to support the regulatory incentives for their development and to accelerate patient access. As a start, traditional requirements for health economic assessment methodology, which does not capture the public health value of antibiotics, should be adapted specifically for antibiotics.