OBJECTIVES: While health technology assessment (HTA) is a key tool in healthcare policy decision-making, HTA requirements regarding clinical evidence vary globally. The objective of this work was to review clinical evidence requirements of HTA agencies in the UK, France, Germany, the US, Canada, Australia and Japan, as well as the new requirements published by EUnetHTA.

METHODS: Based on a comprehensive search of agencies’ websites conducted in June 2023, up-to-date guidelines were extracted and compared.

RESULTS: The guideline’s recommendations provide submitting companies with country-specific details to be followed when working on search strategies, present how the selection should be performed, how to manage discrepancies and conduct a critical appraisal of studies. The most demanding requirements were presented in guidelines issued in the UK and by EUnetHTA. Every agency underlines that clinical data should be collected through a systematic review of the literature. Data from randomized controlled trials are generally preferred. EUnetHTA and HTA agencies from the UK, Germany, Australia, and the US have the most detailed recommendations regarding data sources. Australian agency provides the most detailed guidance on search strategy development, underlining the necessity of combining MESH terms and free-text. Two-level screening is described in guidelines from EUnetHTA, the UK, Germany, the US, Australia, and Japan. Surprisingly, only 4 agencies (from the UK, Germany, the US and EUnetHTA) underline the necessity of performing a double screening. All analysed agencies emphasise the need of performing a quality assessment of included studies.

CONCLUSIONS: Among analysed agencies, there is a consensus on the need to collect clinical evidence in a systematic way, from multiple sources, based on a prespecified research question, alongside with a critical appraisal of identified evidence to ensure maximum bias reduction. Nevertheless, the specific requirements highlight how essential it is for manufacturers to consider local market requirements early enough in the HTA submission strategy development.