OBJECTIVES: Direct oral anticoagulants (DOACs) are an example of a drug class which received much attention in the literature and from HTA agencies, with much published material. We reviewed real-world evidence (RWE) use in the assessment of DOACs in both pre- and post- regulatory approval stages of their use in the three markets. Our objective was to determine what lessons could be learnt from DOACs to broadly support decision making and faster access to patients.

METHODS: We considered the first four DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) approved for use in atrial fibrillation (AF) in three markets (France, England and Spain). We conducted a pragmatic review of the literature supported by interviews with local experts.

RESULTS: There is a great deal of data, both trial and real-world data (RWD), relating to DOAC effectiveness, providing a ‘best case’ scenario in terms of the wealth of evidence available to answer a range of important questions. These circumstances might be expected to support speedy decision making, reimbursement and patient access. Our results suggest that in practice this was not the case. There were delays in DOAC reimbursement in Spain and France and although there was no delay with reimbursement in England, there was a delay in DOAC implementation and uptake. Our results highlight that significant resources were required to fill gaps in the original DOAC trials to reduce uncertainty and to answer questions important to clinicians, local decision makers and patients using RWE.

CONCLUSIONS: Particular early planning is recommended to support a clearer understanding of the additional evidence needs and to generate RWE that is fit for purpose. In this case, an understanding of key stakeholder issues, local country issues and their prioritisation and a clearer understanding of what additional evidence would be accepted to support decision making should have supported faster access to patients.