Enhancing confidence in complex health technology assessments by using real-world evidence: highlighting existing...

Randomised controlled trials (RCTs) are the gold standard for evaluating new therapies but have limitations, notably in terms of external validity. Real-world data (RWD) studies could complement RCT evidence. However, a consensus has not yet been reached on situations where RWD could offer rigorous complementary evidence to an RCT when evaluating the effectiveness of therapeutic innovations. This research aims to: (1) propose a categorisation of complex clinical situations; (2) classify the real-world evidence (RWE) approaches to be used in each situation to help reduce uncertainties or provide further evidence in drug benefit assessments; (3) summarise the best methodological considerations to adopt when using these RWE approaches; and (4) propose general recommendations to increase confidence in the use of RWE approaches during the assessment process. The main recommendations within the framework around the RWD-generation plan for complex evaluations are related to four main issues: quality (establishing criteria and standards for quality data), methodology (ensuring the use of the best methodological approaches), transparency (from the industry and from the health technology agencies (HTAs) and sharing/collaborating across countries and HTAs (promoting collaboration between HTAs and involving all parties). Our proposal and recommendations could help the scientific community better consider the therapeutic value of innovations through RWD, so that their potential can be fully realised to benefit the quality of care and the regulation of the healthcare system.