OBJECTIVES: Patient access to new medicines requires regulatory approval from country-specific regulatory and reimbursement HTA bodies. Between March 2000-2018, among all new medicines approved by European Medicines Agency (EMA) only 56% were recommended by the UK’s National Institute for Health and Care Excellence (NICE). The objective of this research was to identify reasons of divergence and understand if greater use and analyses of RWE may have addressed this gap, leading to more NICE recommendations.

METHODS: Systematic search of electronic databases MEDLINE^®, EMBASE^® was undertaken using keywords “HTA”, “regulatory, divergences” and “RWE/D” since database inception.

RESULTS: A total of 9 articles were retrieved. Variation in selection of primary outcome, choice of comparator (active vs. placebo), and use of surrogate outcomes were the key divergent points between regulatory & HTA bodies. These divergences could be addressed by using RWE, integrated throughout product development lifecycle. RWE can be used to support endpoint selection and protocol optimization that may align with HTA expectations. Generating data on additional outcomes and long-term data on primary outcomes (through post-authorization studies using RWD sources) provides relative efficacy data (through RWD derived external controls arm) which is increasingly expected by HTA bodies. However, regulatory and HTA bodies share concerns about quality of RWE. To streamline and align on acceptability of RWE, many regulatory and HTA bodies have developed RWE frameworks, guidance on data quality and study methodology. Duke-Margolis Center for Health Policy recommended “totality of evidence” approach to generating evidence that is informative both for regulators and payers. Early engagement with regulatory and HTA agencies on use of RWE can help addressing reimbursement challenges.

CONCLUSIONS: Establishing early engagement and fostering collaboration between industry, regulatory agencies, and HTA bodies, along with proactive discussions on proper use of RWE to address their feedback, can effectively reduce divergences and expedite patient access to new treatments.