Presentation (CTI)

OBJECTIVES: Real-world evidence (RWE) is increasingly used to support HTA submissions, particularly for rare diseases. When local data are unavailable, ‘non-local’ RWE could be of use. However, demographic, clinical practice, and healthcare system differences often limit the perceived external validity of ‘non-local’ RWE. This study outlines methodological advancements and potential real-world applications of data transportability analyses to address these limitations, with a particular focus on mitigating biases and enhancing decision-grade evidence for HTA.
METHODS: This methodological review identifies key assumptions necessary for transportability, including consistency, positivity, and conditional exchangeability. It highlights the role of matching, weighting, and standardization to address differences between source and target populations. We reviewed prior assessments from CDA-AMC (Canada) and the NICE (UK) to evaluate how transportability analyses might have directly addressed committee concerns regarding external validity.
RESULTS: Our analysis identified several instances where transportability methods could have mitigated bias in submissions using non-local RWE. For example, external control arm data for teclistamab and elranatamab for the treatment of relapsed/refractory multiple myeloma faced criticism from HTA agencies due to differences in treatment regimens and unmeasured prognostic variables relative to the local HTA jurisdiction. Case studies demonstrate that incorporating transportability analyses during study design and submission can enhance the credibility of ‘non-local’ RWE.
CONCLUSIONS: Transportability analyses may be an underused tool offering a rigorous framework for addressing key challenges in adapting non-local RWE to local HTA decision-making. Implementing these methodologies could improve the acceptance of non-local evidence, accelerate patient access to therapies, and support globally harmonized evidence generation and interpretation strategies. Further development of practical guidelines and case studies are essential to standardize these methods and ensure broader adoption in HTA practice.