Presentation (CTI)

OBJECTIVES: To characterize how HTAb position and appraise DT-related evidence, and to identify factors influencing its potential acceptability in decision making.
METHODS: A targeted review of HTA documents, including submissions, appraisals, and position statements published between January 2023-April 2026 was conducted across Australia, Canada, the UK, France, Germany, Italy, Spain, the Netherlands and Sweden. Documents were screened using 28 predefined DT-related keywords covering concepts around synthetic or virtual patients or cohorts, and simulated cohorts or trials. Documents containing at least one keyword were manually assessed for relevance and HTAb commentary on evidentiary role, validation and decision-relevance.
RESULTS: Twenty-eight documents containing keywords were identified; Twenty-three were excluded as DT-related keywords referred to standard external control arms, cohort-based economic models, population simulations, or unrelated contexts. Five documents were considered relevant, describing methods simulating individual virtual patient trajectories. One position statement from the Dutch Zorginstituut Nederland (ZIN) positively acknowledged in silico studies in radiotherapy as randomized trials are often difficult or slow. Three submissions to the French Haute Autorité de Santé (HAS) used mechanistic models; one for outcome prediction and two for extrapolation. These were generally considered exploratory and insufficient for decision-making without validation against observed data, although one early-access case accepted modelling-based extrapolation. One submission to the UK National Institute for Health and Care (NICE) used a discrete event simulation (DES) model; the appraisal resulted in a positive recommendation with restrictions to a specific patient population but did not explicitly comment on the DES approach.
CONCLUSIONS: Published HTA experience with DT-related evidence remains limited, and unpublished submissions may have been missed. Available HTA commentary suggests that acceptability depends on DT label and the method’s evidentiary role, transparency, uncertainty characterization, and validation against observed data. Established individual-level simulation methods may provide a bridge for future HTA acceptance of more complex DT approaches when appropriately described and justified.