OBJECTIVES: Health technology assessment (HTA) of new innovative therapies is becoming increasingly challenging; immuno-oncology (IO) therapies are no exception. For example, their distinct clinical profile – long-term responses in a subset of patients – means that HTA agencies increasingly rely on modelling to predict cost-effectiveness. The objective of this study was to explore how different agencies deal with uncertainty and the impact this has on patient access, through a review of assessments involving IO products.

METHODS: HTA dossiers submitted in UK, Canada, Australia, and France for atezolizumab, nivolumab, and pembrolizumab, were reviewed for: adjuvant melanoma and first-line advanced non-small cell lung cancer (monotherapy and combination treatment). Content experts employed a rapid evidence review process to evaluate themes that played significant roles. Two former or current HTA decision-makers from each country were consulted to infer the rationale behind access decisions. We report how HTA agencies managed uncertainty through their deliberations and decisions, and the impact this had on access.

RESULTS: Our research noted divergence across HTA agencies regarding the following sources of uncertainty: (1) role of biomarkers to define the eligible population; (2) extrapolation approaches and length of time horizon; (3) surrogate endpoints; (4) impact of re-treatment. Differences were observed in how HTA agencies dealt with these uncertainties in coming to a decision, including systems they put in place and the type of input they solicit throughout their deliberations. Time to access also varied greatly: registration to reimbursement listing took as little as 4 months in some cases, or up to 20 months in others.

CONCLUSIONS: Differences in how uncertainty was managed impacted cost-effectiveness conclusions and time to access. Understanding reasons behind these differences and analysing how different HTA agencies dealt with uncertainty could help improve efficiency of decision-making for future assessments, and ultimately improve access for patients.