Outcomes reported in pivotal trials may not be considered to be measures of relative effectiveness from a health technology assessment (HTA) or reimbursement perspective. These outcomes (efficacy or safety) are selected to meet the needs of regulatory approval, but may not be optimal for some HTA agencies. A number of factors may be relevant. Trial outcomes may represent physiological parameters, such as tumour response, blood haemoglobin level or lung function, which are not considered to be patient-relevant. However, these may serve as surrogate endpoints (proxies) for effectiveness outcomes of relevance to HTA, but the relationship between the surrogate and ‘final’ endpoint needs to be demonstrated quantitatively. Outcomes that are clinically assessed disease activity indices may be considered measures of effectiveness if they are validated and are widely used. Outcomes that are composite endpoints (for example, MACE: major adverse cardiac events) may need to be disaggregated into their components for consideration in HTA.
RWE Navigator / Introduction to developing medicines / Effectiveness issues: challenges in demonstrating effectiveness / Early / Trial outcomes not considered to be measures of effectiveness