Surrogacy and the Valuation of ATMPs: Taking Our Place in the Evidence Generation/Assessment Continuum

Medical technology is advancing rapidly, but established methods for health technology assessment are struggling to keep up. This challenge is particularly stark for the assessment of advanced therapy medicinal products—therapies often launched on the basis of single-arm studies powered to a surrogate primary endpoint. The most robust surrogacy methods investigate trial-level correlations between the treatment effect on the surrogate and the outcome of ultimate interest. However, these methods are often impossible with the evidence usually available for advanced therapy medicinal products at the time of the launch (randomized controlled trials are necessary for these advanced methods). Additionally, these surrogacy relationships are usually considered to be technology specific, adding uncertainty for any approach that primarily relies on historic data to estimate the surrogacy relationship for novel interventions such as advanced therapy medicinal products. The literature has already highlighted the need for early dialogue, staged assessment processes, and pricing arrangements that responsibly share the risk between the manufacturer and payer. However, it is our view that in addition to these critical developments, the modeling methods employed could also improve. Currently, health technology assessment practitioners typically either ignore the surrogate and simply extrapolate the endpoint of greatest patient relevance irrespective of the degree of maturity or assume historic surrogate relationships apply to the novel technology. In this opinion piece, we outline an additional avenue. By drawing on the understanding of the mechanism of action and insights generated earlier in the evidence generation/assessment continuum, cost-effectiveness modelers can make better use of the wider data available. These efforts are expected to reduce uncertainty at the time of the initial launch of pharmaceutical products and increase the value of subsequent data collection efforts.