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.

An analysis of orphan medicine expenditure in Europe: is it sustainable?

BACKGROUND: Orphan medicinal product (OMP) prices are considered by some to be a challenge to the sustainability of healthcare expenditure. These concerns are compounded by the increasing number of OMPs receiving marketing authorisation (MA) annually. The aim of this study was to explore the sustainability of OMP expenditure within the context of total European pharmaceutical expenditure. METHODS: Using historical IQVIA data, an analysis was conducted on total pharmaceutical and OMP expenditure in eight countries (using values / volumes) in the branded, non-branded and overall pharmaceutical market. Country level and aggregated data was considered for EU5 countries, Austria, Belgium and Ireland. Three key analyses were conducted: 1.The OMP share of total pharmaceutical expenditure was calculated from 2000 to 2017, to assess its evolution over time.2.The results of this analysis were compared with a 2011 forecast of OMP budget impact.3.The evolution of the total pharmaceutical market and its different segments (branded OMPs, non-OMP branded and unbranded) were assessed by estimating the compound annual growth rate (CAGR) and percentage of pharmaceutical expenditure for each market segment from 2010 to 2017. RESULTS: Across countries, OMP share of total pharmaceutical expenditure has increased each year since 2000, rising to 7.2% of total pharmaceutical expenditure in 2017. OMP expenditure has increased at a CAGR of 16% since 2010. The number of OMPs receiving MA each year showed a CAGR of 11% since 2001, four percentage points greater than the CAGR for all medicines receiving MA over the same period. OMP share of total pharmaceutical expenditure is higher than forecasted in 2011 due to slower than expected growth in the non-OMP market. OMP growth has been offset by reduced expenditure in the general market and increased use of generics and biosimilars. CONCLUSIONS: Relative spending on OMPs has increased over the last 20 years, but this has been largely compensated for within the current allocation of total pharmaceutical spending by flat expenditure for non-OMPs and increased volumes of (lower-priced) generics/biosimilars, reflecting a shift towards expenditure in higher cost, lower volume patient populations and a shift in drug development towards more specialised targeting of diseases.

Projecting Pharmaceutical Expenditure in EU5 to 2021: Adjusting for the Impact of Discounts and Rebates.

BACKGROUND: Within (European) healthcare systems, the predominant goal for pharmaceutical expenditure is cost containment. This is due to a general belief among healthcare policy makers that pharmaceutical expenditure-driven by high prices-will be unsustainable unless further reforms are enacted. OBJECTIVE: The aim of this paper is to provide more realistic expectations of pharmaceutical expenditure for all key stakeholder groups by estimating pharmaceutical expenditure at 'net' prices. We also aim to estimate any gaps developing between list and net pharmaceutical expenditure for the EU5 countries (i.e. France, Germany, Italy, Spain, and the UK). METHODS: We adjusted an established forecast of pharmaceutical expenditure for the EU5 countries, from 2017 to 2021, by reflecting discounts and rebates not previously considered, i.e. we moved from 'list' to 'net' prices, as far as data were available. RESULTS: We found an increasing divergence between expenditure measured at list and net prices. When the forecasts for the five countries were aggregated, the EU5 (unweighted) average historical growth (2010-2016) rate fell from 3.4% compound annual growth rate at list to 2.5% at net. For the forecast, the net growth rate was estimated at 1.5 versus 2.9% at list. CONCLUSIONS: Our results suggest that future growth in pharmaceutical expenditure in Europe is likely to be (1) lower than previously understood from forecasts based on list prices and (2) below predicted healthcare expenditure growth in Europe and in line with long-term economic growth rates. For policy makers concerned about the sustainability of pharmaceutical expenditure, this study may provide some comfort, in that the perceived problem is not as large as expected.