Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers

<p>Abstract</p> <p>Background</p> <p>There has been an increase in 'risk sharing' schemes for pharmaceuticals between healthcare institutions and pharmaceutical companies in Europe in recent years as an additional approach to provide continued comprehensive and equitable healthcare. There is though confusion surrounding the terminology as well as concerns with existing schemes.</p> <p>Methods</p> <p>Aliterature review was undertaken to identify existing schemes supplemented with additional internal documents or web-based references known to the authors. This was combined with the extensive knowledge of health authority personnel from 14 different countries and locations involved with these schemes.</p> <p>Results and discussion</p> <p>A large number of 'risk sharing' schemes with pharmaceuticals are in existence incorporating both financial-based models and performance-based/outcomes-based models. In view of this, a new logical definition is proposed. This is "<it>risk sharing' schemes should be considered as agreements concluded by payers and pharmaceutical companies to diminish the impact on payers' budgets for new and existing schemes brought about by uncertainty and/or the need to work within finite budgets</it>". There are a number of concerns with existing schemes. These include potentially high administration costs, lack of transparency, conflicts of interest, and whether health authorities will end up funding an appreciable proportion of a new drug's development costs. In addition, there is a paucity of published evaluations of existing schemes with pharmaceuticals.</p> <p>Conclusion</p> <p>We believe there are only a limited number of situations where 'risk sharing' schemes should be considered as well as factors that should be considered by payers in advance of implementation. This includes their objective, appropriateness, the availability of competent staff to fully evaluate proposed schemes as well as access to IT support. This also includes whether systematic evaluations have been built into proposed schemes.</p

Simulation of perennial ryegrass quality traits using PaSim in a breeding context

Forage quality is important for an efficient uptake and digestion by ruminants. Factors that may limit the animal's ability to reach production goals (high nutritional value of milk and meat) may include the forage's energy and protein content. Moreover, a balanced energy/protein feed can contribute to reduce greenhouse gas emissions from forage protein during digestion. Together with dry matter yield, several quality traits are used as selection criteria in breeding programs of perennial ryegrass (Lolium perenne L.). Though the different components of forage quality have a genetic basis, quality traits are strongly influenced by environmental conditions and their expression varies over the growing season. Consequently, the selection progress is often slow for quality traits because the appreciation of a candidate variety differs largely across years and locations.Modelling approaches can assist here. We refer to the vegetation module of the grassland model PaSim, which simulates different quality traits in response to growing conditions. We investigated whether PaSim can explain the variation in quality traits of candidate varieties of perennial ryegrass throughout the year, and whether model parameter values can be set to characterize each candidate variety.For that, we used a wide set of observations from 65 candidate varieties of the ILVO perennial ryegrass breeding program started in 2012. Observed data from five cutting events in 2013 include: dry matter yield, crude protein content, water soluble carbohydrate content, neutral detergent fiber content (NDF, i.e. cell wall content) and digestible neutral detergent fiber content (NDFD, i.e. cell wall digestibility). Dry matter yield data were also measured in 2014. Model parameter values were estimated for each candidate variety, based on observations and using the parameter optimization function of Package-FME–R Project.This allowed us assigning a set of parameter values to each candidate variety, which can now be evaluated in virtual experiments for a better appreciation of the candidate varieties

Understanding the effect of carbon status on stem diameter variations

Background Carbon assimilation and leaf-to-fruit sugar transport are, along with plant water status, the driving mechanisms for fruit growth. An integrated comprehension of the plant water and carbon relationships is therefore essential to better understand water and dry matter accumulation. Variations in stem diameter result from an integrated response to plant water and carbon status and are as such a valuable source of information. Methods A mechanistic water flow and storage model was used to relate variations in stem diameter to phloem sugar loading and sugar concentration dynamics in tomato. The simulation results were compared with an independent model, simulating phloem sucrose loading at the leaf level based on photosynthesis and sugar metabolism kinetics and enabled a mechanistic interpretation of the ‘one common assimilate pool’ concept for tomato. Key Results Combining stem diameter variation measurements and mechanistic modelling allowed us to distinguish instantaneous dynamics in the plant water relations and gradual variations in plant carbon status. Additionally, the model combined with stem diameter measurements enabled prediction of dynamic variables which are difficult to measure in a continuous and non-destructive way, such as xylem water potential and phloem hydrostatic potential. Finally, dynamics in phloem sugar loading and sugar concentration were distilled from stem diameter variations. Conclusions Stem diameter variations, when used in mechanistic models, have great potential to continuously monitor and interpret plant water and carbon relations under natural growing condition

Understanding the effect of carbon status on stem diameter variations

Background Carbon assimilation and leaf-to-fruit sugar transport are, along with plant water status, the driving mechanisms for fruit growth. An integrated comprehension of the plant water and carbon relationships is therefore essential to better understand water and dry matter accumulation. Variations in stem diameter result from an integrated response to plant water and carbon status and are as such a valuable source of information. Methods A mechanistic water flow and storage model was used to relate variations in stem diameter to phloem sugar loading and sugar concentration dynamics in tomato. The simulation results were compared with an independent model, simulating phloem sucrose loading at the leaf level based on photosynthesis and sugar metabolism kinetics and enabled a mechanistic interpretation of the ‘one common assimilate pool’ concept for tomato. Key Results Combining stem diameter variation measurements and mechanistic modelling allowed us to distinguish instantaneous dynamics in the plant water relations and gradual variations in plant carbon status. Additionally, the model combined with stem diameter measurements enabled prediction of dynamic variables which are difficult to measure in a continuous and non-destructive way, such as xylem water potential and phloem hydrostatic potential. Finally, dynamics in phloem sugar loading and sugar concentration were distilled from stem diameter variations. Conclusions Stem diameter variations, when used in mechanistic models, have great potential to continuously monitor and interpret plant water and carbon relations under natural growing condition

Model-assisted evaluation of crop load effects on stem diameter variations and fruit growth in peach

Key message: The paper identifies and quantifies how crop load influences plant physiological variables that determine stem diameter variations to better understand the effect of crop load on drought stress indicators. Stem diameter (D (stem)) variations have extensively been applied in optimisation strategies for plant-based irrigation scheduling in fruit trees. Two D (stem) derived water status indicators, maximum daily shrinkage (MDS) and daily growth rate (DGR), are however influenced by other factors such as crop load, making it difficult to unambiguously use these indicators in practical irrigation applications. Furthermore, crop load influences the growth of individual fruits, because of competition for assimilates. This paper aims to explain the effect of crop load on DGR, MDS and individual fruit growth in peach using a water and carbon transport model that includes simulation of stem diameter variations. This modelling approach enabled to relate differences in crop load to differences in xylem and phloem water potential components. As such, crop load effects on DGR were attributed to effects on the stem phloem turgor pressure. The effect of crop load on MDS could be explained by the plant water status, the phloem carbon concentration and the elasticity of the tissue. The influence on fruit growth could predominantly be explained by the effect on the early fruit growth stages

Utilisation of antihyperglycaemic drugs in ten European countries: different developments and different levels.

Aims/hypothesis The aim of this study was to compare developments in the utilisation of antihyperglycaemic drugs (AHGDs) in ten European countries. Subhect and methods Data on the yearly utilisation of insulin and oral AHGDs were collected from public registers in Denmark, Finland, Norway, Sweden, Belgium, England, Germany, Italy, Portugal and Spain, and were expressed as defined daily doses per 1,000 inhabitants per day. Results Total AGHD utilisation increased everywhere, but at different rates and levels. Insulin utilisation doubled in England and Germany, but hardly changed in Belgium, Portugal or Italy. Sulfonylurea utilisation doubled in Spain, England and Denmark but was reduced in Germany and Sweden. Metformin utilisation increased greatly everywhere. There were two- to three-fold differences in AHGD utilisation even between neighbouring countries. In Finland, there were more users of both insulin (+120%) and oral AHGDs (+80%) than in Denmark, and the daily oral AHGD doses were higher. In Denmark and Sweden, AHGD utilisation was equal in subjects aged = 45 years of age, both insulin and oral AHGD utilisation were twice as high in Sweden. Conclusions/interpretation The ubiquitous increase in AHGD utilisation, particularly metformin, seems logical, considering the increasing prevalence of type 2 diabetes and the results of the UK Prospective Diabetes Study. However, the large differences even between neighbouring countries are more difficult to explain, and suggest different habits and attitudes in terms of screening and management of type 2 diabetes