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There is ongoing debate as to whether conventional pharmacoeconomic evaluation (PE) methods are appropriate for orphan medicinal products (OMPs). The National Centre for Pharmacoeconomics (NCPE) in Ireland has a well-defined process for conducting pharmacoeconomic evaluations of pharmaceuticals, which is the same for OMPs and non-OMPs. The objective of this study was to identify whether supplementary criteria considered in the pharmacoeconomic evaluation of OMPs would affect final reimbursement recommendations.
A literature search was conducted to identify criteria. Orphan drug pharmacoeconomic evaluations completed by the NCPE between January 2015 and December 2017 were identified and supplementary criteria, where feasible, were applied.
Fourteen pharmacoeconomic evaluations were included in the study. Three criteria that could feasibly be applied to the NCPE evaluation process were identified, all three of which essentially broadened the economic perspective of the pharmacoeconomic evaluation. Higher cost-effectiveness threshold: Despite being arbitrarily raised from EUR 45,000/QALY to EUR 100,000/QALY, only one orphan drug demonstrated cost-effectiveness at this higher threshold. Weighted QALY gain: here, a weighted gain of between one and three is applied to drugs demonstrating QALY gains between 10 and 30, respectively. No OMPs included in the study showed a QALY gain of more than 10. Thirteen demonstrated QALY gains less than 10 and one could not be evaluated. Societal perspective: six submissions incorporated societal perspective as a scenario analysis. Despite incremental cost-effectiveness ratios (ICERs) being reduced between 4 percent and 58 percent, only two OMPs demonstrated cost-effectiveness at the higher threshold (EUR 100,000/QALY).
Application of supplementary criteria to the pharmacoeconomic evaluation of OMPs had a minor effect on three products assessed. However, for the majority, the final cost-effectiveness outcomes remained the same. The study highlights that other criteria are being considered in the decision to reimburse.
If you ask anyone what he or she considers to be the greatest environmental problem of our times, it is likely that Climate Change, or something similar to this, will be the reply. The unusual weather patterns – droughts in some parts of the planet, floods in other parts, temperature records (both maxima and minima) being broken, the frequency of cyclones and gales – are associated phenomena. A couple of decades ago, as well as predictions of rising average temperature, another prediction was that there would be more frequent extreme events. So it is not just the trends in warmth or rainfall, or those of the melting of Arctic sea ice or of glaciers, that affect birds, but also the extremes of all aspects of our climate.
Try asking people about their favourite wildlife and almost certainly Birds will feature strongly in the replies. Birds have a charisma which appeals to so many people. Small birds inhabit our gardens and parks, larger birds are a feature of our coasts, estuaries and seas, and the raptors – owls, hawks and eagles – have a particular appeal. Although there are other charismatic and iconic species of wildlife, birds have a particular appeal because they fly by day, occur everywhere and often interact with people because of their endearing habits.
The chain complexes underlying Floer homology theories typically carry a real-valued filtration, allowing one to associate to each Floer homology class a spectral number defined as the infimum of the filtration levels of chains representing that class. These spectral numbers have been studied extensively in the case of Hamiltonian Floer homology by Oh, Schwarz and others. We prove that the spectral number associated to any nonzero Floer homology class is always finite, and that the infimum in the definition of the spectral number is always attained. In the Hamiltonian case, this implies that what is known as the ‘nondegenerate spectrality’ axiom holds on all closed symplectic manifolds. Our proofs are entirely algebraic and apply to any Floer-type theory (including Novikov homology) satisfying certain standard formal properties. The key ingredient is a theorem about the existence of best approximations of arbitrary elements of finitely generated free modules over Novikov rings by elements of prescribed submodules with respect to a certain family of non-Archimedean metrics.
Soils have hardly featured in nature conservation thinking. Criteria have been developed for selecting networks of important Earth science sites, but these have not included criteria for soils.
Above ground, nature conservation has focused on communities of plants and the animals that they support, and criteria have been developed for selecting the ‘best’ sites. There has been scant attention to the soils on which those plant communities depend.
Although species rich, soils do not contain the charismatic species that have been favoured by conservationists. There is no giant panda, corncrake or lady's slipper orchid.
Both the increasing concentration on biodiversity and ‘the ecosystem approach’ are shifting thinking in relation to soils. Despite limited taxonomic knowledge, some attention is being paid to fungi (e.g. the waxcaps, Hygrocybe spp.) and the larger soil-inhabiting invertebrates (e.g. the mole cricket, Gryllotalpa gryllotalpa, and earthworms). The ‘ecosystem approach’ is forcing a more holistic view, focusing on the function of terrestrial ecosystems.
Soils are intimately involved in many ecosystem processes that contribute to the sustainable use of the planet's land resources. The contribution of soils and their biota to sustainable development will ultimately be far more important than the protection of either individual soil types or individual species.
Although it is true that nature conservationists have generally neglected soils, there is one notable exception, that relating to peat soils (e.g. Heathwaite & Göttlich 1990).
Soil has generally been regarded as something of a 'black box' by ecologists. The importance of soil is obvious: it provides physical support for plants, and both the living and non-living components contribute to a variety of important environmental functions. Soil is a species-rich habitat, but many questions about the ecological significance of the soil's biological diversity, and in particular how it affects ecosystem function, have never been asked. The linkages between above-ground ecology, which is rich in ecological theory, and below-ground ecology, where investigation has been restricted by methodological difficulties, have not been made. Technical developments, including isotopic and molecular methods as well as experimental and modelling approaches, have led to a renaissance in soil biodiversity research. The key areas are reflected in this exciting volume which brings together many leading contributors to explore the role and importance of soil biota.
Soil has generally been treated as something of a ‘black box’ by ecologists. It provides the physical support for plants, and both the living and non-living components contribute to a variety of important environmental functions. These include decomposition and the recycling of nutrients, which are both key functions in terrestrial ecosystems. Other roles, such as the breakdown of pollutants and the storage of bioelements, have immense applied significance in a changing environment. Soil provides a habitat for many species of bacteria, fungi, protists and animals; it is generally recognised as a habitat that is species rich. But many questions about the ecological significance of the soil's biological diversity, and in particular how it affects ecosystem function, have never been asked. Until fairly recently this has been because the linkages between above-ground ecology, which is rich in ecological theory, and below-ground ecology, where investigation has been restricted by methodological difficulties, have not been made. It is now time to open the ‘black box’ and to start to understand how it works.
At the end of the twentieth century and with the start of the twenty-first century, efforts have been going on around the world to gain a greater understanding of the diversity of life in the soil and of the functions that these many species perform. In the UK there have been two major programmes of research on biological diversity and the function of soil ecosystems.
A general theory of piecewise multiharmonic splines is constructed for a class of fractals (post-critically finite) that includes the familiar Sierpinski gasket, based on Kigami's theory of Laplacians on these fractals. The spline spaces are the analogues of the spaces of piecewise Cj polynomials of degree 2j + 1 on an interval, with nodes at dyadic rational points. We give explicit algorithms for effectively computing multiharmonic functions (solutions of Δj+1u = 0) and for constructing bases for the spline spaces (for general fractals we need to assume that j is odd), and also for computing inner products of these functions. This enables us to give a finite element method for the approximate solution of fractal differential equations. We give the analogue of Simpson's method for numerical integration on the Sierpinski gasket. We use splines to approximate functions vanishing on the boundary by functions vanishing in a neighbourhood of the boundary.