Orphan drugs and the NHS: Should we value rarity

Cost effectiveness plays an important part in current decisions about the funding of health technologies. Drugs for rare disease (orphan drugs) are often expensive to produce and, by definition, will benefit only small numbers of patients. Several countries have put measures in place to safeguard research and development of orphan drugs, but few get close to meeting the cost effectiveness criteria for funding by healthcare providers. We examine the justifications for special status for rare diseases and ask whether the cost effectiveness of drugs for rare or very rare diseases should be treated differently from that of other drugs and interventions

Drugs for exceptionally rare diseases: a commentary on Hughes et al

Recently in this journal, Hughes and colleagues discussed special funding status to ultra-orphan drugs. They concluded that there should be a uniform policy for the provision of orphan drugs across Europe; that complete restriction was impractical, and that UK policy should aspire to the values of the EU directive on orphan drugs. We critically assess these arguments, demonstrating that they failed to justify special status for treatments for rare diseases

Drugs for exceptionally rare diseases: a commentary on Hughes et al

Recently in this journal, Hughes and colleagues discussed special funding status to ultra-orphan drugs. They concluded that there should be a uniform policy for the provision of orphan drugs across Europe; that complete restriction was impractical, and that UK policy should aspire to the values of the EU directive on orphan drugs. We critically assess these arguments, demonstrating that they failed to justify special status for treatments for rare diseases

Design management of sustainable fashion

The aim of this research is to advance an understanding of how design in the fashion industry can be successfully managed to contribute to environmental sustainability. Its objectives are to investigate how fashion businesses establish and support environmentally sustainable strategies, and how design leaders and managers contribute to the setting of these goals. The paper reviews the literature of the fashion industry, its sustainability strategies, and the management of design. Semi-structured interviews and a quantitative survey of designers was undertaken in the UK. A framework based on the level of business engagement in sustainability was used to structure the thematic analysis of the findings. The research demonstrates the relatively weak influence of designers on sustainable fashion strategy and concludes by developing design management theory for sustainability through a modified Design Atlas framework

First-Principles Calculation of Electric Field Gradients and Hyperfine Couplings in YBa2Cu3O7

The local electronic structure of YBa2Cu3O7 has been calculated using first-principles cluster methods. Several clusters embedded in an appropriate background potential have been investigated. The electric field gradients at the copper and oxygen sites are determined and compared to previous theoretical calculations and experiments. Spin polarized calculations with different spin multiplicities have enabled a detailed study of the spin density distribution to be made and a simultaneous determination of magnetic hyperfine coupling parameters. The contributions from on-site and transferred hyperfine fields have been disentangled with the conclusion that the transferred spin densities essentially are due to nearest neighbour copper ions only with marginal influence of ions further away. This implies that the variant temperature dependencies of the planar copper and oxygen NMR spin-lattice relaxation rates are only compatible with commensurate antiferromagnetic correlations. The theoretical hyperfine parameters are compared with those derived from experimental data.Comment: 14 pages, 12 figures, accepted to appear in EPJ

Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis

OBJECTIVE: To evaluate the cost effectiveness of four disease modifying treatments (interferon betas and glatiramer acetate) for relapsing remitting and secondary progressive multiple sclerosis in the United Kingdom. DESIGN: Modelling cost effectiveness. SETTING: UK NHS. PARTICIPANTS: Patients with relapsing remitting multiple sclerosis and secondary progressive multiple sclerosis. MAIN OUTCOME MEASURES: Cost per quality adjusted life year gained. RESULTS: The base case cost per quality adjusted life year gained by using any of the four treatments ranged from £42 000 ($66 469; 61 630) to £98 000 based on efficacy information in the public domain. Uncertainty analysis suggests that the probability of any of these treatments having a cost effectiveness better than £20 000 at 20 years is below 20%. The key determinants of cost effectiveness were the time horizon, the progression of patients after stopping treatment, differential discount rates, and the price of the treatments. CONCLUSIONS: Cost effectiveness varied markedly between the interventions. Uncertainty around point estimates was substantial. This uncertainty could be reduced by conducting research on the true magnitude of the effect of these drugs, the progression of patients after stopping treatment, the costs of care, and the quality of life of the patients. Price was the key modifiable determinant of the cost effectiveness of these treatments

Mutagens in contaminated soil: a review

The intentional and accidental discharges of toxic pollutants into the lithosphere results in soil contamination. In some cases (e.g., wood preserving wastes, coal-tar, airborne combustion by-products), the contaminated soil constitutes a genotoxic hazard. This work is a comprehensive review of published information on soil mutagenicity. In total, 1312 assessments of genotoxic activity from 118 works were examined. The majority of the assessments (37.6%) employed the Salmonella mutagenicity test with strains TA98 and/or TA100. An additional 37.6% of the assessments employed a variety of plant species (e.g., Tradescantia clone 4430, Vicia faba, Zea mays, Allium cepa) to assess mutagenic activity. The compiled data on Salmonella mutagenicity indicates significant differences (p \u3c 0.0001) in mean potency (revertents per gram dry weight) between industrial, urban, and rural/agricultural sites. Additional analyses showed significant empirical relationships between S9-activated TA98 mutagenicity and soil polycyclic aromatic hydrocarbon (PAH) concentration (r2 = 0.19 to 0.25, p \u3c 0.0001), and between direct-acting TA98 mutagenicity and soil dinitropyrene (DNP) concentration (r2 = 0.87, p \u3c 0.0001). The plant assay data revealed excellent response ranges and significant differences between heavily contaminated, industrial, rural/agricultural, and reference sites, for the anaphase aberration in Allium cepa (direct soil contact) and the waxy locus mutation assay in Zea mays (direct soil contact). The Tradescantia assays appeared to be less responsive, particularly for exposures to aqueous soil leachates. Additional data analyses showed empirical relationships between anaphase aberrations in Allium, or mutations in Arabidopsis, and the 137Cs contamination of soils. Induction of micronuclei in Tradescantia is significantly related to the soil concentration of several metals (e.g., Sb, Cu, Cr, As, Pb, Cd, Ni, Zn). Review of published remediation exercises showed effective removal of genotoxic petrochemical wastes within one year. Remediation of more refractory genotoxic material (e.g., explosives, creosote) frequently showed increases in mutagenic hazard that remained for extended periods. Despite substantial contamination and mutagenic hazards, the risk of adverse effect (e.g., mutation, cancer) in humans or terrestrial biota is difficult to quantify

Efficient Value of Information Calculation Using a Nonparametric Regression Approach: An Applied Perspective

Background: Value-of-information (VOI) analysis provides an analytical framework to assess whether obtaining additional evidence is worthwhile to reduce decision uncertainty. The reporting of VOI measures, particularly the expected value of perfect parameter information (EVPPI) and the expected value of sample information (EVSI), is limited because of the computational burden associated with typical two-level Monte-Carlo–based solution. Recently, a nonparametric regression approach was proposed that allows the estimation of multiparameter EVPPI and EVSI directly from a probabilistic sensitivity analysis sample. Objectives: To demonstrate the value of the nonparametric regression approach in calculating VOI measures in real-world cases and to compare its performance with the standard approach of the Monte-Carlo simulation. Methods: We used the regression approach to calculate EVPPI and EVSI in two models, and compared the results with the estimates obtained via the standard Monte-Carlo simulation. Results: The VOI values from the two approaches were very close; computation using the regression method, however, was faster. Conclusion: The nonparametric regression approach provides an efficient and easy-to-implement alternative for EVPPI and EVSI calculation in economic models

Interdisciplinary educational approaches to clothing longevity

How do we encourage and enable interdisciplinary systems thinking approaches to sustainable fashion design and business education? In preparation for a workshop at the 2017 PLATE conference, this paper introduces the context of a toolkit – The Clothing Durability Dozen (Cooper at al, 2016b) – aimed at enabling students to collaborate and learn about clothing longevity across disciplines and creating a better understanding of the roles that different departments can play in placing sustainable design strategies at the heart of the clothing industry. In line with education for sustainable development (ESD) principles, objectives include stimulating learning and promote core competencies, such as critical and systemic thinking, collaborative decision-making, and taking responsibility for present and future generations. In the workshop, participants will trial and contribute to the development of the toolkit and any necessary supporting material, the final version of which will be available for use as an educational tool