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

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

THERACOM: a systematic review of the evidence base for interventions to improve Therapeutic Communications between black and minority ethnic populations and staff in specialist mental health services.

PMCID: PMC3599664This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Black and Minority Ethnic (BME) groups in receipt of specialist mental health care have reported higher rates of detention under the mental health act, less use of psychological therapies, and more dissatisfaction. Although many explanations have been put forward to explain this, a failure of therapeutic communications may explain poorer satisfaction, disengagement from services and ethnic variations in access to less coercive care. Interventions that improve therapeutic communications may offer new approaches to tackle ethnic inequalities in experiences and outcomes. METHODS: The THERACOM project is an HTA-funded evidence synthesis review of interventions to improve therapeutic communications between black and minority ethnic patients in contact with specialist mental health services and staff providing those services. This article sets out the protocol methods for a necessarily broad review topic, including appropriate search strategies, dilemmas for classifying different types of therapeutic communications and expectations of the types of interventions to improve them. The review methods will accommodate unexpected types of study and interventions. The findings will be reported in 2013, including a synthesis of the quantitative and grey literature. DISCUSSION: A particular methodological challenge is to identify and rate the quality of many different study types, for example, randomised controlled trials, observational quantitative studies, qualitative studies and case studies, which comprise the full range of hierarchies of evidence. We discuss the preliminary methodological challenges and some solutions. (PROSPERO registration number: CRD42011001661)

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain.health state valuation; HUI-2; SF-6D

Estimating population cardinal health state valuation models from individual ordinal (rank) health state preference data

Ranking exercises have routinely been used as warm-up exercises within health state valuation surveys. Very little use has been made of the information obtained in this process. Instead, research has focussed upon the analysis of health state valuation data obtained using the visual analogue scale, standard gamble and time trade off methods. Thurstone’s law of comparative judgement postulates a stable relationship between ordinal and cardinal preferences, based upon the information provided by pairwise choices. McFadden proposed that this relationship could be modelled by estimating conditional logistic regression models where alternatives had been ranked. In this paper we report the estimation of such models for the Health Utilities Index Mark 2 and the SF-6D. The results are compared to the conventional regression models estimated from standard gamble data, and to the observed mean standard gamble health state valuations. For both the HUI2 and the SF-6D, the models estimated using rank data are broadly comparable to the models estimated on standard gamble data and the predictive performance of these models is close to that of the standard gamble models. Our research indicates that rank data has the potential to provide useful insights into community health state preferences. However, important questions remain

Orphan drugs revisited : [comment]

Hughes et al.1 recently discussed arguments for and against giving special funding status to orphan drugs in this journal. They concluded that there should be a uniform policy across Europe, that complete restriction was impractical, and that UK policy should aspire to the values of the EU directive. The aims of this paper are to correct some inaccuracies in the original paper, develop some of the key issues, and to draw some conclusions regarding the question ‘Do drugs for exceptionally rare disease deserve special status for funding?’ For ease, our paper adopts the same structure as the original

Plane of nutrition affects the phylogenetic diversity and relative abundance of transcriptionally active methanogens in the bovine rumen

peer-reviewedMethane generated during enteric fermentation in ruminant livestock species is a major contributor to global anthropogenic greenhouse gas emissions. A period of moderate feed restriction followed by ad libitum access to feed is widely applied in cattle management to exploit the animal’s compensatory growth potential and reduce feed costs. In the present study, we utilised microbial RNA from rumen digesta samples to assess the phylogenetic diversity of transcriptionally active methanogens from feed-restricted and non-restricted animals. To determine the contribution of different rumen methanogens to methanogenesis during dietary restriction of cattle, we conducted high-throughput mcrA cDNA amplicon sequencing on an Illumina MiSeq and analysed both the abundance and phylogenetic origin of different mcrA cDNA sequences. When compared to their unrestricted contemporaries, in feed-restricted animals, the methanogenic activity, based on mcrA transcript abundance, of Methanobrevibacter gottschalkii clade increased while the methanogenic activity of the Methanobrevibacter ruminantium clade and members of the Methanomassiliicoccaceae family decreased. This study shows that the quantity of feed consumed can evoke large effects on the composition of methanogenically active species in the rumen of cattle. These data potentially have major implications for targeted CH4 mitigation approaches such as anti-methanogen vaccines and/or tailored dietary management