The cost-effectiveness of dapagliflozin versus sulfonylurea as an add-on to metformin in the treatment of Type 2 diabetes mellitus.

AIMS: To assess the cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, compared with a sulfonylurea, when added to metformin for treatment of UK people with Type 2 diabetes mellitus inadequately controlled on metformin alone. METHODS: Clinical inputs sourced from a head-to-head randomized controlled trial (RCT) informed the Cardiff diabetes decision model. Risk equations developed from the United Kingdom Prospective Diabetes Study (UKPDS) were used in conjunction with the clinical inputs to predict disease progression and the incidence of micro- and macrovascular complications over a lifetime horizon. Cost and utility data were generated to present the incremental cost-effectiveness ratio (ICER) for both treatment arms, and sensitivity and scenario analyses were conducted to assess the impact of uncertainty on the final model results. RESULTS: The dapagliflozin treatment arm was associated with a mean incremental benefit of 0.467 quality-adjusted life years (QALYs) [95% confidence interval (CI): 0.420; 0.665], with an incremental cost of £1246 (95% CI: £613; £1637). This resulted in an ICER point estimate of £2671 per QALY gained. Incremental costs were shown to be insensitive to parameter variation, with only treatment-related weight change having a significant impact on the incremental QALYs. Probabilistic sensitivity analysis determined that dapagliflozin had a 100% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option compared with sulfonylurea from a UK healthcare perspective for people with Type 2 diabetes mellitus who are inadequately controlled on metformin monotherapy.

Cost-effectiveness of dapagliflozin versus DPP-4 inhibitors as an add-on to Metformin in the Treatment of Type 2 Diabetes Mellitus from a UK Healthcare System Perspective.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic, progressive condition where the primary treatment goal is to maintain control of glycated haemoglobin (HbA1c). In order for healthcare decision makers to ensure patients receive the highest standard of care within the available budget, the clinical benefits of each treatment option must be balanced against the economic consequences. The aim of this study was to assess the cost-effectiveness of dapagliflozin, the first-in-class sodium-glucose co-transporter 2 (SGLT2) inhibitor, compared with a dipeptidyl peptidase-4 inhibitor (DPP-4i), when added to metformin for the treatment of patients with T2DM inadequately controlled on metformin alone. METHODS: The previously published and validated Cardiff diabetes model was used as the basis for this economic evaluation, with treatment effect parameters sourced from a systematic review and network meta-analysis. Costs, derived from a UK healthcare system perspective, and quality-adjusted life years (QALYs), were used to present the final outcome as an incremental cost-effectiveness ratio (ICER) over a lifetime horizon. Univariate and probabilistic sensitivity analyses (PSA) were carried out to assess uncertainty in the model results. RESULTS: Compared with DPP-4i, dapagliflozin was associated with a mean incremental benefit of 0.032 QALYs (95% confidence interval [CI]: -0.022, 0.140) and with an incremental cost of £216 (95% CI: £-258, £795). This resulted in an ICER point estimate of £6,761 per QALY gained. Sensitivity analysis determined incremental costs to be insensitive to variation in most parameters, with only the treatment effect on weight having a notable impact on the incremental QALYs; however, there were no scenarios which raised the ICER above £15,000 per QALY. The PSA estimated that dapagliflozin had an 85% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained. CONCLUSIONS: Dapagliflozin in combination with metformin was shown to be a cost-effective treatment option from a UK healthcare system perspective for patients with T2DM who are inadequately controlled on metformin alone.

Is the whole more than the sum of its parts? Evolutionary trade-offs between burst and sustained locomotion in lacertid lizards.

Trade-offs arise when two functional traits impose conflicting demands on the same design trait. Consequently, excellence in one comes at the cost of performance in the other. One of the most widely studied performance trade-offs is the one between sprint speed and endurance. Although biochemical, physiological and (bio)mechanical correlates of either locomotor trait conflict with each other, results at the whole-organism level are mixed. Here, we test whether burst (speed, acceleration) and sustained locomotion (stamina) trade off at both the isolated muscle and whole-organism level among 17 species of lacertid lizards. In addition, we test for a mechanical link between the organismal and muscular (power output, fatigue resistance) performance traits. We find weak evidence for a trade-off between burst and sustained locomotion at the whole-organism level; however, there is a significant trade-off between muscle power output and fatigue resistance in the isolated muscle level. Variation in whole-animal sprint speed can be convincingly explained by variation in muscular power output. The variation in locomotor stamina at the whole-organism level does not relate to the variation in muscle fatigue resistance, suggesting that whole-organism stamina depends not only on muscle contractile performance but probably also on the performance of the circulatory and respiratory systems.

Treatment for life for severe haemophilia A- A cost-utility model for prophylaxis vs. on-demand treatment.

Prophylaxis has been established as the treatment of choice in children with haemophilia and its continuation into the adult years has been shown to decrease morbidity throughout life. The cost of factor therapy has made the option questionable in cost-effectiveness studies. The role of prophylaxis in pharmacokinetic dosage and tolerization against inhibitor formation were used to model the cost utility of prophylaxis vs. on-demand (OD) therapy over a lifetime horizon in severe haemophilia A. The model was applied to a single provider national health system exemplified by the United Kingdom's National Health Service and a third party provider in the United States. The incremental cost-effectiveness ratio (ICER) was estimated and compared to threshold values used by payer agencies to guide reimbursement decisions. A cost per quality-adjusted life year (QALY) was also estimated for Sweden. Prophylaxis was dominant over OD treatment in the UK. The model resulted in an ICER - $68 000 - within the range of treatments reimbursed in the USA. In Sweden, a cost/QALY of SEK 1.1 million was also within the range of reimbursed treatments in that country. Dosage- and treatment-induced inhibitor incidence were the most important variables in the model. Subject to continuing clinical evidence of the effectiveness of pharmacokinetic dosage and the role of prophylaxis in decreasing inhibitor incidence, treatment for life with prophylaxis is a cost-effective therapy, using current criteria for the reimbursement of health care technologies in a number of countries.

Floral volatiles, pollinator sharing and diversification in the fig-wasp mutualism: insights from Ficus natalensis, and its two wasp pollinators (South Africa).

Combining biogeographic, ecological, morphological, molecular and chemical data, we document departure from strict specialization in the fig-pollinating wasp mutualism. We show that the pollinating wasps Elisabethiella stuckenbergi and Elisabethiella socotrensis form a species complex of five lineages in East and Southern Africa. Up to two morphologically distinct lineages were found to co-occur locally in the southern African region. Wasps belonging to a single lineage were frequently the main regional pollinators of several Ficus species. In South Africa, two sister lineages, E. stuckenbergi and E. socotrensis, pollinate Ficus natalensis but only E. stuckenbergi also regularly pollinates Ficus burkei. The two wasp species co-occur in individual trees of F. natalensis throughout KwaZulu-Natal. Floral volatile blends emitted by F. natalensis in KwaZulu-Natal were similar to those emitted by F. burkei and different from those produced by other African Ficus species. The fig odour similarity suggests evolutionary convergence to attract particular wasp species. The observed pattern may result from selection for pollinator sharing among Ficus species. Such a process, with one wasp species regionally pollinating several hosts, but several wasp species pollinating a given Ficus species across its geographical range could play an important role in the evolutionary dynamics of the Ficus-pollinating wasp association.

Phenotypic and genetic divergence among harbour porpoise populations associated with habitat regions in the North Sea and adjacent seas.

Determining the mechanisms that generate population structure is essential to the understanding of speciation and the evolution of biodiversity. Here, we investigate a geographical range that transects two habitat gradients, the North Sea to North Atlantic transition, and the temperate to subpolar regions. We studied the harbour porpoise (Phocoena phocoena), a small odontocete inhabiting both subpolar and temperate waters. To assess differentiation among putative populations, we measured morphological variation at cranial traits (N = 462 individuals) and variation at eight microsatellite loci for 338 of the same individuals from Norwegian, British and Danish waters. Significant morphological differentiation reflected the size of the buccal cavity. Porpoises forage in relatively shallow waters preying mainly on benthic species in British and Danish waters, and on mesopelagic and pelagic fish off the coast of Norway. We suggest that the observed differentiation may be explained by resource specialization and either adaptation or developmental responses to different local habitats.

Parasitoid fig-wasp evolutionary diversification and variation in ecological opportunity.

Ecological processes are manifest in the evolution and form of phenotype diversity. The great abundance of parasitoid species has led to speculation whether rates of speciation and extinction are dependent on parasitoid diversity. If these factors are mutually exclusive, species diversity should fluctuate instead of remaining relatively constant over time. It is not known whether radiations constrained by coevolutionary interactions conform to density-dependent diversification processes. Here we test the prediction that parasitoid fig wasp diversification responds to changes in ecological opportunity and density-independent processes. A phylogenetic approach is used to estimate relative divergence times and infer diversification rate changes using gamma-statistics. Monte Carlo constant rates tests that accommodate incomplete sampling could not reject constant rates diversification. Parasitoid fig wasp diversification is consistent with a more complex explanation than density-dependent cladogenesis. The results suggest contemporary African parasitoid fig wasp diversity remains a legacy of an ancient ecological opportunity facilitated by fig tree diversification following the breakup of Pan-African forests and evolution of the savanna biome over the last 55 Ma and the more recent aridification of the African continent in the last 5 Ma. These results imply that amplified phenotypic differentiation of specialist insects coevolving with plants is coupled to evolutionarily infrequent changes in ecological opportunity.

Taxonomy of the Capensibufo rosei group (Anura: Bufonidae) from South Africa.

A molecular and morphological study of the Mountain Toadlets, previously included in Capensibufo rosei, showed that there are several previously unrecognised species in this group. We describe three new species from the Hawekwas, Hottentots-Holland, Groenland and Riviersonderend Mountains; the DuToitskloof Mountains, and the Akkedis, Koeël and Kleinriviers Mountains, South Africa. Capensibufo rosei is restricted to the Table Mountain chain of the Cape Peninsula.

Pathological findings in harbour porpoises (Phocoena phocoena) from Norwegian and Icelandic waters.

A study of 37 by-caught harbour porpoises from Icelandic and Norwegian waters showed that most were in good or moderate nutritional condition and none was severely emaciated. Mild infection with lungworms (Halocercus invaginatus, Pseudalius inflexus, Torynurus convolutus) was found in 84% of the Icelandic and 91% of the Norwegian animals, usually associated with bronchopneumonia which was rarely severe. Most (91%) of the animals had parasites in the stomach and intestine (Anisakis simplex, Contracaecum osculatum, Pholeter gastrophilus), and Campula oblonga was present in the liver and pancreas of 88 and 21%, respectively. Oesophagitis, gastritis, cholangitis, pericholangitis, pancreatitis and lymphadenitis were almost exclusively associated with parasitic infection and usually mild. Bacterial isolates were obtained from 50 to 55% of the animals but were not considered to be clinically significant. There was no indication of morbillivirus infection. Icelandic and Norwegian animals showed a thicker blubber layer and a lower incidence of severe lesions, especially in the respiratory tract, as compared with reports of by-caught animals from the Baltic Sea.

Efficiency and rationality in the planning of health care for people with AIDS: an application of the balance of care approach. North-East Italian Group for Planning of AIDS Health Care.

OBJECTIVE: To demonstrate the application of an approach for assessing efficiency and rationality in the use of resources for the care of patients with AIDS (PWA), using data for north-east Italy. DESIGN: An economic methodology, the balance of care (BoC) approach, enabled identification of scenarios for the current, planned and recommended provision of care in the study region. METHODS: Data on the supply and utilization of care by PWA across four locations (inpatient care, day care, home care and sheltered accommodation) was collected for a 6-month period during 1994. The current BoC measured in care contacts across the locations was compared with a planned BoC scenario, derived from the Italian AIDS Health Plan, and a recommended BoC scenario based on a delphi expert panel judgement of the appropriate care location according to sets of hypothetical clinical and social characteristics of PWA. The cost consequences of reallocating patient contacts between the current BoC to the recommended BoC was assessed for inpatient and day care contacts. RESULTS: There is an overprovision of home care in the planned BoC scenario if applied to the study region. The cost consequences of a shift of care contacts according to the recommended scenario results in a potential cost reduction of 9.2% compared with the current scenario, and hence an expected efficiency improvement. CONCLUSION: The BoC approach can be applied to improve the efficiency and rationality of resource use in planning care provision for PWA.

An economic evaluation of home-care assistance for AIDS patients: a pilot study in a town in northern Italy.

OBJECTIVE: To evaluate the costs and cost-effectiveness of home-care assistance (HCA) as an alternative to hospital-based care only for patients with AIDS (PWA). DESIGN: A 6-month prospective study. Use of resources by a control group of PWA receiving ordinary hospital-based care (OC group) was compared with that by a random group of PWA who, in addition to hospital care, were also receiving home care (HC group). SETTING: Home- and hospital-based care for PWA in Vicenza, Italy. PATIENTS: HC group selection was based on eligibility criteria for severity of illness, home location and economic and family support. Ten of the PWA satisfying all eligibility criteria were randomly allocated to the HC group. The control group consisted of 32 PWA lacking one or more of the eligibility criteria. INTERVENTION: HCA involved the provision of palliative care for PWA by a multidisciplinary team of caregivers. Hospital-based services covered inpatient and outpatient services. MAIN OUTCOME MEASURE: The health benefits for HC and OC groups using a quantitative quality of life measure (the Quality of Well-Being Scale). RESULTS: Overall health-care cost savings of 6-7%, relative to the OC group, were predicted for the HC group. Costs per well week were estimated at US$482 for the HC group and US$791 for the OC group. CONCLUSION: Home-care assistance appears to be a cost-effective strategy for the treatment and care of PWA if strict eligibility criteria are adhered to.

Economic impact of the AIDS epidemic in the European Community: towards multinational scenarios on hospital care and costs.

OBJECTIVE: To underpin multinational public-health HIV/AIDS strategy planning in the European Community (EC) by integrating national studies on HIV/AIDS in scenario analysis. METHOD: Three types of data are used: routine surveillance data, information on disease progression and observational studies on the economic impact. The HIV/AIDS epidemic is simulated using two models (MIDAS and PC-Based AIDS Scenarios). Selected simulations, consistent with surveillance data, are connected to economic impact (hospital-bed needs and annual hospital costs for AIDS patients). Parameter values expressing per person-year economic impacts are derived from a structured review of publications on economic aspects of AIDS. RESULTS: Evaluation of published studies on hospital resource use and costs in EC countries shows that there are significant differences between both countries and studies, even after conversion to similar measures (for example, using purchasing power parities). These differences are partly due to factors such as the composition of the patient population. Differences in methodology may also have influenced the results. Economic impact is analysed for combinations of three factors; survival time after AIDS diagnosis, hospital inpatient days needed per person-year and corresponding hospital costs per person-year. All scenarios indicate 1995 hospital-bed needs above the 1990 level of 5400 beds. Hospital cost projections for 1995 vary (up to US$1050 million). CONCLUSIONS: (1) For economic impact assessment, there are important gaps in epidemiological and economic data, and in the methods for linking these. (2) Standardization of studies on the resource use and costs of HIV/AIDS is necessary to provide a sound basis for multinational scenarios. (3) Preliminary multinational scenarios show that by 1995 hospital-bed needs for AIDS might reach 0.45% of all hospital beds available in the EC, and that hospital cost projections for AIDS in that year will range from 0.15% to 0.30% of EC health-care expenditure.

Hospital costs of treating haemophilic patients infected with HIV.

OBJECTIVE: To calculate the costs of treating HIV-infected haemophilic patients. DESIGN: Two-year retrospective study of hospital-based resource use and costs, from April 1991 to March 1993. SETTING: Haemophilia Centre and Haemostasis Unit, Royal Free Hospital and School of Medicine, London, UK. PATIENTS: Sixty patients infected with HIV between October 1979 and July 1985. RESULTS: During the 2-year period a total of 1668 hospital visits were made by patients. The mean number of episodes per patient-year (PY) was 0.6 inpatient admissions, 11.5 outpatient visits and 1.8 day cases. The mean cost per PY was 32,528 pounds, with the majority of this spent on clotting factor concentrate products and haemophilia inpatient admissions (81%). A mean cost for HIV-related treatment of 6050 pounds was estimated. The additional cost incurred in switching this group of haemophilic patients from intermediate-purity factor concentrate to high-purity products was 8614 pounds per PY. When clotting factor concentrate and expenditure on haemophilia-related inpatient admissions were excluded, the mean cost of treating HIV infection per PY was 6065 pounds, varying with CD4+ count (< or = 50 x 10(6)/l, 13,093 pounds; 51-200 x 10(6)/l, 6521 pounds; 201-500 x 10(6)/l, 2848 pounds; > 501 x 10(6)/l, 1497 pounds). CONCLUSIONS: CD4+ count may be used as a marker of costs of HIV infection. The HIV-related cost estimates can be used for the planning of current and future hospital-based care in the National Health Service in the United Kingdom. The switch from intermediate-purity factor concentrate to high-purity products has increased the mean HIV-related cost per PY of treating haemophilic patients infected with HIV.

Discounting of health benefits in the pharmacoeconomic analysis of drug therapies: an issue for debate?

In most economic evaluations, future monetary costs and benefits and future health benefits are discounted at the same rate. The purpose of this article is to question such current practice. The primary reason behind discounting costs and benefits is to allow for individuals' preferences over the timing of such events, i.e. to represent social time preference. We argue that the social time preference rate for health benefits is unlikely to be the same as that for monetary costs and benefits. The results of a sensitivity analysis of pharmacoeconomic analyses of drug treatments for hypertension illustrate how the choice of discount rate can affect the conclusions. As no definite conclusions can be drawn regarding the magnitude of the discount rate for health benefits, we recommend that analysts conduct sensitivity analyses employing differential discount rates for health benefits as well as monetary costs and benefits.