Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer.

PURPOSE: Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany. METHODS: A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim. CONCLUSIONS: Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany.

Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events.

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Mapping breastfeeding services: a method to inform effective implementation and evaluation of evidence-based policy in practice.

This paper aims to introduce a method for mapping local service provision to local demographic and health outcome data, to inform evidence-based policy and practice in public health. A mapping exercise was conducted in London, England with the aims of: (1) describing services provided for breastfeeding women in primary and tertiary health care sectors and government, voluntary and private sectors; and (2) linking this information with routine data on deprivation, breastfeeding rates and health outcomes. Quantitative data on local breastfeeding services were collected via an online questionnaire by a designated 'mapping lead' in each locality. Data were collected at the level of individual health care organisations on the provision, nature and management of breastfeeding services, and related organisational inputs such as leadership, staffing, accreditation and policy. Demographic and health outcome data were identified from existing routine national data collections. Ninety-one per cent of eligible acute and primary care organisations participated in the mapping exercise. A range of mapping tools and profile were developed and launched in 2009 (http://atlas.chimat.org.uk/IAS/dataviews/view?viewId=66). These tools can be used for descriptive analyses of service provision on the basis of local need. Comparative analyses on the impact of service provision on breastfeeding or health outcomes will be feasible from 18 months of data collection onwards. This case study has demonstrated the potential utility of this mapping method to inform effective implementation and evaluation of public health policy in practice consistent with the World Health Organisation framework. Formal evaluation of the utility of the tools is recommended.

Warfarin monitoring economic evaluation of point of care self-monitoring compared to clinic settings.

OBJECTIVE: To determine the cost-effectiveness of home-based point-of-care self-monitoring compared to clinic-based care for patients managed on long-term warfarin medication. Current evidence is inconsistent; results should reduce uncertainty and inform service delivery. METHODS: A Markov model compared self-testing and self-management, using point-of-care devices to usual care in patients with atrial fibrillation and mechanical heart valves. The primary clinical end-points were stroke and mortality avoided; costs and utilities were associated with these events. The costs of warfarin monitoring were included in the model. RESULTS: Over 10 years, self-monitoring saved £1187 per person compared to usual care. Patients who self-monitored had notably fewer strokes and deaths. The results were sensitive to life-years gained and cost of the device. If the NHS purchased the device, financial break-even was achieved at the end of the second year; if the patient bought the device the NHS saved money every year. If 10% of the current 950,000 patients switched to point-of-care devices for 10 years, the NHS could save over £112million. LIMITATIONS: Clinical studies had a relatively short duration and only data on composite end-points were reported. CONCLUSIONS: With training, self-testing and self-management are safe, reliable, and cost-effective for a sizable proportion of patients receiving long-term warfarin. Compared to clinic-based services, self-monitoring offers the NHS the potential to make cost savings and release bed-days by reducing the number of strokes experienced by these high-risk patients.

An economic evaluation of valsartan for post-MI patients in the UK who are not suitable for treatment with ACE inhibitors.

OBJECTIVES: The overall objective of this study was to estimate the costs and outcomes associated with treatment with valsartan for post-myocardial infarction (post-MI) patients with left ventricular systolic dysfunction, heart failure, or both, who are not suitable for treatment with angiotensin-converting enzyme (ACE) inhibitors, compared to placebo. METHODS: A Markov model, using data drawn from the Valsartan in Acute Myocardial Infarction (VALIANT) trial and other trials, was developed to predict the future health pathways, resource use, and costs for patients who have recently experienced an MI. Patients received either valsartan (mean dose 247 mg) or placebo. Cost data were drawn from national databases and published literature, although health outcome utility weights were derived from existing studies. Patient outcomes were modeled for 10 years, and incremental cost-effective ratios were calculated for valsartan compared with placebo. RESULTS: Over a period of 10 years, a cohort of 1000 patients treated with valsartan experienced 147 fewer cardiovascular deaths, 37 fewer nonfatal MIs, and 95 fewer cases of heart failure than a cohort who received placebo. The incremental cost of valsartan, compared with placebo, was 2680 pound per patient, although the incremental effectiveness of valsartan was 0.5021 quality-adjusted life-years (QALYs) gained per patient. Therefore, the incremental cost per QALY for treatment with valsartan was 5338 pound. When analysis was undertaken using life-years rather than QALYs, the cost per life-year gained was 4672 pound. CONCLUSIONS: For patients who are not suitable for treatment with ACE inhibitors, valsartan is a viable and cost-effective treatment for their management after an MI.

An economic evaluation of sevelamer in patients new to dialysis.

OBJECTIVE: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders. METHODS: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service. RESULTS: The total 5-year discounted treatment cost for patients treated with sevelamer is pound 24,216, while for the calcium carbonate group total cost was pound 17,695. This is an incremental cost of pound 6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of pound 27,120 and an incremental cost per life year gained of pound 15,508. Results were similar with calcium acetate. CONCLUSION: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.

A whole system study of intermediate care services for older people.

BACKGROUND: Intermediate care (IC) services have been widely introduced in England and have the strategic objectives of reducing hospital and long-term care use. There is uncertainty about the clinical outcomes of these services and whether their strategic aims will be realised. SETTING: A metropolitan city in northern England. DESIGN: A quasi-experimental study comparing a group of older people before and after the introduction of an IC service. A quota sampling method was used to match the groups. SUBJECTS: Patients presenting as emergency admissions to two elderly care departments with falls, confusion, incontinence or immobility. INTERVENTION: a city-wide service in which a joint care management team (multi-agency, multi-disciplinary) assessed patient need and purchased support and rehabilitation from sector-based IC teams. OUTCOMES: Nottingham Extended Activities of Daily Living score, Barthel Index, Hospital Anxiety and Depression score, mortality, readmission to hospital, and new institutional care placement at 3, 6 and 12 months post-recruitment. RESULTS: There were 800 and 848 patients, respectively, in the control and intervention groups. Clinical outcomes, hospital and long-term care use were similar between the groups. Uptake of IC was lower than anticipated at 29%. An embedded case-control study comparing the 246 patients who received IC with a matched sample from the control group demonstrated similar clinical outcomes but increased hospital bed days used over 12 months (mean +8 days; 95% CI 3.1-13.0). CONCLUSION: This city-wide IC service was associated with similar clinical outcomes but did not achieve its strategic objectives of reducing long-term care and hospital use.

A cost-effectiveness analysis of fluvastatin in patients with diabetes after successful percutaneous coronary intervention.

BACKGROUND: The Lescol Intervention Prevention Study (LIPS) was a multinational randomized controlled trial that showed a 47% reduction in the relative risk of cardiac death and a 22% reduction in major adverse cardiac events (MACEs) from the routine use of fluvastatin, compared with controls, in patients undergoing percutaneous coronary intervention (PCI, defined as angioplasty with or without stents). In this study, MACEs included cardiac death, nonfatal myocardial infarction, and subsequent PCI and coronary artery bypass graft. Diabetes was the greatest risk factor for MACEs. OBJECTIVE: This study estimated the cost-effectiveness of fluvastatin when used for secondary prevention of MACEs after PCI in people with diabetes. METHODS: A post hoc subgroup analysis of patients with diabetes from the LIPS was used to estimate the effectiveness of fluvastatin in reducing myocardial infarction, revascularization, and cardiac death. A probabilistic Markov model was developed using United Kingdom resource and cost data to estimate the additional costs and quality-adjusted life-years (QALYs) gained over 10 years from the perspective of the British National Health Service. The model contained 6 health states, and the transition probabilities were derived from the LIPS data. Crossover from fluvastatin to other lipid-lowering drugs, withdrawal from fluvastatin, and the use of lipid-lowering drugs in the control group were included. RESULTS: In the subgroup of 202 patients with diabetes in the LIPS trial, 18 (15.0%) of 120 fluastatin patients and 21 (25.6%) of 82 control participants were insulin dependent (P = NS). Compared with the control group, patients treated with fluvastatin can expect to gain an additional mean (SD) of 0.196 (0.139) QALY per patient over 10 years (P < 0.001) and will cost the health service an additional mean (SD) of 10 pounds ( 448 pounds) (P = NS) (mean [SD] US $16 [$689]). The additional cost per QALY gained was 51 pounds (US $78). The key determinants of cost-effectiveness included the probabilities of repeat interventions, cardiac death, the cost of fluvastatin, and the time horizon used for the evaluation. CONCLUSION: Fluvastatin was an economically efficient treatment to prevent MACEs in these patients with diabetes undergoing PCI.

A prospective baseline study of frail older people before the introduction of an intermediate care service.

This paper describes the first part of a two-stage research project designed to investigate the clinical and service outcomes of a comprehensive intermediate care service. It is a baseline study of patients presenting to two elderly care departments as emergencies with the clinical syndromes of falls, incontinence, confusion or poor mobility before the introduction of a city-wide intermediate care service. The outcome measures were: mortality; disability (Barthel Index, BI); social activities (Nottingham Extended Activities of Daily Living); service use; and carer distress (General Health Questionnaire -28). These were measured at 3, 6 and 12 months after recruitment. Eight hundred and twenty-three patients were recruited (median age = 84 years; proportion of women = 70%; proportion with cognitive impairment = 45%; median BI score = 15). There was a high mortality rate (36%), evidence for incomplete recovery, a gradual decline in independence over 12 months and a high degree of carer stress. There was little use of rehabilitation services (< 5%), about 25% required readmission to hospital by each assessment point and there was a gradual increase in institutional care admissions. These findings support a needs-based argument for a more comprehensive community service for frail older people.

An economic evaluation of fluvastatin used for the prevention of cardiac events following successful first percutaneous coronary intervention in the UK.

AIMS: To estimate the costs, benefits and cost effectiveness, from the UK NHS perspective, of fluvastatin (relative to no HMG-CoA reductase inhibitor [statin]) for the secondary prevention of major adverse cardiac events following a successful first percutaneous coronary intervention (PCI). METHODS: A cost-effectiveness analysis was undertaken using efficacy data from the Lescol Intervention Prevention Study (LIPS). LIPS was a randomised, double-blind, placebo-controlled trial undertaken in 77 centres (predominantly in Europe). Patients included in the trial had moderate hypercholesterolaemia and had successfully undergone their first PCI. Fluvastatin (Lescol) 40 mg twice daily plus dietary counselling was given to the intervention group for up to 4 years; the control group received dietary counselling only. A Markov model was used to estimate the incremental costs per QALY gained over a 10-year period, with cost data drawn from the UK NHS (2002 values). Monte Carlo simulations and multivariate analysis were used to assess uncertainty. Costs were discounted at 6% per annum, and health outcomes at 1.5% per annum. RESULTS: On average, treatment with fluvastatin cost an additional pound 300 (SD pound 303) [euro 423; SD euro 428] per patient and resulted in an additional 0.092 (SD 0.06) QALYs per patient over 10 years compared with controls. The incremental cost per QALY gained with fluvastatin versus the control group was pound 3207 (SD pound 5,497) [euro 4,527; SD euro 7,759]. Fluvastatin was dominant (better outcomes and lower costs) in 15.9% of the simulations and was dominated in 2.9%. The key determinants of cost effectiveness were: the effectiveness of fluvastatin in reducing acute myocardial infarction, subsequent PCI, coronary artery bypass graft and cardiac deaths; the utility weight associated with a subsequent post-PCI state; the cost of fluvastatin; and the time horizon evaluated. CONCLUSIONS: Fluvastatin is the only statin which has proven effective in preventing major coronary adverse events in new PCI patients; other statins lack this evidence. This Markov model, with its underlying assumptions and data, suggests that fluvastatin is a viable and economically efficient pharmaceutical (relative to no statin) to reduce heart disease in the UK when given routinely to all patients following PCI.

Nectar production rates of Asclepias quadrifolia: causes and consequences of individual variation.

The causes and reproductive consequences of individual variation in nectar production rates within a population of Asclepias quadrifolia were investigated. Two parameters were correlated with nectar production rate per flower: the root weight of the plant and the number of flowers in the inflorescence (umbel). Nectar production increased with increasing root weight but levelled off after a root size of about 3 g was reached. Nectar production decreased with increasing umbel size, but only for umbels that were greater than average size. A total of 57% of the variance in individual nectar production could be explained by these two variables with root weight accounting for 67% of the explained variance. Root weight is a good indicator of a plant's energetic status, indicating the importance of available energy in determining quantity of nectar produced. About 30% of the energy devoted to flowering is utilized in nectar production. Nectar production was significantly correlated with the male component of reproductive fitness, pollinaria removal, but not with the female component, pollinia insertion. Since pod production is limited by resource availability rather than the number of pollinia insertions, nectar production in A. quadrifolia is most closely associated with the maximization of the male function.

An energetic analysis of host plant selection by the large milkweed bug, Oncopeltus fasciatus.

The large milkweed bug, Oncopeltus fasciatus, is a specialized seed feeder that has been observed completing nymphal development in the field on only a small proportion of its potential host species within the genus Asclepias. In central Missouri only two of the six milkweed species studied, A. syriaca and A. verticillata, commonly supported nymphal O. fasciatus growth in the field. The seed of all six species, however, was equally suitable food for bugs reared in the laboratory. In laboratory preference tests, adult bugs chose to feed on the largest seeds, A. hirtella, but such a preference could not explain the observed field feeding patterns.One explanation to account for the observed host plant selection is based upon an energetic analysis. Only A. syriaca provided enough seed biomass for a clutch of O. fasciatus nymphs to develop on a single plant, and only A. verticillata grew in high enough density that a clutch could find sufficient food within the limited range of nymphal movement. These results illustrate a corollary of the resource concentration hypothesis: within a plant group whose members share similar secondary plant chemistries, the only species that will be viable hosts for a specialized herbivore are those that provide the minimal resource density necessary for the completion of nymphal development.In central Missouri, O. fasciatus has specialized on a critical resource density, not traits of individual Asclepias species. The appearance of host selection within the potential host plant spectrum is the result of a characteristic growth form, seed output, and dispersion pattern for each milkweed species that makes some species much more likely than others to produce sufficient seed resources.