Influenza treatment with neuraminidase inhibitors: cost-effectiveness and cost-utility in healthy adults in the United Kingdom.

We assessed the cost-effectiveness and cost-utility of treating influenza with neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer's and societal perspective in the United Kingdom. A simulation model was developed to predict morbidity and mortality due to influenza and its specified complications, comparing neuraminidase inhibitors with usual care in an otherwise healthy adult population. Robustness of the results was tested by one-way and multiway as well as probabilistic sensitivity analyses. Treatment with either neuraminidase inhibitor results in reduced morbidity and faster return to normal activities. However, oseltamivir dominates zanamivir in cost-utility analysis due to its lower costs. Comparing oseltamivir with usual care, the costs are pound14.36 per day of normal activity gained and pound5,600 per quality-adjusted life-year gained from the healthcare payer perspective. Oseltamivir dominates usual care from the societal perspective. Treatment with oseltamivir is a cost-effective strategy for otherwise healthy adults in the UK from both the healthcare payer and societal perspective.

Medical economics in the field of influenza--past, present and future.

Influenza represents a major challenge for public health worldwide. The burden of suffering is not only reflected by the extent of hospitalisations and deaths arising from this devastating disease, but also by the attributed economic toll. The economics of this disease can, however, be changed favourably due to the availability of efficacious vaccines. Recent studies have demonstrated the economic benefits of vaccinating not only persons at risk, but also healthy working adults. There seems to be an economic advantage even in immunising certain pediatric subpopulations. Only with a clear and transparent body of economic evidence will it be possible to advise health authorities and payors on the utility of influenza vaccination vaccination policies.

Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy.

BACKGROUND: Although antiviral therapy is cost-effective in adults, its cost-effectiveness in older adults has not been studied. OBJECTIVE: To determine the cost-effectiveness of influenza testing and treatment strategies for older adults. DESIGN: Cost-utility decision model. DATA SOURCES: Clinical trials of antiviral drugs and epidemiologic data. TARGET POPULATION: Noninstitutionalized adults older than 65 years of age with influenza-like illness. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Rapid diagnostic testing or empirical therapy with antiviral drugs. OUTCOME MEASURES: Cost per quality-adjusted life-year (QALY) saved. RESULTS OF BASE-CASE ANALYSIS: Compared with no intervention, empirically treating an unvaccinated 75-year-old patient with amantadine increased life expectancy by 0.0014 QALY at a cost of 1.57 dollars, a cost-effectiveness ratio of 1129 dollars per QALY saved. Compared with amantadine, rapid diagnostic testing followed by treatment with oseltamivir cost 5025 dollars per QALY saved and empirical treatment with oseltamivir cost 10,296 dollars per QALY saved. Testing and treatment strategies were less cost-effective if the patient was vaccinated, ranging from 2483 dollars per QALY saved with amantadine to 70,300 dollars per QALY saved with oseltamivir. RESULTS OF SENSITIVITY ANALYSIS: The decision was sensitive to the probability of influenza, the efficacy of oseltamivir in preventing hospitalizations, and hospitalization and case-fatality rates. The decision was not sensitive to the probability or severity of medication side effects, the quality of life for influenza illness or hospitalization, the efficacy of antiviral therapy in shortening influenza illness, or the rapid diagnostic test characteristics. CONCLUSIONS: For unvaccinated or high-risk vaccinated patients during the influenza season, empirical oseltamivir treatment is cost-effective. For other patients, rapid diagnostic testing followed by treatment with oseltamivir is cost-effective. Empirical amantadine treatment offers a low-cost alternative if patients cannot afford oseltamivir.

Logistic issues and potential prescribing costs associated with use of neuraminidase inhibitors for the treatment of influenza in primary care.

In the UK, the National Institute for Clinical Excellence has recommended the use of neuraminidase inhibitors for elderly and at-risk patients who present with influenza-like illness within 36 hours of symptom onset. However, few data exist to enable primary care trusts to evaluate the logistics and costs of prescribing. We sought to determine, during a confirmed influenza outbreak, the proportion of eligible patients who currently present in time to benefit from treatment with a neuraminidase inhibitor, and to develop the findings into a model for evaluating potential prescribing costs. Within a single primary care group, demographic and co-morbidity data were collected on all patients consulting their general practitioner or attending an out-of-hours centre with influenza-like illness during the outbreak period. A typical primary care trust serving 100 000 patients might expect to prescribe a neuraminidase inhibitor to 140 eligible at-risk patients in a season of low influenza activity, rising to 300 in a large epidemic. At-risk patients were more likely than non-at-risk patients to consult within 36 hours of the onset of symptoms. However, only 20% of such patients, rising to 47% in out-of-hours centres, consulted in time to benefit from treatment. The low proportion of elderly and at-risk patients who consult their general practitioner in time to benefit from treatment with a neuraminidase inhibitor emphasizes the overriding importance of annual vaccination in these groups. If the full benefits of neuraminidase inhibitors are to be realized, access to treatment for eligible patients must be improved.

Bedside rapid flu test and zanamivir prescription in healthy working adults: a cost-benefit analysis.

BACKGROUND: Zanamivir, a neuraminidase inhibitor, reduces the number of days of illness in influenza-positive patients. New bedside rapid flu tests (RFT) should increase the number of influenza-positive patients whom receive zanamivir appropriately. OBJECTIVE: To estimate the economic effects of implementing RFT and zanamivir among unvaccinated healthy working adults who consult within 2 days of the onset of influenza-like symptoms. METHODS: We constructed a decision tree to perform a cost-benefit analysis from a societal perspective. Clinical outcome, i.e. number of influenza days averted, and societal costs were compared for three strategies: RFT and conditional zanamivir prescription;systematic zanamivir prescription; and no zanamivir. A two-way sensitivity analysis was performed including the proportion of influenza-positive patients. RESULTS: During influenza epidemics, systematic zanamivir prescription provided the best health outcome (0.81 influenza days averted) and minimised societal costs (reduced by 29.80 US dollars per person compared with no zanamivir; 1999 values). RFT with conditional zanamivir averted 0.65 influenza days and saved 14.40 US dollars per person. When the proportion of influenza-positive patients was under 39%, the no zanamivir strategy yielded the greatest societal savings; otherwise, systematic zanamivir was the dominant strategy. Medical costs associated with no zanamivir were 88.70 US dollars per patient consulting with influenza-like illness, and increased to 125.50 US dollars with systematic zanamivir and to 127.60 US dollars with RFT and conditional zanamivir. CONCLUSIONS: Due to poor sensitivity of current RFT, systematic zanamivir prescription without RFT for unvaccinated healthy working adults should be recommended during influenza epidemics.

Cost-effectiveness of newer treatment strategies for influenza.

PURPOSE: Recent advances in the diagnosis and treatment of influenza, such as rapid testing and neuraminidase inhibitor therapy, are available, but their place in clinical practice and their cost-effectiveness have not been determined. MATERIALS AND METHODS: To estimate the cost-effectiveness of these newer interventions, we used a decision model that compared several influenza management strategies: no testing or treatment, amantadine or rimantadine treatment without testing, testing then amantadine or rimantadine treatment, neuraminidase inhibitor treatment without testing, or testing then neuraminidase inhibitor treatment. Antiviral therapy began within 48 hours in febrile patients with characteristic symptoms of influenza. We assumed that antiviral treatment did not change rates of influenza complication or mortality, and chose parameter values in the baseline analysis to bias slightly against antiviral treatment and toward testing strategies. RESULTS: In the baseline analysis, testing strategies are more expensive and less effective than treatment strategies. Amantadine costs $9.06 per illness day avoided or $11.60 per quality-adjusted day gained. Compared with amantadine, zanamivir costs $198 per illness day avoided or $185 per quality-adjusted day gained, whereas oseltamivir costs $252 per illness day avoided or $235 per quality-adjusted day gained. In elderly patients who require reduced dosage, rimantadine costs $128 per quality-adjusted day gained compared with amantadine. In younger patients, amantadine is favored if the likelihood of influenza A is >67%; otherwise, neuraminidase inhibitors are favored. Testing strategies are more costly and less effective when the influenza probability is >30%. No testing or treatment is favored if the influenza probability is <32% and the influenza utility is >0.77. In elderly patients, amantadine is favored over rimantadine if the utility of medication side effects is >0.94. CONCLUSIONS: Antiviral treatment of influenza without rapid testing is reasonable economically in febrile patients with typical symptoms during influenza season. The choice of antiviral agent depends on age, the likelihood of influenza A, and the willingness to pay per quality-adjusted day gained.

Economic analysis of influenza vaccination and antiviral treatment for healthy working adults.

BACKGROUND: Physicians have several treatment options for influenza, including vaccination and various antiviral therapies. However, the optimal influenza prevention and treatment strategy is unknown. OBJECTIVE: To compare the relative health values of contemporary treatment strategies for influenza in a healthy sample of working adults. DESIGN: Cost-benefit analysis using a decision model. DATA SOURCES: Previously published data. TARGET POPULATION: Healthy employed adults 18 to 50 years of age. TIME HORIZON: A complete influenza season. PERSPECTIVE: Societal. INTERVENTIONS: Eight treatment options (yes or no) based on the possible combinations of vaccination and antiviral therapy (rimantadine, oseltamivir, or zanamivir or no treatment) should infection develop. OUTCOME MEASURES: Cost in U.S. dollars, including the value of symptom relief and medication side effects, which was assigned a monetary value through a conjoint analysis that used a "willingness-to-pay" approach. RESULTS: In the base-case analysis, all strategies for influenza vaccination had a higher net benefit than the nonvaccination strategies. Vaccination and use of rimantadine, the most cost-beneficial strategy, was $30.97 more cost-beneficial than nonvaccination and no use of antiviral medication. The health benefits of most antiviral treatments equaled or exceeded their costs for most scenarios. The choice of the most cost-beneficial antiviral strategy was sensitive to the prevalence of influenza B and to the comparative workdays gained by each antiviral therapy. CONCLUSIONS: Vaccination is cost-beneficial in most influenza seasons in healthy working adults. Although the benefits of antiviral therapy for persons with influenza infection appear to justify its cost, head-to-head trials of the various antiviral therapies are needed to determine the optimal treatment strategy.

Antiviral therapy for influenza virus infections.

Every year, influenza viruses cause global epidemics that result in significant morbidity and mortality. Influenza infections can be serious in children, especially infants and toddlers. Four antiviral agents, amantadine, rimantadine, oseltamivir, and zanamivir, are available for the treatment or prophylaxis of influenza. Experience with the use of these antiviral drugs for influenza in children is limited. Given the small degree of therapeutic gain that is reported from clinical trials, considerations about cost effectiveness are important in deciding whether to use these agents in the treatment of suspected or proven influenza infections in healthy children.

Zanamivir: an update of its use in influenza.

UNLABELLED: Zanamivir is a potent competitive inhibitor of the neuraminidase glycoprotein, which is essential in the infective cycle of influenza A and B viruses. Zanamivir (10mg by inhalation via the Diskhaler twice daily, or 10mg inhaled plus 6.4mg intranasally two or four times daily, for 5 days) reduced the median time to alleviation of major influenza symptoms by up to 2.5 days compared with placebo. Significant reductions of 1 to 2.5 days versus placebo were observed with inhaled zanamivir in phase III trials involving otherwise healthy adults, high-risk patients or children aged 5 to 12 years. Accelerated return to normal activities, and reduced interference with sleep, consumption of relief medication and incidence of complications leading to antibacterial use were also observed with zanamivir. When used for prophylaxis, inhaled zanamivir 10 to 20 mg/day for 10 days to 4 weeks (plus 6.4 mg/day intranasally in one trial) prevented influenza A in 67% of recipients in a university community, significantly reduced the number of families with new cases of influenza compared with placebo or prevented new cases of influenza in long-term care facilities. The tolerability of inhaled or intranasal zanamivir was similar to that of placebo in otherwise healthy adults, high-risk and elderly patients, and children. Recommended dosages of zanamivir did not adversely affect pulmonary function in patients with respiratory disorders in a well-controlled trial, although there have been rare reports of bronchospasm and/or a decline in respiratory function. CONCLUSION: Zanamivir (used within 48 hours of symptom development) reduces the duration of symptomatic illness, causes accelerated return to normal activities or reduces complications requiring antibacterial use in adults, high-risk individuals and children with influenza. Vaccination remains the intervention of choice for prophylaxis in selected populations. However, the efficacy, good tolerability profile and lack of resistance with zanamivir make it a useful option, particularly in those not covered or inadequately protected by vaccination, who are able to use the inhalation device. The use of zanamivir in patients with respiratory disorders remains unclear because of concerns regarding its potential for bronchospasm. Prospective cost-effectiveness analyses and investigations of efficacy in preventing serious complications of influenza, particularly in high-risk patients, are required. Zanamivir shows potential for prophylaxis in persons for whom vaccination is contraindicated or ineffective, in elderly or high-risk patients in long-term care facilities and in households.

Clinical effectiveness and cost effectiveness of zanamivir (Relenza): translating the evidence into clinical practice, a National Institute for Clinical Excellence view.

The UK National Institute for Clinical Excellence (NICE) is charged with the duty of providing informed guidance on clinical practice (clinical effectiveness and cost effectiveness) to patients and health professionals. The Appraisal Committee through its process of review of evidence advises NICE on the clinical effectiveness and cost effectiveness of new and existing technologies and their appropriate use within the National Health Service in England and Wales. The appraisal process takes into account both published and unpublished evidence as well as input from professional and patient and carer groups when coming to its decisions. The appraisal of a new technology often has to bridge the gap between the evidence required for licensing purposes and that needed to provide pragmatic advice to practising clinicians. The appraisal of zanamivir (Relenza) is an excellent working example of this difficult and important process.

Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Zanamivir Study Group.

OBJECTIVE: This study examined the impact of zanamivir treatment on patient morbidity in patients with influenza. DESIGN AND SETTING: This was a multicentre, randomised, double-blind, parallel-group study conducted in 14 countries in Europe and North America during the winter of 1995/1996. PATIENTS AND PARTICIPANTS: The study included 722 individuals with virologically confirmed influenza. INTERVENTIONS: Two different zanamivir treatment regimens [twice daily (bid) or 4 times daily (qid) for 5 days] were compared with placebo. MAIN OUTCOME MEASURES AND RESULTS: Efficacy was measured using a number of patient-assessment questionnaires. Results showed that significantly fewer patients with influenza who were treated with zanamivir had additional contacts with healthcare professionals compared with those who received placebo (8 vs 14%; p < or = 0.049, bid and qid vs placebo). Individuals treated with zanamivir also spent fewer days absent from work (placebo: mean = 3.28 days; qid: mean = 2.52 days; p = 0.031) or college/school (placebo: mean = 2.90 days; bid: mean = 2.24 days; p = 0.032), and showed significant improvements in productivity compared with placebo. The health status questionnaire revealed significant improvements in patient well-being over the first 5 days of the study in those treated with zanamivir compared with those who received placebo. CONCLUSIONS: Zanamivir treatment reduced absenteeism, improved patient productivity and well-being, and reduced the additional use of healthcare resources in patients with influenza.