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Cost effectiveness of oseltamivir treatment for patients with influenza-like illness who are at increased risk for serious complications of influenza: illustration for the Netherlands |
Postma M J, Novak A, Scheijbeler H W, Gyldmark M, van Genugten M L, Wilschut J C |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study examined oseltamivir (75 mg twice daily for 5 consecutive days), a new oral neuraminidase inhibitor for the treatment of both influenza A and B in patients with influenza-like illness (ILI) within 48 hours of the first symptoms. Oseltamivir was compared with conventional symptom and pain relief using over-the-counter analgesic drugs.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised three hypothetical cohorts of at-risk individuals. These were elderly patients (aged 65 years or older) without chronic disease (low-risk, LR), elderly patients with chronic disease (high-risk, HR), and chronically ill, non-elderly patients (HR; adults and children aged over 12 years or adolescents).
Setting The setting was primary care. The economic study was carried out in the Netherlands.
Dates to which data relate The effectiveness data were derived from studies published between 1993 and 2005. The quantities of resources used were obtained from sources published between 1997 and 2005. The price year was 2003.
Source of effectiveness data The clinical inputs used in the model were:
treatment effectiveness (deaths, patients hospitalised, patients receiving antibacterials, working hours lost due to ILI, and average length of stay);
the rates of influenza-related hospitalisations and deaths in patients vaccinated, patients unprotected, and patients with ILI;
life expectancy; and
the risk of death due to ILI complications.
Modelling A decision tree model was developed using two published decision analyses. The structure of the decision tree was represented graphically. The branches with or without oseltamivir were associated with similar events (use of antibacterials, analgesics, hospitalisation or death), but with different probabilities. The time horizon of the model was not explicitly reported, but it might have been an influenza season.
Sources searched to identify primary studies The effectiveness of oseltamivir came from a meta-analysis of clinical trials in different sub-groups of patients. Epidemiological parameters (life expectancy and death risk due to ILI) came from national statistics, while hospitalisation rates came from population studies.
Methods used to judge relevance and validity, and for extracting data No systematic search for data was reported. It is therefore possible that the primary studies might have been identified selectively. However, the use of a published meta-analysis should have ensured a high validity of the primary studies selected for treatment effect.
Measure of benefits used in the economic analysis The summary benefit measure used was the expected number of life-years (LYs). These were estimated using a modelling approach. The LYs were discounted at an annual rate of 4%. The number of deaths averted, hospitalisations and production loss were also reported.
Direct costs The analysis of the costs was carried out from a societal perspective. It included the direct costs associated with inpatient stay (in a normal ward or intensive care unit), antibacterial prescription, oseltamivir prescription and general practitioner visits. The cost of the drugs included the pharmacist's fee. The costs of adverse events were not considered. The unit costs were presented separately from the quantities of resources used. Resource use was derived from published studies, while the costs were estimated according to guidelines for pharmacoeconomic research in the Netherlands on the basis of national average estimated cost prices. Discounting was not relevant given the short timeframe of the analysis.The price year was 2003.
Statistical analysis of costs The costs were treated deterministically in the base-case.
Indirect Costs Productivity costs were included in the analysis as a societal perspective was adopted. The study considered both work absenteeism and loss of efficiency for ill individuals going to work. These resources were conservatively derived from published sources. The friction costing approach was used to value productivity losses, thus the gender and age distribution of the workforce was taken into account using national data. As in the analysis of the direct costs, no discounting was applied and the price year was 2003.
Sensitivity analysis A probabilistic Monte Carlo simulation was undertaken to assess the robustness of the cost-effectiveness results to variations in model inputs. Stochastic distributions were assigned to model parameters. A deterministic sensitivity analysis was carried out for selected variables, such as those that failed to achieve statistical significance in the probabilistic sensitivity analysis or that were unsuited to that analysis (such as the discount rate). Alternative scenarios for the costs and effectiveness were also considered.
Estimated benefits used in the economic analysis In a hypothetical population of 100,000 patients, compared with conventional treatment, oseltamivir averted 19 deaths for HR adolescents and adults, 640 deaths for HR elderly patients, and 122 deaths for LR elderly patients.
The number of hospitalisations with oseltamivir was 806 in HR adolescents and adults, 2,110 in HR elderly, and 367 in LR elderly. The corresponding number of hospitalisations without oseltamivir was 1,284 in HR adolescents and adults, 3,364 in HR elderly, and 584 in LR elderly.
Production loss (number of days lost) for HR adolescents and adults was 325,000 days with conventional treatment versus 243,292 days with oseltamivir.
The LYs gained with oseltamivir were 336 for HR adolescents and adults, 2,963 for HR elderly patients, and 825 for LR elderly patients.
Cost results In a hypothetical population of 100,000 patients, compared with conventional treatment, oseltamivir led to cost-reductions of EUR 11,380 for HR adolescents and adults and EUR 4,907 for HR elderly, and an incremental cost of EUR 1,452 for LR elderly.
The reduction in costs was mainly due to reductions in productivity loss (HR adolescents and adults) and hospitalisations (HR elderly).
Synthesis of costs and benefits Incremental cost-effectiveness ratios were calculated in order to combine the costs and benefits of the alternative strategies.
The incremental analysis revealed that oseltamivir dominated conventional treatment (which was both less effective and more expensive) in both HR populations, while the incremental cost per LY gained with oseltamivir was EUR 1,759 for LR elderly patients.
The probabilistic sensitivity analysis revealed that the probability that oseltamivir dominated conventional treatment was 88% for HR adolescents and adults and 76% for HR elderly patients.
In the population of LR elderly patients, the probability of the incremental cost-effectiveness ratio being below a threshold of EUR 9,338 was 95%.
The deterministic sensitivity analysis suggested that the base-case results were robust to alternative assumptions and scenarios. Only when the indirect savings were excluded from the analysis was oseltamivir no longer dominant in the population of HR adolescents and adults. However, the incremental cost per LY gained was very low (EUR 429).
Authors' conclusions Oseltamivir was cost-effective and even cost-saving in at-risk individuals presenting with influenza-like illness (ILI) to their general practitioner in the Dutch setting.
CRD COMMENTARY - Selection of comparators The rationale for the choice of the comparators was clear in that the new treatment was compared with the conventional pattern of care. However, the authors provided few details of what they considered to be conventional treatment. You should decide whether they are valid comparators in your own setting.
Validity of estimate of measure of effectiveness The effectiveness data used to populate the decision model were derived from published studies. Most of the inputs came from a published meta-analysis of clinical trials, a type of analysis that is usually associated with a high internal validity. However, since no information on the other primary studies was given, it is therefore not possible to make an objective assessment of the validity of the data from the information reported in this paper. Further, it is possible that the primary studies might have been identified selectively, as no details of a systematic review of the literature were reported. The clinical inputs were varied extensively in the sensitivity analysis. Validity of estimate of measure of benefit The summary benefit (LYs) was modelled. Survival was discounted at the recommended rate and the impact of using alternative rates was investigated in the sensitivity analysis. Other outcomes, such as hospitalisations avoided and lost productivity, were also reported.
Validity of estimate of costs The analysis of the costs was consistent with the perspective adopted in the study. Extensive information on the unit costs and quantities of resources used was given, which will allow the current economic analysis to be replicated in other settings. The sources of the data were reported and their selection was justified. Statistical analyses of the costs were not performed, but variations in the cost estimates were investigated in the sensitivity analysis. The cost data were well reported. The price year was reported, which will facilitate reflation exercises in other time periods.
Other issues The authors stated that their findings were in line with those from other published economic evaluations. However, the issue of the generalisability of the study results to other settings was not explicitly addressed, although the extensive use of sensitivity analysis enhances the external validity of the analysis. The results of the base-case analysis and the sensitivity analyses were presented clearly. The authors noted that some conservative assumptions were made, thus the results of the analysis are likely to represent an underestimation of the value for money of oseltamivir. Finally, it was pointed out that the main limitation of the analysis was the lack of evidence on the direct effectiveness of oseltamivir on influenza-related deaths.
Implications of the study The study results support the use of oseltamivir for the treatment of ILI in at-risk individuals, the authors noting that further research should be carried out to define the impact of oseltamivir on mortality.
Source of funding Supported by Roche Nederland BV and Roche Basel.
Bibliographic details Postma M J, Novak A, Scheijbeler H W, Gyldmark M, van Genugten M L, Wilschut J C. Cost effectiveness of oseltamivir treatment for patients with influenza-like illness who are at increased risk for serious complications of influenza: illustration for the Netherlands. PharmacoEconomics 2007; 25(6): 497-509 Other publications of related interest Because readers are likely to encounter and assess individual publications, NHS EED abstracts reflect the original publication as it is written, as a stand-alone paper. Where NHS EED abstractors are able to identify positively that a publication is significantly linked to or informed by other publications, these will be referenced in the text of the abstract and their bibliographic details recorded here for information.
Sander B, Gyldmark M, Aultman R, et al. Impact on health outcome and costs of influenza treatment with oseltamivir in elderly and high-risk patients. J Med Econ 2004;7:67-83.
Rothberg MB, Bellantonio S, Rose DN. Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy. Ann Intern Med 2003;139:321-9.
Reisinger K, Greene G, Aultman R, et al. Effect of influenza treatment with oseltamivir on health outcome and costs in otherwise healthy children. Clin Drug Invest 2004;24:395-407.
Indexing Status Subject indexing assigned by NLM MeSH Aged; Antiviral Agents /economics /therapeutic use; Chronic Disease; Cost of Illness; Cost-Benefit Analysis; Female; Humans; Influenza, Human /drug therapy /economics /epidemiology; Male; Models, Economic; Netherlands /epidemiology; Oseltamivir /economics /therapeutic use; Risk AccessionNumber 22007001410 Date bibliographic record published 30/11/2007 Date abstract record published 30/11/2007 |
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