|The cost effectiveness of zanamivir and oseltamivir for influenza treatment
|Armstrong E P, Khan Z M, Perry A S, Perri L R
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.
Two health technologies for the treatment of influenza were considered in the study: zanamivir and oseltamivir, both neuraminidase inhibitors. The former is an orally inhaled powder designed to target delivery to the primary site of viral replication in the lungs and the latter is an orally administered tablet.
Economic study type
The study populations comprised otherwise healthy adults patients suffering from influenza.
The setting was the community. The economic study was carried out in Arizona, USA.
Dates to which data relate
The effectiveness evidence and the resource data were derived from studies carried out between 1996 and 1998. The price year was 2000.
Source of effectiveness data
The effectiveness evidence was derived from a review of published studies.
A decision-analytic model was designed to determine the costs and clinical outcomes related to each neuraminidase inhibitor (oseltamivir and zanamivir) and standard care.
Outcomes assessed in the review
The outcomes assessed in the review and used as input parameters in the model were the probabilities of follow-up physician visits, antibiotics prescription, and adverse reaction. The probability of no complications and the number of symptom-free days were also considered. The probability of hospitalisation was derived from two surveys undertaken in 1996 by the US National Center for Health Statistics.
Study designs and other criteria for inclusion in the review
Only randomised clinical trials were included in the review. Other inclusion criteria were not reported.
Sources searched to identify primary studies
The MEDLINE database was searched to identify published studies evaluating zanamivir and oseltamivir. The key words used were zanamivir, oseltamivir, influenza, and the compound identifier numbers GG167 (zanamivir), and GS4104 and Ro640796 (oseltamivir). The bibliographies of other papers were also searched for relevant publications.
Criteria used to ensure the validity of primary studies
Methods used to judge relevance and validity, and for extracting data
Number of primary studies included
Seven primary studies were included in the review. Two studies provided the effectiveness and resource use data of oseltamivir, and the remaining three studies were used as sources of the effectiveness and resource used data of zanamivir. Two surveys were used to derive the hospitalisation data.
Methods of combining primary studies
A narrative method was used to combine the probability estimates obtained from the primary studies.
Investigation of differences between primary studies
The authors reported some differences between some primary studies, for example, location of the studies and baseline characteristics of the patient population. However, these differences were believed not to have affected the analysis results.
Results of the review
The probability of follow-up physician visits was 0.237 for standard care, and 0.218 for both zanamivir and oseltamivir.
The probability of antibiotics prescription was 0.173 for standard care, 0.134 for zanamivir, and 0.073 for oseltamivir.
The probability of adverse reaction was 0 for the three alternative treatments.
The probability of no complications was 0.746 for standard care, 0.814 for zanamivir, and 0.82 for oseltamivir.
The number of symptom-free days gained over placebo was 1.5 for zanamivir and 1.3 for oseltamivir.
The probability of hospitalisation was 0.01 for standard care, 0.0064 for zanamivir, and 0.0079 for oseltamivir.
Measure of benefits used in the economic analysis
Two benefit measures were used in the economic analysis: the number of successfully treated patients (which was equal to the number of complications averted) and the number of symptom-free days.
Discounting was not carried out, as the costs were incurred over a period of less than one year. The hospitalisation costs included nursing care, acquisition costs for medication, medical procedures and staff costs, central services, laboratory, and radiology, but excluded overheads and charges. Costs of physician visits were also included. These cost estimations were based on actual data and were taken from a published retrospective study. The costs of the drugs were represented by the average wholesale prices. Costs borne by the patients (i.e. costs of OTC medications) were not included. The quantity/cost boundary adopted was that of the hospital. The resource data were gathered between 1997 and 1998. The price year was 2000. Costs and quantities were reported separately.
Statistical analysis of costs
No statistical analysis of costs was reported.
Indirect costs were not included.
One-way sensitivity analyses were carried out to test the robustness of the results. The parameters derived from the literature review, and varied in the model, were the number of symptom-free days, the impact of adverse reactions, the hospitalisation rates, the average length of stay, the diagnostic accuracy, etc.
Estimated benefits used in the economic analysis
The incremental number of successfully treated patients of a drug compared to the standard care was calculated as the probability of no adverse reaction multiplied by the difference in the rate of complication between the antiviral and the standard therapy. This was 0.068 (0.814 minus 0.746) for zanamivir and 0.074 for oseltamivir. The number of symptom-free days gained over placebo was derived from the effectiveness analysis and was 1.5 for zanamivir and 1.3 for oseltamivir.
The total costs in the base case were $53.81 for standard care, $78.15 for zanamivir, and $103.87 for oseltamivir. The incremental cost over standard therapy was $24.34 for zanamivir and $50.06 for oseltamivir.
Synthesis of costs and benefits
An incremental cost-effectiveness analysis was performed in order to combine costs and benefits. The incremental cost per successful patient over standard therapy was $358 for zanamivir and $677 for oseltamivir. The incremental cost per symptom-free day was $16 for zanamivir and $39 for oseltamivir. The incremental monthly cost per member of MCO (estimated in a hypothetical MCO of 100,000 members after the introduction of each neuraminidase inhibitor in the list of formulary drugs) was also calculated. Assuming 1,900 to 9,900 influenza patients having physician visits, the incremental cost per member per month would be $0.46 to $2.41 for zanamivir and $0.95 to $4.95 for oseltamivir. A subgroup of high-risk influenza-positive patients treated with zanamivir was analysed and the cost savings of zanamivir over standard therapy were $77.33 per patient. Sensitivity analyses showed the robustness of the base case results. Only the price of the drugs and the probability of hospitalisation slightly affected the study findings.
Overall, zanamivir was the most cost-effective therapy for influenza-positive patients compared with oseltamivir and standard therapy, across all outcome measures and all scenarios.
CRD COMMENTARY - Selection of comparators
The selection of the comparator of the two main health technologies was clearly based on the routine care for influenza. You should consider whether it represents the current practice in your own setting.
Validity of estimate of measure of effectiveness
The effectiveness measures of the two drugs were derived from a review of clinical trials explicitly carried out to analyse the efficacy of the neuraminidase inhibitors. However, the effectiveness estimates were combined using narrative methods and differences in sample size and population baseline characteristics were not accounted for in the review.
Validity of estimate of measure of benefit
The benefit measures were mainly derived from the effectiveness estimates, raising the same issues as earlier.
Validity of estimate of costs
All costs relevant to the perspective adopted were included in the analysis. Costs and quantities were reported separately. Several sensitivity analyses of quantities, costs, and drug prices were undertaken.
The issue of the generalisability of the results was addressed by carrying out sensitivity analyses on the cost and effectiveness sides of the analysis. However, the authors recognised that the data derived from the zanamivir and the oseltamivir trials could not match perfectly in the model, because of differences in the baseline populations.
Implications of the study
The main implication of the study was that zanamivir proved to be more effective than oseltamivir and standard therapy for the treatment of influenza, resulting in fewer influenza-related complications and more symptom-free days. As a consequence, zanamivir reduced the average number of days needed for employees to return to work in the flu season.
Armstrong E P, Khan Z M, Perry A S, Perri L R. The cost effectiveness of zanamivir and oseltamivir for influenza treatment. Formulary 2000; 35(12): 979-989
Subject indexing assigned by NLM
Amines /chemical synthesis /chemistry /metabolism /pharmacology; Analgesics /chemical synthesis /chemistry /metabolism /pharmacology; Animals; Cerebral Cortex /metabolism; Ligands; Male; Mice; Molecular Structure; Pyridines /chemistry; Rats; Rats, Wistar; Receptors, Nicotinic /drug effects /metabolism
Date bibliographic record published
Date abstract record published