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Economic evaluation of antiviral therapy for the treatment of herpes zoster in immunocompetent adults |
Gruger J, Backhouse M E |
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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 Famciclovir as drug therapy for patients with acute shingles and aged 18 years or older.
Economic study type Cost-effectiveness analysis.
Study population Patients aged 18 years or older with acute shingles, who presented for treatment within 48 hours of rash onset.
Setting Secondary and primary care. The economic study was conducted in the UK.
Dates to which data relate The effectiveness data were obtained from a study carried out with patients enrolled between September 1990 and 1991. The resource use data were obtained from a database containing information on patients who were diagnosed in 1991 with at least 2 years' treatment history. The prices were those corresponding to the NHS financial year 1992/93.
Source of effectiveness data Effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was retrospectively undertaken using a different patient sample than that used in the effectiveness analysis.
Study sample It was not reported whether power calculations were used to determine the sample size. The original study consisted of 545 patients randomly allocated to famciclovir 250mg (n=134), famciclovir 500mg (n=134), famciclovir 750mg (n=138), or acyclovir 800mg (n=139). The clinical basis of this study was the trial findings for a subgroup of 117 patients aged over 18 years who began treatment within 48 hours of rash onset.
Study design Randomised, double-blind, controlled trial, carried out in 31 centres in the following countries: Austria, Belgium, Canada, The Netherlands, Spain, Switzerland, the UK, and the former Yugoslavia. The duration of follow-up was 6 months.
Analysis of effectiveness The principle used in the analysis of effectiveness was treatment completers only. The primary health outcomes were of two categories. In the first, the time elapsed after diagnosis before the symptoms had resolved (date at which treatment is successfully completed) was measured so that estimates of successfully treated patients at each point in time within the study period (6 months) were estimated as well as the number of days free of symptoms (SFD). The second outcome measure was the number of days free of pain (PFD), which was estimated by combining data on pain associated with acute (before rash healing) and chronic phases (after rash healing) of shingles.
The Kaplan-Meier Estimator was used to estimate the distribution of time to successful treatment. Then estimates of mean time to successful treatment were calculated as well as the distribution of the other outcome measures. A standard accelerated failure time model with Weibull distribution was used to extrapolate estimates of outcome measures (symptoms-free days (SFD), successfully treated patients (STP), and days free of pain(PFD)) beyond the trial period (6 months) up to 24 months after the start of treatment. The patient groups in the original study were comparable.
Effectiveness results The percentage of successfully treated patients at 6 months was 93.15% with famciclovir, and 89.29% with acyclovir (difference 3.86%, 95% CI: 3.05 - 4.18%). The SFD per patient was 126.04 for famciclovir, and 108.25 for acyclovir (difference 17.79, 95% CI: 17.09 - 18.44). The PFD per patient were 136.68 with famciclovir, and 112.32 with acyclovir (difference 24.36, 95% CI: 23.31 - 25.26).
Clinical conclusions In conclusion, famciclovir, administered less frequently and at lower unit doses than acyclovir, is an effective treatment for patients with uncomplicated herpes zoster.
Measure of benefits used in the economic analysis The number of STPs, SFDs and PFDs were regarded as the main benefit measures. The estimates for the clinical outcome measures were extrapolated to 24 months after diagnosis, by using a standard accelerated failure time model with Weibull distribution.
Direct costs The costs were discounted. The quantities of resource use were reported separately from the prices. The costs measured were operating costs (visits, referrals and drugs) and complication costs (hospital admissions). The boundary adopted was the NHS. The resource use was based on actual data from the Mediplus database (n=1461). The quantities of resource use corresponded to patients diagnosed in 1991. The prices (unit costs) corresponded to those prevailing in the NHS financial year 1992-93.
Sensitivity analysis The variables explored in the analysis were analysed for the cost results and estimate of effectiveness, both alone and combined. The variables explored were the unit costs, a low effectiveness scenario (all patients not successfully treated at the end of the 6-month period would immediately be treated successfully, so that all the differences in effectiveness between strategies are captured in the 6-month period), a high effectiveness scenario (differences in effectiveness persist until 24 months after diagnosis), and the discount rate. A one-way simple sensitivity, best-worst scenario, multi-way sensitivity, and threshold analyses (only for the comparator's price variable) were performed.
Estimated benefits used in the economic analysis All results reported below were discounted at a 6% annual rate. The expected proportion of successfully treated patients at 24 months turned out to be 100% for famciclovir (intervention), and 99.97% for the comparator (difference of 0.03%, 95% CI not reported). The SFD at 24 months after diagnosis per patient of 18 years of age or older and with acute-phase shingles had an expected value of 649.77 for the intervention, whereas, the comparator had an expected value of 625.35 SFDs (difference 24.42, 95% CI: 20.76 - 28.09). The expected number of PFDs per patient with the above-mentioned characteristics was 665.95, for the intervention, and 626.80 for the comparator, both at 24 months after diagnosis (difference 39.15, 95% CI: 33.28 - 45.02).
Cost results The costs were discounted at an annual rate of 6%. The cost per patient with shingles commencing treatment within 24 hours of rash onset was 159.86 for the intervention and 167.42 for the comparator (difference -7.56), at 24 months after diagnosis. The expected undiscounted incremental costs of treating 100 patients (with the characteristics already specified) up to 24 months after diagnosis by using the intervention instead of the comparator were -1685.48. All scenarios and variations in parameters investigated rendered the comparator the more expensive option.
Synthesis of costs and benefits The average and incremental cost-effectiveness ratios were used to combine costs and benefits. The prices were those for the NHS financial year 1992-93, and the discount rate used for both cost and benefit results was 6%. The results are therefore expressed in terms of discounted cost per discounted SFD, discounted cost per discounted PFD, and discounted cost per discounted STP (all at 24 months except when indicated). The intervention resulted in an expected discounted cost per nondiscounted STP of 159.86, whereas the comparator had an expected figure of 167.47. The corresponding figures for the expected discounted costs per discounted SFD were 0.25 and 0.27, respectively. In turn, the expected discounted cost per discounted PFD had values of 0.24, and 0.27, respectively.
The average (undiscounted) cost per STP, SFD, and PFD figures at 6 months, were as follows:
intervention, 166.26, 1.23, and 1.13;
comparator, 179.62, 1.48, and 1.43.
All incremental cost-effectiveness ratios were negative. All scenarios and parameter variations investigated in the sensitivity analyses rendered the comparator a dominated strategy. The threshold analysis demonstrated that (with all other parameters at base case values) a decrease in the cost of acyclovir treatment of 14.84% would produce a positive incremental cost-effectiveness ratio.
Authors' conclusions Famciclovir is probably a dominating strategy over acyclovir in the treatment of acute shingles in immunocompetent individuals of 18 years and more. The analysis may have underestimated the economic benefits to society accruing from the substitution of acyclovir by famciclovir. The implementation of randomised controlled trials with long-term follow-up and quality of life assessments is a desirable step forward following this study.
CRD COMMENTARY - Selection of comparators Aciclovir 800mg 5 times daily for 7 days was chosen as the comparator. You, as a user of this database, should consider whether this is a widely used health technology in your own setting. Validity of estimate of measure of benefit The study results are likely to be internally valid given the use of a randomised design. Validity of estimate of costs The resource quantities were reported separately from the prices and adequate details of methods of cost estimation were given. Since the viewpoint adopted was that of the NHS, no relevant costs appear to have been omitted. The cost analysis was not prospectively performed on the same patient sample as that used in the effectiveness analysis. Other issues The conclusions reached by the authors were justified, given the uncertainties in the data. Implications of the study In view of the fact that there are approximately 270,000 new cases of shingles in adults in the UK annually, the authors calculated that the use of famciclovir 250mg 3 times daily, instead of acyclovir 800mg 5 times daily for 7 days, may result in savings to the NHS of between 550,800 and 4,549,500 per year, depending on the precise pattern of antiviral prescribing practice. Bibliographic details Gruger J, Backhouse M E. Economic evaluation of antiviral therapy for the treatment of herpes zoster in immunocompetent adults. PharmacoEconomics 1997; 11(3): 262-273 Other publications of related interest Degreef H, Famciclovir Herpes Zoster Clinical Study Group. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. International Journal of Antimicrobial Agents 1994;4:241-246.
Indexing Status Subject indexing assigned by NLM MeSH 2-Aminopurine /analogs & Acyclovir /therapeutic use; Adult; Antiviral Agents /therapeutic use; Cost-Benefit Analysis; Double-Blind Method; Drug Costs; Herpes Zoster /drug therapy; Humans; Immunocompetence; derivatives /therapeutic use AccessionNumber 21997008190 Date bibliographic record published 31/12/1999 Date abstract record published 31/12/1999 |
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