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Economic analysis of oral and topical therapies for onychomycosis of the toenails and fingernails |
Casciano J, Amaya K, Doyle J, Arikian S, Shear N, Haspel M, Kahler K |
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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 Four antifungal agents for the treatment of onychomycosis of the toenails and fingernails were considered. The oral and topical therapies assessed were itraconazole-continuous, itraconazole-pulse, terbinafine and ciclopirox.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of adult patients with onychomycosis of the toenails or fingernails. Patients with concurrent psoriasis of the nails were excluded from the study evaluation, as were those immunocompromised. Also excluded were patients with onychomycosis caused by yeast or mould.
Setting The setting was unclear, but it was likely to have been primary care. The economic analysis was carried out in the USA.
Dates to which data relate The effectiveness data were gathered from studies published between 1985 and 2001. The resource data were defined by a panel of expert dermatologists. The price year was 1997.
Source of effectiveness data The effectiveness data were derived from a meta-analysis, based on published studies and expert opinion. The present meta-analysis was an update of a published meta-analysis by Marchetti et al. (see Other Publications of Related Interest).
Modelling A decision analytic model was created to simulate the costs and the health outcomes assigned to each treatment strategy. The time horizon was 3 years for toenail and 2 years for fingernail.
Outcomes assessed in the review The outcomes assessed in the meta-analysis and used as model inputs were the rates of success, failure and relapse. The rate of adverse events was also reported. Success was defined as mycological cure, defined as a negative microscopy examination in potassium hydroxide and negative culture. Relapse was defined as a recurrence of the infection within 1 month after an initial success.
Study designs and other criteria for inclusion in the review The authors included randomised, double-blind, comparative trials where possible. A limited number of open-label trials was also included in the meta-analysis. The inclusion criteria specified:
adult patients;
onychomycosis or tinea unguium caused by dermatophytes;
success defined as mycological cure only;
dosage and treatment lengths within currently suggested ranges; and
success recorder as per protocol.
The exclusion criteria were onychomycosis caused by yeast or mould, immunocompromised patients, and patients with concurrent psoriasis of the nails.
Sources searched to identify primary studies MEDLINE and EMBASE were searched for primary studies. English language articles from 1985 to 2001 were reviewed.
Criteria used to ensure the validity of primary studies The criteria used to ensure the validity of the primary studies were the study design criteria (i.e. randomised, double-blind, comparative trials).
Methods used to judge relevance and validity, and for extracting data Since open-label trials were also included, heterogeneity tests were conducted so as to minimise bias in the results. Two separate investigators extracted the data independently.
Number of primary studies included Approximately 40 clinical trials were included in the review. These trials reported data from 3,248 patients.
Methods of combining primary studies The results of the individual primary studies were combined using a meta-analysis.
Investigation of differences between primary studies The authors reported that consensus about differences between the studies was reached through discussion.
Results of the review The success rates were:
with itraconazole-continuous, 0.926 for fingernail and 0.645 for toenail;
with itraconazole-pulse, 0.793 for fingernail and 0.565 for toenail;
with terbinafine, 0.965 for fingernail and 0.811 for toenail; and
with ciclopirox, 0.321 for toenail (the success rate for fingernail was based on an assumption, see below).
The relapse rates were 0.263 with itraconazole-continuous, 0.176 with itraconazole-pulse, and 0.064 with terbinafine.
No adverse events leading to the discontinuation of ciclopirox treatment were reported. For itraconazole-continuous, the most common reactions were elevated liver enzymes (4.0%) and rash (3.0%). With terbinafine, the most commonly reported adverse events were rash and visual disturbance (both 0.9%).
Methods used to derive estimates of effectiveness Published data on the use of ciclopirox for treating fingernails were unavailable. Therefore, the authors assumed that the efficacy of an oral agent could be used to extrapolate and estimate the efficacy of a topical agent on fingernails. The authors also assumed the relapse rate for ciclopirox. This assumption was derived from a published meta-analysis (Gupta et al., see Other Publications of Related Interest).
Estimates of effectiveness and key assumptions The success rate of ciclopirox in fingernail treatment was estimated to be 0.431 (a 34.28% improvement over the toenail efficacy rate, as observed between toenail and fingernail for the other agents). The relapse rate for ciclopirox was assumed to be 0.207.
Measure of benefits used in the economic analysis The benefit measure used was the number of disease-free days (DFDs) for each therapy. DFDs were used as a proxy for quality of life in the absence of prospectively determined quality of life.
Direct costs The perspective of a third-party payer was adopted. The categories of costs included were drug, routine medical care (including laboratory testing) and the treatment of adverse events. The drug costs consisted of the drug acquisition cost and were derived by applying 2001 Red Book average wholesale prices. Routine medical care consisted of all visits, procedures, and tests necessary for treatment and monitoring. The quantities and the unit costs were reported separately. The resource data were defined by a panel of expert dermatologists. The unit costs were derived from public and proprietary sources (i.e. HCFA, NCHS and UCR fee schedules). The price year was 1997. The costs were not discounted.
Statistical analysis of costs No statistical analysis of the costs was performed.
Indirect Costs The indirect costs were not included.
Sensitivity analysis Univariate sensitivity analyses were performed. These used the rank order stability analysis on key parameters such as success rates, drug prices, medical care cost and length of treatment. The efficacy rates were varied within the 95% confidence intervals, based on a truncated normal distribution. The unit costs were varied within +/- 15%, based on a uniform distribution.
Estimated benefits used in the economic analysis Terbinafine yielded the highest number of DFDs (844) for toenail infections, followed by itraconazole-continuous (817), itraconazole-pulse (805) and ciclopirox (511).
Terbinafine also yielded the highest number of DFDs for fingernail infections (622), followed by itraconazole-pulse (594), itraconazole-continuous (562) and ciclopirox (452).
Cost results Terbinafine had the lowest overall expected cost ($755) for fingernail infections, followed by ciclopirox ($854), itraconazole-pulse ($1,136) and itraconazole-continuous ($1,395).
Ciclopirox had the lowest overall expected cost ($1,568) for toenail infections, closely followed by terbinafine ($1,574) then itraconazole-pulse ($1,796) and itraconazole-continuous ($2,566).
Synthesis of costs and benefits Terbinafine was the most cost-effective alternative for the treatment of both fingernails and toenails. For fingernail treatment, terbinafine was both more effective and less costly than the other treatment strategies. For toenail treatment, the number of DFDs associated with terbinafine treatment largely compensated for its higher costs in comparison with ciclopirox treatment.
The authors reported the average cost per DFD for each strategy.
Terbinafine provided the most favourable average cost per DFD ($1.86/DFD) for toenails, followed by itraconazole-pulse ($2.23/DFD), ciclopirox ($3.07/DFD) and itraconazole-continuous ($3.14/DFD).
Terbinafine also provided the most favourable average cost per DFD ($1.21/DFD) for fingernails, followed by ciclopirox ($1.89/DFD), itraconazole-pulse ($1.91/DFD) and itraconazole-continuous ($2.48/DFD).
The sensitivity analysis demonstrated stability across all scenarios. The results were more sensitive to the efficacy of terbinafine than to the efficacy of the other agents.
The authors reported the results of the budget impact analysis. For a population of 1,010,000 individuals, 4% would suffer from onychomycosis and, of these, 10% would receive treatment. Thus, increasing terbinafine use from 0 to 100% was expected to yield total annual savings of $535,165 ($0.16 per member per month).
Authors' conclusions Terbinafine is the most cost-effective therapy in the treatment of onychomycosis from a managed care perspective. At the policy level, increased use of terbinafine among onychomycosis patients is likely to reduce the managed care organisations' cost per member per month.
CRD COMMENTARY - Selection of comparators The selection of the comparators was implicitly justified, as all of them represented established antifungal agents for the treatment of onychomycosis of the toenails and fingernails. A comparison with no treatment would have allowed the additional effectiveness and cost-effectiveness of antifungal agents to be evaluated. You should consider whether any of the comparators used in the analysis represent widely used health technologies in your own setting.
Validity of estimate of measure of effectiveness Although not explicitly stated, it is likely that a systematic review of the literature was undertaken. The methods and conduct of the review were adequately reported. The effectiveness estimates from the primary studies were combined through a meta-analysis. The sources searched and the criteria used to ensure the validity of the primary studies were reported, as was the method used to judge the relevance and validity of the data. Sensitivity analyses, in which the values of the effectiveness estimators were varied, were performed. This enhanced the validity of the results. However, it was unclear whether all of the authors' assumptions were tested in a sensitivity analysis.
Validity of estimate of measure of benefit The estimation of benefits was modelled. The authors did not describe in detail the decision analytic model they used for this purpose, thus it was unclear whether it was appropriate.
Validity of estimate of costs The perspective of the study was explicitly stated and was that of a third-party payer. All the categories of cost relevant to this perspective were included in the analysis. The resource quantities were derived from a panel of expert dermatologists and were reported separately from the prices. Statistical tests were not carried out and the costs were treated deterministically. A sensitivity analysis of the costs was undertaken, based on a range of values that was not justified (+/- 15%). The year to which the prices referred was reported, which aids the reproducibility of the results. The costs for fingernail infections were incurred during two years or less, therefore discounting was appropriately not undertaken. However, for toenail infections the time horizon was 3 years. Discounting would therefore have been appropriate, but it was not undertaken.
Other issues The authors did not compare their findings with those of other studies. The issue of generalisability to other settings was not addressed. The authors emphasised that the costs related to the different strategies predicted by their model reflected an ideal situation. In real-world settings, misdiagnosis can lead to variations in cost results. The results of the analysis were reported in full and the authors' conclusions reflected the scope of the analysis.
The authors did not calculate the incremental cost-effectiveness ratios (ICERs) correctly. They reported the average cost per DFD and did not compare the incremental cost per additional DFD. For fingernails, terbinafine was a dominant strategy and provided higher effectiveness at lower costs than the other strategies. For toenails, ciclopirox provided lower effectiveness at lower costs than terbinafine. The correct approach would have been to compare terbinafine with ciclopirox and to identify the fact that ciclopirox is dominated by terbinafine only on the basis of the ICER (extended dominance). Care should therefore be taken when using the results of this analysis.
Implications of the study The authors suggested "pharmacoeconomic dominance provides pressing evidence for adopting terbinafine as the drug of choice for the treatment of onychomycosis".
Bibliographic details Casciano J, Amaya K, Doyle J, Arikian S, Shear N, Haspel M, Kahler K. Economic analysis of oral and topical therapies for onychomycosis of the toenails and fingernails. Managed Care 2003; 12(3): 47-54 Other publications of related interest Marchetti A, Piech CT, McGhan WF, Neugut AI, Smith BT. Pharmacoeconomic analysis of oral therapies for onychomycosis: a US model. Clinical Therapeutics 1996;18:757-77.
Gupta AK. Pharmacoeconomic analysis of ciclopirox nail lacquer solution 8% and the new oral antifungal agents used to treat dermatophyte toe onychomycosis in the United States. Journal of the American Academy of Dermatology 2000;43:S70-S80.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Antifungal Agents /classification /economics /therapeutic use; Cost-Benefit Analysis; Drug Costs /statistics & Economics, Pharmaceutical; Foot Dermatoses /drug therapy; Hand Dermatoses /drug therapy; Humans; Itraconazole /administration & Managed Care Programs /economics; Naphthalenes /economics /therapeutic use; Onychomycosis /drug therapy /economics; Pyridones /economics /therapeutic use; United States; dosage /economics /therapeutic use; numerical data AccessionNumber 22003006302 Date bibliographic record published 31/05/2005 Date abstract record published 31/05/2005 |
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