Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia

In two major clinical trials, voriconazole and caspofungin were recommended as alternatives to liposomal amphotericin B for empirical use in febrile neutropenia. This study investigated the health economic impact of using voriconazole vs. caspofungin in patients with febrile neutropenia. A decision analytic model was developed to measure downstream consequences of empirical antifungal therapy. Clinical outcomes measured were success, breakthrough infection, persistent base-line infection, persistent fever, premature discontinuation and death. Treatment transition probabilities and patterns were directly derived from data in two relevant randomised controlled trials. Resource use was estimated using an expert clinical panel. Cost inputs were obtained from latest Australian sources. The analysis adopted the perspective of the Australian hospital system. The use of caspofungin led to a lower expected mean cost per patient than voriconazole (AU$40,558 vs. AU$41,356), with a net cost saving of AU$798 (1.9%) per patient. Results were most sensitive to the duration of therapy and the alternative therapy used post-discontinuation. In uncertainty analysis, the cost associated with caspofungin is less than that with voriconazole in 65.5% of cases. This is the first economic evaluation of voriconazole vs. caspofungin for empirical therapy. Caspofungin appears to have a higher probability of having cost-savings than voriconazole for empirical therapy. The difference between the two medications does not seem to be statistically significant however.     

Pharmacoeconomic assessment of therapy for invasive aspergillosis

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised hosts. Economic expenditures prompted by this invasive fungal infection (IFI) are significant. Although, the duration and associated costs of hospitalization comprise the largest proportion of costs in large surveillance studies, the newer oral antifungal agents may impact significantly on these costs. A review of the pharmacoeconomic (PE) studies is provided focussing on primary therapy, salvage therapy, empiric therapy and prophylaxis for IA. PE evaluations have demonstrated the cost effectiveness and dominance of voriconazole for targeted primary treatment of IA compared with other available agents. Differences in the drug choice and analytic methodology of the PE analyses of empiric antifungal strategy hamper definitive conclusions about the agents employed as empiric antifungal that may be directed at suspected IA although both caspofungin and voriconazole appear to be cost effective and dominant over liposomal amphotericin B (LAmB), whereas LAmB is more costly than conventional amphotericin B. Posaconazole is the most cost‐effective agent for antifungal prophylaxis against IFI and IA.     

Cost‐effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey

Anidulafungin has been shown to be non‐inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost‐effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life‐years, with an incremental cost‐effectiveness ratio of TL 15 410 (USD 4118) per life‐years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost‐effective therapy in treating IC from the Turkish hospital perspective.     

Pegfilgrastim Versus Filgrastim for Primary Prophylaxis of Febrile Neutropenia in Patients with non-Hodgkin’s Lymphoma: A Cost-Effectiveness Study

Aim: One method to deal with febrile neutropenia is the use of granulocyte colony stimulating factors (G-CSFs). Pegfilgrastim or Filgrastim injection can lead to a reduction in febrile neutropenia and severe neutropenia in patients receiving chemotherapy. This study aimed to compare the cost-effectiveness of using Pegfilgrastim, 3-day Filgrastim and 1-day Filgrastim medication strategies for the primary prophylaxis of febrile neutropenia in patients with relapsed non-Hodgkin’s lymphoma after salvage chemotherapy who referred to two referral centers affiliated to Iran, Shiraz University of Medical Sciences in 2014. Method: This cost-effectiveness study was conducted on 131 patients with non-Hodgkin’s lymphoma. The outcome of the study was the prevention of febrile neutropenia. The cost data were collected from the health payer’s perspective for each medication strategy by reviewing the patients’ medical records and using expert opinion. The results were presented in terms of the incremental cost-effectiveness ratio (ICER) and the sensitivity analysis was used to assess the robustness of results. In this study, the collected data were analyzed using Excel 2007 and Tree-age 2011. Results: The results showed that the degrees of febrile neutropenia prevented by Pegfilgrastim, 3-day Filgrastim and 1-day Filgrastim strategies were 0.97, 0.95 and 0.83, respectively, and the average annual costs of hospitalization per patient were, 5299, 4959 and 5808 PPP$. Conclusion: The results showed that while 1-day Filgrastim was absolutely predominant, using the 3-day Filgrastim and Pegfilgrastim strategies were more cost-effective. Therefore, they can be recommended respectively as the first and second treatment priorities in patients with non-Hodgkin’s lymphoma after salvage chemotherapy.     

A rescue therapy with a combination of caspofungin and liposomal amphotericin B or voriconazole in children with haematological malignancy and refractory invasive fungal infections

Combination treatment of paediatric invasive fungal infections (IFIs) has rarely been reported. A total of 17 children with 19 IFI episodes were enrolled in the study. The median age of the patients was 5.3 (range 0.5–17) years. IFI was classified as proven in 4, probable in 12 and possible in 3 episodes. These patients received empiric antifungal treatment, which consisted of liposomal amphotericin B (LAmB) monotherapy for a median duration of 12 days (range 3–69 days). All patients were refractory to LAmB; therefore, caspofungin was added to the therapy in 11 patients. In the remaining six patients, LAmB was ceased and a combination of caspofungin and voriconazole was started. Among the patients who received caspofungin + LAmB, four did not show favourable response and the combination was switched to caspofungin + voriconazole. The median (range) and total duration of the therapy were 7 (3–14) days and 91 patient days for LAmB + caspofungin combination and 49 (7–126) days and 516 patient days for caspofungin + voriconazole combination. We found a favourable response rate of 68.4% in 16 proven or probable IFI episodes. Twelve‐week survival rate of these patients was 75%. No serious side effect was observed among the patients. Our data suggest that combination antifungal therapy is safe and effective in children with haematological malignancies.     

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI‐associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost‐effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision‐analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost‐effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost‐effective than posaconazole regarding cost per additional IFI and additional death avoided.     

Modern antifungal therapy for neutropenic fever

Empirical antifungal therapy has been shown to decrease the number of documented fungal infections in the setting of persistent fever during neutropenia. For decades, amphotericin B deoxycholate has been considered the agent of choice for first-line therapy in this setting. New antifungal agents associated with less toxicity, including the lipid formulations of amphotericin, voriconazole, and caspofungin, are now available and are considered to be suitable alternative first-line agents. In order to ensure appropriate therapy, however, the clinician must consider not only the differences between these antifungals but also patient-specific factors before initiating treatment.     

Disseminated mucormycosis associated with invasive pulmonary aspergillosis in a patient treated for post-transplant high-grade non-Hodgkin's lymphoma

The incidence of mucormycosis, defined as systemic infection caused by fungi of the class Phycomycetes has been increasing over the past 2 decades, especially in profoundly immunocompromised hosts. We report a new case in a patient presenting with post-transplant high-grade non-Hodgkin's lymphoma who received a prolonged treatment with voriconazole and caspofungin for an invasive pulmonary aspergillosis. Definite diagnosis of mucormycosis was made by liver biopsy of nodules mimicking progressive lymphoma. The patient died 1 week after the diagnosis of mucormycosis despite the administration of liposomal amphotericin B. The role of voriconazole and caspofungin in the emergence of mucormycosis is discussed.     

First isolation of Candida wangnamkhiaoensis from the blood of immunocompromised paediatric patient

Candida wangnamkhiaoensis is a species clustered under the Hyphopichia clade has not ever been isolated from any clinical specimens. To the best of our knowledge, this is the first report of C. wangnamkhiaoensis associated with fungaemia in immunocompromised paediatric patient. The isolate was assigned a strain name as UZ1679/14, in which the identification was confirmed by a polymerase chain reaction‐sequencing of the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rRNA gene. Antifungal susceptibility pattern showed that the isolate was sensitive to anidulafungin, caspofungin, fluconazole and voriconazole. The patient clinically improved after the antifungal treatment with caspofungin.     

Fatal Blastoschizomyces capitatus sepsis in a neutropenic patient with acute myeloid leukemia: first documented case from Greece

Blastoschizomyces capitatus (formerly known as Geotrichum capitatum and Trichosporon capitatum) is a rare, yet an emerging, cause of invasive infections in immunosuppressed patients. Profound and prolonged neutropenia is the crucial predisposing factor for this yeast infection. Blastoschizomyces capitatus was isolated from peripheral blood cultures of a profoundly neutropenic patient with acute myeloid leukemia (M2 FAB). Despite administration of antifungal chemotherapy with liposomal amphotericin B at 4.5 mg kg(-1) daily, the patient succumbed 4 days after initiation of treatment. Infections attributed to B. capitatus have generally a poor prognosis, although the yeast shows in vitro susceptibility to antifungal agents. Low flucytosine, caspofungin acetate, voriconazole and amphotericin B minimum inhibitory concentration values were also recorded with our isolate. The clinical relevance of the in vitro susceptibility testing against the isolate and the current antifungal chemotherapy regimens against B. capitatus systemic infections are discussed.     

Risk factors associated with complications in patients with chemotherapy‐induced febrile neutropenia in emergency department

Febrile neutropenia caused by chemotherapy is a frequent medical emergency associated with severe complications in the emergency department (ED). Timely administration of antibiotics is believed to improve patient outcomes for several infectious diseases such as pneumonia and sepsis but has not been thoroughly evaluated for reducing risk of complications in chemotherapy‐induced febrile neutropenia. The aim of this study was to evaluate associations between the risk factors and serious complications in patients presenting to the ED with febrile neutropenia. We reviewed the health information system database to identify a retrospective cohort of patients with febrile neutropenia who visited the ED of a tertiary medical hospital from January to December 2008. Only episodes of febrile neutropenia caused by chemotherapy for underlying cancer were included. Serious complications during hospitalization were defined as unstable hemodynamic status, respiratory distress, altered mental status, newly developed arrhythmia that required intervention, and death during hospitalization. Univariate and multivariate logistic regression analysis was performed to determine potential factors associated with serious complications. We further use decision tree approach to help analyze variables. Among a total of 81 febrile neutropenic episodes in 78 patients, 25 (30.8%) episodes of serious complications were identified. Latency of the first dose of antibiotics, pneumonia and platelet counts ≤ 50,000/mm³ were identified as independent factors associated with serious complications of febrile neutropenia. Earlier administration of antibiotics is associated with fewer complications in patients presenting to the ED with febrile neutropenia. Copyright © 2013 John Wiley & Sons, Ltd.     

Monitoring trough voriconazole plasma concentrations in haematological patients: real life multicentre experience

The objective of this retrospective study was to evaluate results from voriconazole therapeutic drug monitoring (TDM) in haematological patients in routine clinical practice. Between 2005 and 2010, 1228 blood samples were obtained from 264 haematological patients (median 3 samples/patient; range 1–27) receiving voriconazole for targeted/preemptive treatment of invasive aspergillosis (IA) (46.3% of samples), empirical therapy (12.9%) or prophylaxis (40.8%). A high‐pressure liquid chromatography assay was used to analyse voriconazole concentrations. Clinical and laboratory data were analysed retrospectively. The median of the detected voriconazole plasma concentration was 1.00 μg ml^?1 (range <0.20–13.47 μg ml^?1). Significant inter‐ and intra‐patients variability of measured concentrations (81.9% and 50.5%) were identified. With the exception of omeprazole administration, there was no relevant relationship between measured voriconazole concentrations and drug dose, route administration, age, gender, CYP2C19*2 genotype, gastrointestinal tract abnormality, administration via nasogastric tube, serum creatinine, and liver enzymes. However, per patient analysis identified significant role of individual voriconazole dose and drug form change on measured plasma concentration. Measured voriconazole concentrations did not correlate with the treatment outcome of patients with IA. We only identified a limited number of adverse events related to voriconazole therapy; however, the median plasma concentration was not different from concentrations measured in samples without reported toxicity. Our retrospective study has suggested that routine monitoring of voriconazole plasma concentrations has probably only a limited role in daily haematological practice.     

Cost‐effectiveness of amphotericin B formulations in the treatment of systemic fungal infections

Amphotericin formulations, indicated for invasive fungal infections (IFIs), vary in effectiveness, safety and costs. In Brazil, only the conventional formulation is provided by the Public Health System. The aim of this study was to perform a cost‐effectiveness analysis comparing conventional amphotericin B (CAB), liposomal amphotericin B (LAB) and amphotericin B lipid complex (ABLC). Therefore, a decision tree was developed. The model began with high‐risking patients on suspicion or confirmation of IFI. The analysis was conducted under the perspective of the Brazilian Public Health System. Model health states were defined according to medication use and clinical evolution. Clinical efficacy (cure) and transition probabilities were derived from the literature. Resource use was estimated from Brazilian data. Time horizon followed the maximum treatment time determined in the patient information leaflets (3 or 6 weeks). One‐way and probabilistic‐sensitivity analyses were conducted. The conventional formulation was the most cost‐effective. No dominance was observed; however, high incremental cost‐effectiveness ratios were obtained for LAB (USD 313 130) and ABLC (USD 1 711 280). Sensitivity analyses demonstrated the robustness of the results. CAB is the most cost‐effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large‐scale use in Brazil.     

Nuclear medicine imaging of infection in cancer patients (with emphasis on FDG-PET)

Infections are a common cause of death and an even more common cause of morbidity in cancer patients. Timely and adequate diagnosis of infection is very important. This article provides clinicians as well as nuclear medicine specialists with a concise summary of the most important and widely available nuclear medicine imaging techniques for infectious and inflammatory diseases in cancer patients with an emphasis on fluorodeoxyglucose positron emission tomography (FDG‐PET). ⁶⁷Ga‐citrate has many unfavorable characteristics, and the development of newer radiopharmaceuticals has resulted in the replacement of ⁶⁷Ga‐citrate scintigraphy by scintigraphy with labeled leukocytes or FDG‐PET for the majority of conditions. The sensitivity of labeled leukocyte scintigraphy in non‐neutropenic cancer patients is comparable with that in patients without malignancy. The specificity, however, is lower because of the uptake of labeled leukocytes in many primary tumors and metastases, most probably as a result of their inflammatory component. In addition, labeled leukocyte scintigraphy cannot be used for febrile neutropenia because of the inability to harvest sufficient peripheral leukocytes for in vitro labeling. FDG‐PET has several advantages over these conventional scintigraphic techniques. FDG‐PET has shown its usefulness in diagnosing septic thrombophlebitis in cancer patients. It has also been shown that imaging of infectious processes using FDG‐PET is possible in patients with severe neutropenia. Although larger prospective studies examining the value of FDG‐PET in cancer patients suspected of infection, especially in those with febrile neutropenia, are needed, FDG‐PET appears to be the most promising scintigraphic technique for the diagnosis of infection in this patient group.     

The economics of febrile neutropenia: implications for the use of colony-stimulating factors

The occurrence of fever and neutropenia following cancer chemotherapy generally prompts hospitalisation for evaluation and treatment. Colony-stimulating factors (CSFs) have been shown to reduce the risk of febrile neutropenia (FN) and the need for hospitalisation in such patients. This study was undertaken to obtain estimates of the actual institutional costs associated with FN and the impact of these costs on threshold estimates for the appropriate use of CSFs. Total hospital expenditures for patients admitted with FN over a 2 year period were studied. A cost allocation function was utilised to allocate all direct costs for non-revenue-generating support centres to revenue-generating service centres as indirect costs. A cost accounting function was then utilised to allocate direct and indirect costs for each service centre to the charge code level. Two groups of patients were defined based on diagnostic codes to represent the spectrum of patients with FN. Total hospital costs were estimated and incorporated into a cost model for the use of CSFs. Variation in the total cost of hospitalisation for FN relates primarily to differences in the average length of stay. The daily cost of hospitalisation was comparable in the groups studied, averaging between US$1675 and US$1892. Incorporation of these cost estimates into the cost model yielded FN risk threshold projections for CSF use in the range of 20-25%. Preliminary studies suggest that incorporation of non-medical, indirect and intangible costs into the CSF decision models will further decrease FN risk threshold projections. Total hospitalisation cost estimates for managing patients with FN are greater than those previously reported, reducing projected FN risk thresholds for CSF use.     

Clinical evidence for caspofungin monotherapy in the first‐line and salvage therapy of invasive Aspergillus infections

In 2001, caspofungin received market authorisation by the FDA and EMA and is globally licensed for several indications, including candidiasis, empirical antifungal therapy in patients with neutropenic fever of unknown origin and treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B or itraconazole. Despite the lack of phase III data in first‐line treatment of invasive aspergillosis, increasing evidence supports the use of first‐line therapy. Here, we analyse the evidence of therapeutic activity, represented by favourable response rates, of caspofungin for invasive aspergillosis. A systematic literature search was conducted to identify international presentations and papers reporting monotherapy with caspofungin. Efficacy data are summarised separately for first‐line and salvage therapy. Thirty‐one papers and published abstracts reported caspofungin therapy for aspergillosis. Fifteen full papers and two abstracts fulfilled the criteria of reporting significant outcome data for caspofungin monotherapy for invasive aspergillosis. Consistent with other analyses and the known safety profile, few adverse events and associated terminations of caspofungin medication have been reported. Although a randomised, comparative, prospective study using caspofungin in this indication is still lacking, growing evidence supports the efficacy of this echinocandin not only for salvage but also for first‐line therapy.     

Invasive infections due to Saprochaete and Geotrichum species: Report of 23 cases from the FungiScope Registry

Saprochaete and Geotrichum spp. are rare emerging fungi causing invasive fungal diseases in immunosuppressed patients and scarce evidence is available for treatment decisions. Among 505 cases of rare IFD from the FungiScope^? registry, we identified 23 cases of invasive infections caused by these fungi reported from 10 countries over a 12‐year period. All cases were adults and previous chemotherapy with associated neutropenia was the most common co‐morbidity. Fungaemia was confirmed in 14 (61%) cases and deep organ involvement included lungs, liver, spleen, central nervous system and kidneys. Fungi were S. capitata (n=14), S. clavata (n=5), G. candidum (n=2) and Geotrichum spp. (n=2). Susceptibility was tested in 16 (70%) isolates. All S. capitata and S. clavata isolates with the exception of one S. capitata (MIC 4 mg/L) isolate had MICs>32 mg/L for caspofungin. For micafungin and anidulafungin, MICs varied between 0.25 and >32 mg/L. One case was diagnosed postmortem, 22 patients received targeted treatment, with voriconazole as the most frequent first line drug. Overall mortality was 65% (n=15). Initial echinocandin treatment was associated with worse outcome at day 30 when compared to treatment with other antifungals (amphotericin B ± flucytosine, voriconazole, fluconazole and itraconazole) (P=.036). Echinocandins are not an option for these infections.     

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.     

Early hospital discharge followed by outpatient management versus continued hospitalization of children with cancer, fever, and neutropenia at low risk for invasive bacterial infection.

PURPOSE: To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI). PATIENTS AND METHODS: Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires. RESULTS: A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US 638 dollars (95% CI, 572 dollars to 703 dollars) and US 903 dollars (95% CI, 781 dollars to 1,025 dollars) for the ambulatory and hospital-based groups, respectively (P =.003). CONCLUSION: For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.     

Cost-effectiveness of interferon in chronic myeloid leukaemia: Analysis of four clinical studies

Background: Analysis of published survival curves can be used as the basis for incremental cost-effectiveness analyses in which two treatments are compared with one another in terms of cost per life-year saved. In patients with chronic myeloid leukaemia in chronic phase, long-term treatment with -interferon has been reported to improve survival in comparison with standard treatments with cytotoxic drugs. To assess the pharmacoeconomic profile of interferon treatment in terms of cost per life-year gained, we conducted an incremental cost-effectiveness analysis.Patients and methods: The clinical material utilised in our analysis derived from four published randomised trials comparing interferon vs. busulphan or hydroxyurea. The Gompertz model was used to estimate the total lifetime values of patient-years of subjects receiving interferon in comparison with subjects given a standard cytotoxic treatment.Results: Our primary analysis showed that maintenance treatment with interferon improved survival expectancy by 37 to 93 discounted years for every 100 patients. The incremental cost-effectiveness ratio of interferon vs. cytotoxic therapy ranged from $93,000 to $226,000 per life-year gained (discounted costs per discounted years). A secondary analysis showed that the dose of interferon had significant influence on the cost-effectiveness ratio. Because our literature search identified a fifth study that showed an extremely favourable outcome using interferon but that was not included in our primary analysis due to its design, we conducted another secondary analysis based on these five studies that, however, confirmed the results of the primary analysis.Conclusions: Our study indicates that an unselected long-term treatment with interferon implies an unfavourable cost effectiveness ranking in comparison with data of cost per life-year gained which had previously been obtained from other types of medical intervention.