Cost-effectiveness analyses and cost analyses in castration-resistant prostate cancer: A systematic review.

BACKGROUND: Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias. METHODS: A systematic literature search was performed in the databases PubMed, CINAHL Complete, the Cochrane Library and Web of Science Core Collection for costs-effectiveness analyses, model-based economic evaluations, cost-of-illness analyses and budget impact analyses. Reported costs were inflated to 2015 US$ purchasing power parities. Quality assessment and risk of bias assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist and the Bias in Economic Evaluations checklist, respectively. RESULTS: In total, 38 articles were identified by the systematic literature search. The methodological quality of the included studies varied widely, and there was considerable risk of bias. The cost-effectiveness treatments for CRPC and mCRPC was assessed with incremental cost-effectiveness ratios ranging from dominance for mitoxantrone to $562,328 per quality-adjusted life year gained for sipuleucel-T compared with prednisone alone. Annual costs for the treatment of castration-resistant prostate cancer ranged from $3,067 to $77,725. CONCLUSION: The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality-adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations. High-quality cost-effectiveness analyses based on randomized controlled trials are needed in order to make informed decisions on the management of castration-resistant prostate cancer and the resulting financial impact on the healthcare system.

[The non-hormonal treatment of metastatic prostate cancer]. / Le traitement non hormonal de la maladie métastatique du cancer de la prostate.

AIM: To describe drugs used in the non-hormonal treatment of metastatic prostate cancer. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: The metabolic radiotherapy although under-used for this indication, kept a place at the beginning of the disease. Radium-223 chloride seems to have to occupy an important place in the coming years. The chemotherapy, the only recourse until very recently in the castration-resistant prostate cancer, must redefine its place partially. The denosumab provide an interesting alternative to bisphosphonates. CONCLUSION: The non-hormonal treatment of the metastatic disease of the prostate cancer is changing rapidly with the emergence of new molecules. Urologist must know perfectly these new drugs.

Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis.

Treatment options for secondary progressive multiple sclerosis (SPMS) are limited. Mitoxantrone is routinely used to stabilize disease progression; however, evolving evidence suggests clinical benefit from intensive treatment with autologous haematopoietic stem cell transplantation (HSCT). Given differences in cost and outcomes, preliminary cost-effectiveness studies are warranted if this approach is to be developed for more widespread application in SPMS. We developed a decision-analytic Markov model to explore the potential cost-effectiveness of autologous HSCT versus mitoxantrone in SPMS, using patient-level data from registry sources. The model evaluates the lifetime costs and health outcomes associated with disability progression and relapse. Sensitivity analyses were undertaken to examine the uncertainty surrounding cost-effectiveness outcomes. In the absence of randomised controlled trial (RCT) evidence, conditions for comparative analysis were not ideal. Under optimistic assumptions, HSCT is estimated to cost below pound3000 per quality adjusted life year gained. However, when a strict 6-month sustained progression rule is adopted, HSCT may be less effective and more expensive than mitoxantrone. The model results were sensitive to reducing procedural costs and HSCT-related mortality. We conclude that HSCT could potentially achieve an acceptable level of cost-effectiveness. However, caution should be exercised as large, high-quality RCTs comparing HSCT versus mitoxantrone are necessary to validate these findings.

Value of information and value of implementation: application of an analytic framework to inform resource allocation decisions in metastatic hormone-refractory prostate cancer.

OBJECTIVE: In a budget-constrained health-care system, decisions about investing in strategies to promote implementation have to be made alongside decisions about health-care provision and research funding. Using a Bayesian decision-theoretic approach, an analytic framework has been developed to inform these separate but related decisions, establishing the expected value of both perfect information (EVPI) and perfect implementation (EVPIM). We applied this framework to inform decision-making about resource allocation to metastatic hormone-refractory prostate cancer (mHRPC) in the UK. METHODS: Based on available evidence on the cost-effectiveness of all plausible treatments for mHRPC, we determined which treatment option(s) were cost-effective and explored the uncertainty surrounding this decision. Given the decision uncertainty and the variation in care provided by health-care professionals, we then determined the EVPI and EVPIM. Finally, we performed sensitivity analyses to explore the influence of alternative assumptions regarding various decision parameters on the efficiency of resource allocation. RESULTS: Depending on the cost-effectiveness threshold (lambda), we identified mitoxantrone plus prednisone/prednisolone and docetaxel plus prednisone/prednisolone (3 weekly) as the optimal treatments for mHRPC. Given current clinical practice, there appears to be considerable scope for improving the efficiency of health-care provision: the EVPI (estimated to be over pound13 million) indicates that acquiring further information could be cost-effective; and the EVPIM (estimated to be over pound4 million) suggests that investing in strategies to implement the treatments regimens being identified as optimal is potentially worthwhile. Through sensitivity analyses, we found that the EVPI and EVPIM are mainly driven by lambda, the number of treatment options being considered, the current level of implementation, and the size of the eligible patient population. CONCLUSION: The application demonstrates that the framework provides a simple and useful analytic tool for decision-makers to address resource allocation problems between health-care provision, further research, and implementation efforts.

Utilization, cost trends, and member cost-share for self-injectable multiple sclerosis drugs--pharmacy and medical benefit spending from 2004 through 2007.

BACKGROUND: In 1993, interferon beta-1b became the first of 4 self-injectable multiple sclerosis (MS) drugs to be approved by the U.S. Food and Drug Administration. Initially covered as a medical expense, self-injectable MS drugs are increasingly considered specialty pharmaceuticals and are often covered under the pharmacy benefit. Self-injectable MS drugs are expensive, costing approximately $2,000 per month per patient in 2007. OBJECTIVES: To (1) determine the trends for price and utilization of self-injectable MS drugs, (2) meld medical and pharmacy claims data to capture total health care spending on self-injectable MS drugs, and (3) calculate the out-of-pocket cost-share for members with pharmacy benefits. METHODS: A pharmacy benefits manager with integrated medical claims for approximately 1.8 million commercial members, about 20% of its total of 9 million commercial members, analyzed self-injectable MS pharmacy claims for a 45-month period beginning in January 2004 and ending in September 2007 and integrated medical and pharmacy claims for a 42-month period beginning in January 2004 and ending in June 2007. The 9 million members are beneficiaries of 10 Blue Cross Blue Shield (BCBS) health plans distributed throughout the United States, and the subset of 1.8 million members are enrolled in 1 BCBS health plan in the Northern Plains states. Self-injectable MS drugs were identified using Generic Product Identifier (GPI) codes for the National Drug Code (NDC) numbers on pharmacy claims. Mail order pharmacy claims with up to a 90-day supply were counted as 3 claims, and community pharmacy claims dispensed with up to a 34-day supply were counted as 1 claim. Self-injectable MS drugs were identified from medical claims using Healthcare Common Procedure Coding System (HCPCS) codes: J1595 for glatiramer, J1830 for subcutaneous interferon beta-1b, Q3026 for subcutaneous interferon beta-1a, and Q3025 and J1825 for intramuscular interferon beta-1a. RESULTS: For the approximately 9 million members with data from pharmacy claims only, these 4 self-injectable MS drugs accounted for approximately 1.8% of total pharmacy benefit spending in 2004, 1.9% in 2005, 2.3% in 2006, and 2.4% in 2007. The mean average wholesale price (AWP) per member per month (PMPM) increased by 56.8%, from $1.11 PMPM in the first quarter of 2004 to $1.74 PMPM in the third quarter of 2007. Utilization was flat at about 82-83 claims per 100,000 members per month during the 45-month measurement period. The average annual price increase per unit ranged from 8.9% for interferon beta-1a to 13.3% per year for interferon beta-1b. Members paid a median out-of-pocket cost per pharmacy claim of $15 in 2004, $20 in 2005 and 2006, and $25 in the first 9 months of 2007. For the 1.8 million members with both pharmacy and medical benefit claims, the medical benefit accounted for 2.5% of total spending on MS self-injectables in 2004, 2.0% in 2005 and 2006, and 1.2% in 2007. CONCLUSION: The percentage of all pharmacy expenditures that was attributable to self-injectable MS drugs increased from 1.8% in 2004 to 2.5% in 2007. Nearly all of the increase in spending on self-injectable MS drugs over the nearly 4-year period was attributable to drug price increases because PMPM utilization was essentially unchanged. The median member cost-share was approximately 1% of the total cost of self-injectable MS drugs.

Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis: a comparative study.

Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one or more EDSS points in the prior two years were selected to receive either cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4 years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2 years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS patients were treated for two years with clinical evaluation (relapse rate, disability progression) every three months and radiological imaging (conventional magnetic resonance imaging) before therapy initiation and at the end of the first and second years of therapy. Safety profile and costs of the two therapeutic protocols were also analysed. In terms of clinical and radiological measures the drugs exerted a quite identical effect on both, and produced a significant reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01). Subgroups of mitoxantrone- and cyclophosphamide-responding patients were identified (14/25 and 17/25, respectively) and were characterized by a significantly shorter duration of the secondary progressive phase of the disease. In these subgroups, the improvement in the EDSS score at the end of therapy was highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of both drugs were acceptable; however, the Cy-based therapy protocol was significantly less expensive. We conclude that Cy should be considered as a therapeutic option in rapidly deteriorating SPMS patients.

Radiotherapy is a cost-effective palliative treatment for patients with bone metastasis from prostate cancer.

BACKGROUND: To evaluate the various treatments for patients with hormone-refractory prostate cancer with bone metastases using a Markov model. METHODS AND MATERIALS: The base case to be evaluated was of a man with hormone-refractory prostate cancer. The evaluated palliative treatments were pain medication only, chemotherapy consisting of mitoxantrone and prednisone, and single- and multifraction radiotherapy (RT). A literature search was used to generate the transition probabilities and patient utilities. Modeling was used to generate the cost estimates. Expert opinion was used to generate utilities and cost estimates in the absence of literature data. Second-order Monte Carlo simulation produced incremental cost-effectiveness scatterplots and 95% confidence ellipses. RESULTS: Pain medication had the least expected mean cost of all the treatment options at 11,700 US dollars but also the second lowest quality-adjusted survival at 5.75 quality-adjusted life months. Chemotherapy had the highest expected mean cost, 15,300 US dollars, but the lowest quality-adjusted life months (4.93). Incremental cost-effectiveness analysis revealed that single-fraction RT was the most cost-effective treatment, with a cost of 6,857 US dollars/quality-adjusted life year; multifraction RT had an incremental cost-effectiveness ratio of 36,000 US dollars/quality-adjusted life year. Chemotherapy was dominated by pain medication. CONCLUSION: Within the limits of the established model, single-fraction RT was the most cost-effective palliative treatment compared with pain medication, chemotherapy, and multifraction RT. The use of this model allowed comparison of different treatment regimens that could never be evaluated together in a randomized clinical trial.

Health outcomes in multiple sclerosis.

PURPOSE OF REVIEW: Economic considerations are increasingly important in the evaluation of innovative medical technologies. In the past few years, evaluations of cost and cost-effectiveness analysis became a popular topic for multiple sclerosis research. Here, we review cost-of-illness and cost-utility studies in multiple sclerosis published during the past 2 years. RECENT FINDINGS: Despite differences in methodology, several cost-of-illness studies unequivocally demonstrated that indirect costs as a result of sick leave, premature retirement or loss of income made up almost half of the overall costs, and that total costs were higher in the more advanced stages of the disease. Cost-effectiveness studies of recombinant IFN-beta preparations demonstrated a marked variability in the incremental cost per quality-adjusted life-year, with amounts ranging from Euro 28 432 to US$338 738. For glatiramer acetate and mitoxantrone, only limited data are available, but even these few studies differed in their results. SUMMARY: Health outcome studies constitute a new and emerging field of multiple sclerosis research. All studies performed so far underscore the importance of indirect cost in multiple sclerosis. However, the marked differences in cost-effectiveness studies illustrate that the method of economic modeling has considerable impact on the results of these studies, which need standardization in order to evaluate properly the economic consequences of new and expensive therapies in multiple sclerosis.

A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis.

The approval by the FDA of four immunomodulators (three IFNs and glatiramer acetate) and one immunosuppressant (mitoxantrone; Novantrone) for the treatment of multiple sclerosis is definitely the most important progress in this field since the first description of the disease > 150 years ago. However, both types of immunotherapies raise specific problems. Immunomodulators benefit patients in the relapsing-remitting phase, or patients in the secondary-progressive phase showing clinical and/or radiological signs of active inflammatory processes. Their benefit is modest, but seems to persist with long-term administration, as their tolerance is acceptable. Mitoxantrone is a rescue therapy reserved to patients with an aggressive, rapidly progressive form of the disease. This immunosuppressant is effective on inflammatory processes and pathomechanisms responsible for disability progression. Unfortunately, its cardiotoxicity and potential leukaemogenicity prevent an administration beyond 2 or 3 years. Thus, there is a need to improve on the efficacy of immunomodulators and to reduce the toxicity of immunosuppressants. Combination therapies with immunomodulators and antioxidants or with neuroprotective drugs against excitotoxicity or Na + /Ca 2+ channellopathy are currently being investigated. With regard to immunosuppressants, the development of monoclonal antibodies with fully human protein sequences and the synthesis of a new molecule as effective as mitoxantrone but with a much lower toxicity (pixantrone) seem promising to halt or even to prevent disability progression.

Mitoxantrone: a review of its use in multiple sclerosis.

Mitoxantrone (Novantrone), a synthetic anthracenedione derivative, is an antineoplastic, immunomodulatory agent. Its presumed mechanism of action in patients with multiple sclerosis (MS) is via immunomodulatory mechanisms, although these remain to be fully elucidated. Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease. In a pivotal randomised, double-blind, multicentre trial, mitoxantrone 12 mg/m(2) administered once every 3 months for 2 years provided significant improvements in neurological disability ratings, including Kurtzke Expanded Disability Status Scale (EDSS), Ambulatory Index (AI) and Standardised Neurological Status (SNS) scores, compared with placebo. The drug also significantly reduced the mean number of corticosteroid-treated relapses and prolonged the time to the first treated relapse, with the beneficial effects on disease progression supported by magnetic resonance imaging. Post hoc analyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS. The drug was generally well tolerated in patients with MS. Adverse events were generally mild to moderate in severity and usually resolved upon discontinuation of treatment or with appropriate pharmacotherapy. At the recommended dosage, mitoxantrone appears to have a low potential to cause cardiotoxicity. In conclusion, intravenous mitoxantrone reduces the relapse rate and slows progression of the disease in patients with worsening RRMS, PRMS or SPMS; thus providing a new option for the management of these patients. The drug was generally well tolerated at the recommended dosage, although potential cardiotoxicity limits the total cumulative dose to 140 mg/m(2). Further studies are warranted to determine which patients with worsening RRMS, PRMS or SPMS are most likely to benefit from mitoxantrone treatment and to more fully define the long-term safety and tolerability of mitoxantrone, including the use of concomitant cardioprotectants to extend the therapeutic lifespan of the drug. Pharmacodynamic Profile. Mitoxantrone, a synthetic anthracenedione derivative, is an established cytotoxic, antineoplastic agent. Its presumed mechanism of action in multiple sclerosis (MS) is immunosuppression. In antineoplastic studies, the drug showed several immunomodulatory effects, inducing macrophage-mediated suppression of B-cell, T-helper and T-cytotoxic lymphocyte function. Currently, the pharmacodynamic properties of mitoxantrone have not been investigated to any extent in patients with MS. In one study, 6 months' treatment with intravenous mitoxantrone generally had no effect on the distribution of cytokine-positive peripheral blood monocyte cells in patients with MS. In an animal model of the disease, mitoxantrone suppressed the development and progression of both actively and passively induced acute experimental allergic encephalomyelitis (EAE). It appeared to be 10-20 times more effective than cyclophosphamide in the suppression of EAE. Moreover, mitoxantrone approximately doubled the mean time to onset of EAE versus control animals (279 vs 148 days after immunisation; p < 0.00005). In vitro, mitoxantrone 10 and 100 micro g/L inhibited myelin degradation by leucocytes and peritoneal macrophages derived from mice with acute EAE by approximately 60% and 100%. Pharmacokinetic Profile. Currently, there are no published pharmacokinetic data for intravenous mitoxantrone in pitoxantrone in patients with MS, paediatric patients or in those with renal impairment. All studies, to date, have been in patients with cancer receiving a single, approximately 30-minute intravenous infusion of mitoxantrone 5-14 mg/m(2). The drug exhibits triexponential pharmacokinetics, with a rapid initial distribution (alpha) phase, an intermediate distribution (beta) phase and a much slower elimination (gamma) phase. The mean half-life of the alpha phase appears to be 6-12 minutes and that of the beta phase 1.1-3.1 hours. Mitoxantrone has a high affinity for tissue, with a volume of distribution of up to 2248 L/m(2). Mitoxantrone persists for prolonged periods in tissues and was detectable in autopsy tissue from patients who last received the drug up to 272 days before death. At concentrations of 10-10000 ng/mL, the drug was 70-80 % bound to plasma proteins in dogs. Elimination of mitoxantrone occurs predominantly through biliary excretion and may be impaired in patients with hepatic dysfunction or third space abnormalities (e.g. ascites). The mean terminal elimination half-life of mitoxantrone ranged from 23 hours to 215 hours. Renal clearance accounts for 10 % of the total clearance of the drug. Total clearance of mitoxantrone ranged from 13 to 34.2 L/h/m(2) and renal clearance from 0.9 to 2.7 L/h/m(2). The drug appears to have a low potential for interaction with other concomitantly administered agents. Therapeutic Efficacy. Intravenous mitoxantrone (infusion of > or = 5 minutes), either as monotherapy or in combination with intravenous methylprednisolone, delayed the progression of the disease in patients with secondary-progressive (SP) or worsening relapsing-remitting (RR) MS (the latter is also termed progressive-relapsing MS) in comparative, randomised, multicentre trials. In a double-blind, monotherapy trial (Mitoxantrone In Multiple Sclerosis [MIMS] trial), mitoxantrone 12 mg/m(2) (n = 60) once every 3 months for 2 years significantly improved neurological disability relative to placebo (n = 64), as assessed by changes in mean Kurtzke Expanded Disability Status Scale (EDSS) score, mean Ambulatory Index (AI) score and mean Standardised Neurological Status (SNS) score. The drug also significantly reduced the mean number of corticosteroid-treated relapses per patient and prolonged the time to the first treated relapse. A Wei-Lachin multivariate analysis of these five efficacy variables indicated that the global difference between the two treatment groups was 0.30 (p < 0.0001). Mitroxantrone was also more effective than placebo according to secondary endpoints in this study, with fewer mitoxantrone recipients experiencing a relapse, a deterioration of > or =1 EDSS point or a confirmed deterioration in EDSS score over a 3-month period. Mitoxantrone recipients also showed less deterioration in quality-of-life ratings and had fewer hospital admissions, whereas more placebo recipients had new gadolinium-enhanced lesions at study end (the latter parameter was assessed using magnetic resonance imaging [MRI] in a subgroup of 110 patients, including 40 patients who received an exploratory 5 mg/m(2) dose). Furthermore, post hoc analyses indicated that the beneficial effects of mitoxantrone treatment on EDSS, SNS and AI scores were sustained for at least 12 months after cessation of treatment, with mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. Preliminary data from a cost-minimisation analysis based on results from the MIMS trial indicated that approximately half of the cost of mitoxantrone was offset by cost savings in other areas associated with the treatment of MS (direct and indirect major costs), with a total annual incremental cost for mitoxantrone of dollar 1661 per patient. Combination therapy once-monthly with intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g was more effective than intravenous methylprednisolone 1g once every month in preventing the development of gadolinium-enhanced lesions in patients with very active RRMS or SPMS (double-blind assessment using MRI scans). After 6 months, significantly more combination therapy recipients had no new gadolinium-enhanced lesions (90.5% vs 31.3% with monotherapy; p < 0.001) [primary endpoint]. There were also significant reductions in both the mean number of new enhancing lesions and the total number of gadolinium-enhanced lesions in patients receiving combination therapy versus methylprednisolone monotherapy.Tolerability. Mitoxantrone was generally well tolerated in patients with MS. Treatment-emergent adverse events occurring significantly more frequently with mitoxantrone (12 mg/m(2) once every 3 months for 2 years) than placebo were nausea, alopecia, menstrual disorders, urinary tract infection, amenorrhoea, leucopenia and elevated gamma-glutamyltranspeptidase levels. Adverse events were usually mild to moderate in severity and generally resolved with discontinuation of treatment or when treated with appropriate pharmacotherapy. Eight percent of patients discontinued treatment in the mitoxantrone 12 mg/m(2) group due to an adverse event versus 3% of placebo recipients. The incidence of drug-related acute myelogenous leukaemia was very low (0.12%) in a cohort of 802 patients with MS receiving mitoxantrone. Evidence suggests that the risk of cardiotoxicity is low in patients with MS. After 1 year of monotherapy, 3.4% of mitoxantrone recipients had a reduction in left ventricular ejection fraction (LVEF) to < or =50% compared with 0% of placebo recipients; at the end of the second year, respective incidences were 1.9% and 2.9% (total cumulative dose of mitoxantrone per patient was 96 mg/m(2) after 2 years' treatment). (ABSTRACT TRUNCATED)

A cost-utility analysis of mitoxantrone hydrochloride and interferon beta-1b in the treatment of patients with secondary progressive or progressive relapsing multiple sclerosis.

BACKGROUND: Information on the cost utility of interferon beta-1b and mitoxantrone hydrochloride, 2 disease-modifying agents approved by the US Food and Drug Administration for the treatment of secondary progressive (SP) multiple sclerosis (MS), is limited. OBJECTIVE: The aim of this study was to compare the cost utility of i.v. mitoxantrone hydrochloride administered every 3 months, s.c. interferon beta-1b administered every other day, and routine supportive care from the perspectives of both the insurer and society. METHODS: We used a Markov model with health states based on the Kurtzke Expanded Disability Status Scale (EDSS) scores from both an insurer's and a societal perspective (including direct and total costs, respectively). Theoretical patients entered the model with an EDSS score of 3; their progression was followed for 10 years. Transition probabilities were derived from clinical trial data. Cost and utility inputs were taken from the literature. Sensitivity analyses were conducted on all variables. RESULTS: From the insurer's perspective, the incremental cost-utility ratio of mitoxantrone hydrochloride therapy compared with routine supportive care was 58,272 dollars per quality-adjusted life year (QALY) gained. From a societal perspective, mitoxantrone hydrochloride was more effective and less costly than supportive care. From the perspectives of insurers and society, the cost-utility ratios of interferon beta-1b compared with routine supportive care were 338,738 dollars and 245,700 dollars per QALY gained, respectively. When compared with mitoxantrone hydrochloride, interferon beta-1b had an incremental cost-utility ratio of 741,331 dollars and 658,402 dollars per QALY from the insurer's and society's perspectives, respectively. Cost-utility ratios for mitoxantrone hydrochloride were sensitive to acquisition and administration costs of therapy and to effectiveness at slowing disease progression. Cost-utility ratios for interferon beta-1b were not sensitive to any of the variables included in the model. CONCLUSIONS: Mitoxantrone hydrochloride is likely to be a cost-effective treatment for patients with SPMS or progressive relapsing MS from an insurer' perspective and is cost saving from a societal perspective. Interferon beta-1b is not likely an efficient treatment using conventional comparisons for cost-effectiveness. This analysis has potentially important implications for policy implementation; however, decisions about which agent to use for each patient should consider the treatment's adverse-event profile, the method of administration, and the patient's preferences for these factors.

Cost-effectiveness analysis with risk aversion.

This paper discusses why, in a medical context, the standard assumption of a risk-neutral social planner is inappropriate and develops a framework for conducting cost-effectiveness (CE) analysis when social planners are risk-averse. This framework demonstrates that if new medical interventions are variance increasing (decreasing), the risk-neutral approach will approve (reject) projects that should be rejected (accepted). This methodology is applied to two medical interventions that have been previously evaluated and considered cost-effective in the published literature. Since both conclusions assumed risk neutrality we determine the level of societal risk-aversion that would be necessary to reject these new interventions and compare these levels to previous estimates of risk-aversion in the economics literature. We find that for reasonable values of the risk-aversion parameter, only one of the two interventions should be approved. It is our recommendation that the cut-off risk aversion parameter (the level of risk-aversion above which a project would be rejected) should become a standard reported figure in future CE studies.

Cost of de novo acute myeloid leukemia induction therapy in adults: analysis of EORTC-GIMEMA AML10 and FLANG regimens.

Since the social and financial impact of AML therapy is becoming more and more relevant we analyzed the cost of induction therapy of two different regimens. The first one is part of the widely employed EORTC-GIMEMA AML-10 and consists often days of therapy. The second (FLANG) is a short (three day), Fludarabine, Ara-C, mitoxantrone and G-CSF containing regimen. We first retrospectively analyzed the outcome of 77 consecutive AML patients with comparable clinical and haematological features receiving FLANG (25) or AML-10 (52), between June 1993 and October 1999, and observed equivalent CR rate, as well as DFS and overall survival duration. We then selected 9 non pretreated patients per group who reached CR after one course of therapy. Patients treated with FLANG had a statistically significant earlier platelet recovery compared to those treated with AML-10, fewer days of intravenous antibiotic therapy (14/22, respectively, p < 0.05), and a shorter hospitalization period (22/33 days, p < 0.01). FLANG was significantly more expensive than AML 10 as far as the cost of antiblastic drugs (p < 0.01) and G-CSF support (p < 0.05) are concerned. On the contrary, the expense for antiemetic drugs (p < 0.01) and the cost of personnel and other services ($5,906/$3,970, p < 0.05) were higher for AML-10 than for FLANG. Overall, the average costs of FLANG and AML10 were $9,269 and $12,424 respectively (p < 0.05; difference = -25%). Our study seems to indicate that, compared to AML-10, FLANG induction is as effective, less expensive and it allows for a decrease in the length of hospitalization and thus for better exploitation of the financial resources of Hematology-Oncology departments.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Chemotherapy waste reduction through shelf-life extension.

Minimization of total drug expenditures within the health care system, without affecting patient outcome has become a rational goal in today's economic, environment. The objective of this study was to observe the effect of extending the shelf-life for three chemotherapy medications, [doxorubicin, epirubicin and mitoxantrone] on wastage of these medications. Prior to and following the introduction of new, longer, shelf-lives for these three medications, prospective, non-randomized, unblinded four-month chemotherapy wastage audits for all chemotherapy medications were completed at 18 institutional sites within Ontario (six Ontario Cancer Treatment and Research Foundation clinics, ten Ontario hospitals and two preparation sites in a large cancer treatment centre). Data were provided by 18 sites in 1989 but from only 12 sites in 1990. Ten of the 12 sites extended their shelf-lives for each of doxorubicin, epirubicin and mitoxantrone, and on average, waste at these sites was reduced to less than 1% of the 1989 total for epirubicin, less than 15% for doxorubicin and 35% for mitoxantrone. Many sites eliminated waste entirely for these drugs. For sites which did not extend their shelf-lives, the waste remained unchanged. We conclude that appropriate extension of the shelf-life for chemotherapy medications can reduce waste, and is a relatively simple method of reducing expenditures without affecting health outcomes or adding additional complications to IV chemotherapy.

Cost of complete remission induction in acute myeloblastic leukemia: evaluation of the cost-effectiveness of a new drug.

The use of new drugs in the treatment of AML could dramatically increase the cost of induction chemotherapy. To evaluate the cost-effectiveness of such new drugs, the overall cost to achieve complete remission (CR) with treatments including these drugs has to be compared to the cost of the daunorubicin-cytosine arabinoside (DNR-AraC) association, considered as the reference treatment. A retrospective analysis of charts from 15 patients treated with DNR-AraC was used to identify 228 items of cost, including general cost, diagnostic, supportive care, and chemotherapy. Eleven patients underwent CR after one course of chemotherapy for a cost of US$16,701 +/- 4451, and four patients achieved CR after two courses for a cost of US$37,130 +/- 4923. The chemotherapy represented only 1.4% of the total cost, supportive care 25% and general cost 56%. According to these data, the projective cost of a treatment with mitoxantrone instead of DNR was simulated in 40 untreated patients with AML. The better rate of CR obtained after one course of chemotherapy leads to a saving of 9% (US$1261) per patient, despite the higher cost of chemotherapy. Cost-effectiveness evaluation should be included in the clinical study of trials with new drugs.