Incremental Cost Utility Research Articles

Analisi costo-utilità del trattamento con atomoxetina e metilfenidato nei bambini con disturbi da deficit di attenzione con iperattività (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is a genetically based neurobiological disorder of children/adolescents, characterised by hyperactivity, impulsivity and difficulties in sustaining attention. Treatment of ADHD includes pharmacological interventions, counseling and parent training (multimodal treatment). In 2007 the Italian drug regulatory agency (AIFA) admitted two drugs for treatment of ADHD, i.e. methylphenidate, a stimulant that has been prescribed for a long time in the USA, and atomoxetine, a new non-stimulant drug, whose clinical effects will be reported in a national register. To estimate and compare treatment costs and quality of life over 12 months in the perspective of the Italian National Health Service. A review of published articles was performed in order to obtain data on effectiveness and QALYs gained for the two drugs. According to literature, effectiveness is defined as a post-treatment children’s response rate, measured as a >40% reduction on the ADHD Rating Scale. QALYs gained by the two drugs have been elicited from an English survey. Children with anxiety disorders, not treatable with methylphenidate, were included in the analysis. The model considers the differential response rates of the two drugs and the alternative treatment options, either for non-responders (switch to the second drug or no medication) and for patients with anxiety problems (use of atomoxetine, no medication). Only cost of drugs are included, the other psychological services being supposed equal for both treatment groups. From the meta-analysis response rates of 58.5% for atomoxetine and 66.6% for methylphenidate (44.9% after excluding children with anxiety disorders) were calculated. The average QALY associated with atomoxetine was 0.948 and with methylphenidate 0.915. In the base hypothesis the incremental cost per QALY for atomoxetine was €24,231, while in the no medication hypothesis €19,226. The sensitivity analysis showed a range of incremental costs per QALY between €18,122 and €25,427. The incremental cost utility ratios resulting from this study are consistent with other studies and are well below the threshold commonly accepted at international level, reflecting the willingness to pay of a public health service.

The Value-Based Medicine Comparative Effectiveness and Cost-Effectiveness of Penetrating Keratoplasty for Keratoconus

To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. Penetrating keratoplasty for patients with severe keratoconus seems to be a comparatively effective and cost-effective procedure when compared with other interventions across different medical specialties.

Cost-utility of a visiting service for older widowed individuals: Randomised trial

BackgroundDespite a growing understanding of the effectiveness of bereavement interventions and the groups that benefit most from them, we know little about the cost-effectiveness of bereavement interventions.MethodsWe conducted a cost-utility analysis alongside a randomized clinical trial on a visiting service for older widowed individuals (n = 110) versus care as usual (CAU; n = 106). The visiting service is a selective bereavement intervention that offers social support to lonely widows and widowers by a trained volunteer. Participants were contacted 6–9 months post-loss. Eleven percent of all contacted persons responded and eight percent participated in the trial. The primary outcome measure was quality adjusted life years (QALYs) gained (assessed with the EQ-5D), which is a generic measure of health status. Costs were calculated from a societal perspective excluding costs arising from productivity losses. Using the bootstrap method, we obtained the incremental cost utility ratio (ICUR), projected these on a cost-utility plane and presented as an acceptability curve.ResultsOverall, the experimental group demonstrated slightly better results against slightly higher costs. Whether the visiting service is acceptable depends on the willingness to pay: at a willingness to pay equal to zero per QALY gained, the visiting service has a probability of 31% of being acceptable; beyond €20,000, the visiting service has a probability of 70% of being more acceptable than CAU.ConclusionSelective bereavement interventions like the visiting service will not produce large benefits from the health economic point of view, when targeted towards the entire population of all widowed individuals. We recommend that in depth analyses are conducted to identify who benefits most from this kind of interventions, and in what subgroups the incremental cost-utility is best. In the future bereavement interventions are then best directed to these groups.Trial registrationControlled trials ISRCTN17508307

Cost effectiveness of self monitoring of blood glucose in patients with non-insulin treated type 2 diabetes: economic evaluation of data from the DiGEM trial

Objective To assess the cost effectiveness of self monitoring of blood glucose alone or with additional training in incorporating the results into self care, in addition to standardised usual care...

A Cost-Utility Analysis of Nilotinib for CML Patients Who Have Become Resistant to Imatinib.

Background: New generation BCR-ABL tyrosine kinase inhibitors are promising treatments for CML patients who are imatinib resistant or intolerant. The objective of this study was to consider the cost-utility of nilotinib in comparison to ‘high dose' (800 mg) imatinib (the current standard comparator in the UK) for chronic-phase CML patients resistant to standard dose 400 mg imatinib using a lifetime horizon. The analysis is based on a UK NHS perspective.Methods: A Markov model was developed using interim data from the phase II CAMN107A2101 registration study of nilotinib and data from the 39 patients who were dose-escalated, due to a sub-optimal response, to 800 mg imatinib within the IRIS phase III trial of imatinib versus interferon. Based on this evidence, the estimated 18-month survival has been extrapolated over a lifetime using parametric Weibull regression. Since the price of nilotinib in the UK was still to be determined at the time of preparation, the cost was assumed to be £106.94 per day, price parity with high dose imatinib. The costs and utilities associated with adverse events have been incorporated during the first six months following treatment. All costs and utilities were discounted at 3.5%.Results: Nilotinib is estimated to cost an additional £49K and generate an additional 2.18 Quality-Adjusted Life Year's (QALYs) in comparison to high dose imatinib over a patient's lifetime. Therefore, the incremental cost-utility of nilotinib versus high dose imatinib is expected to be approximately £22K per QALY gained. This result is subject to uncertainty around data extrapolation. However availability of longer term data from the ongoing nilotinib trial will allow validation at a later date.Conclusions: Our analysis suggests that nilotinib provides a clinically and cost-effective treatment (according to conventionally acceptable thresholds) for CML patients who have become imatinib resistant, in an indication where limited alternative treatment options exist.

Economic evaluation of treatment with orlistat in Italian obese patients

ABSTRACTThe XENDOS study showed that behavioural and pharmacological therapy can decrease the risk of metabolic disorders in obese patients.Methods: A probabilistic Bayesian Markov model simulating the outcomes of orlistat treatment on the obese Italian population has been developed with the WinBUGS software. The model integrates an algorithm to estimate cardiovascular risk based on Framingham Heart Study equations. Analyses adopted the societal cost perspective, including direct medical costs borne by both the National Health Service and the patient, since orlistat is not included in the Italian reimbursement list.Results: The simulation on the Italian obese population estimated an average increase in quality-adjusted life expectancy, a reduction of cardiovascular events and new diabetes cases. The average incremental cost–utility ratio is €75.3 (7.6–180.6) × 1000/QALY. The subgroup analysis showed that the benefits are relatively greater in older patients and in patients with impaired glucose tolerance (IGT). Two hypotheses have been explored to estimate the impact of a potential reimbursement decision by the Italian NHS: (1) orlistat is given to every obese patient; (2) orlistat is given only to obese IGT patients with a previous glucose tolerance general screening program to assess their eligibility. The cost utility of the strategies are €42.3 (−22.16–108.7) and €10.16 (−60.4–38.76) × 1000/QALY, respectively.Conclusion: Orlistat shows a good pharmacoeconomic profile and, in particular, the strategy of a screening programme to identify and treat the IGT subgroup has a cost–utility value of about €10 000/QALY. This value is lower than that of several therapeutic strategies commonly accepted and reimbursed in developed countries.

Four‐Year Cost‐Utility Analyses of Sealed and Nonsealed First Permanent Molars in Iowa Medicaid‐Enrolled Children

Dental sealants, by their ability to prevent caries and maintain teeth in better health, have some inherent utility to individuals, programs, or society. This study assessed the 4-year incremental cost utility of sealing first permanent molars of 6-year-old Iowa Medicaid enrollees from a societal perspective and identified the group of teeth or children in whom sealants are most cost effective. Dental services for first permanent molars were assessed using claims and encounter data for a group of continuously enrolled Medicaid enrollees who turned 6 between 1996 and 1999. Previously published utilities were used to weight the different health states. The weighted sum of outcomes [Quality-Adjusted Tooth-Years (QATYs)] was the measure of effectiveness. Costs and QATYs were discounted to the time of the child's sixth birthday. For all first molars, the cost of treatment associated with sealed teeth was higher but the utility was also slightly higher over the 4-year period. The relative incremental cost per 0.19 QATY ratio [changing the health state from a restored tooth (utility= 0.81) to a nonrestored tooth (utility = 1)] by sealing the molar ranged from $36.7 to $83.5 per 0.19 QATY. The incremental cost/QATY ratio was lower for sealing lower utilizers and for mandibular versus maxillary molars. Sealants improved overall utility of first permanent molars after 4 years. The 4-year cost/QATY ratio of sealing the first permanent molar varied by arch and type of utilizers. Sealing first permanent molars in lower dental utilizers is the most cost-effective approach for prioritizing limited resources.

Spinal Cord Stimulation versus Reoperation for Failed Back Surgery Syndrome: A Cost Effectiveness and Cost Utility Analysis Based on a Randomized, Controlled Trial

We analyzed the cost-effectiveness and cost-utility of treating failed back-surgery syndrome using spinal cord stimulation (SCS) versus reoperation. A disinterested third party collected charge data for the first 42 patients in a randomized controlled crossover trial. We computed the difference in cost with regard to success (cost-effectiveness) and mean quality-adjusted life years (cost-utility). We analyzed the patient-charge data with respect to intention to treat (costs and outcomes as a randomized group), treated as intended (costs as randomized; crossover failure assigned to a randomized group), and final treatment costs and outcomes. By mean 3.1-year follow-up, 13 of 21 patients (62%) crossed from reoperation versus 5 of 19 patients (26%) who crossed from SCS (P < 0.025) [corrected]. The mean cost per success was US $117,901 for crossovers to SCS. No crossovers to reoperation achieved success despite a mean per-patient expenditure of US $260,584. The mean per-patient costs were US $31,530 for SCS versus US $38,160 for reoperation (intention to treat), US $48,357 for SCS versus US $105,928 for reoperation (treated as intended), and US $34,371 for SCS versus US $36,341 for reoperation (final treatment). SCS was dominant (more effective and less expensive) in the incremental cost-effectiveness ratios and incremental cost-utility ratios. A bootstrapped simulation for incremental costs and quality-adjusted life years confirmed SCS's dominance, with approximately 72% of the cost results occurring below US policymakers' "maximum willingness to pay" threshold. SCS was less expensive and more effective than reoperation in selected failed back-surgery syndrome patients, and should be the initial therapy of choice. SCS is most cost-effective when patients forego repeat operation. Should SCS fail, reoperation is unlikely to succeed.

Cost-effectiveness of Spa treatment for fibromyalgia: general health improvement is not for free

To estimate the cost-effectiveness of an adjuvant treatment course of spa treatment compared with usual care only in patients with fibromyalgia syndrome (FM). 134 patients with FM, selected from a rheumatology outpatient department and from members of the Dutch FM patient association were randomly assigned to a 2(1/2) week spa treatment course in Tunisia or to usual care only. Results are expressed as quality-adjusted life years (QALYs) for a 6-month as well as a 12-month time horizon. Utilities were derived form the Short Form 6D (SF-6D) scores and the visual analogue scale (VAS) rating general health. Costs were reported from societal perspective. Mean incremental cost per patient and the incremental cost utility ratio (ICER) were calculated; 95% confidence intervals (CIs) were estimated using double-sided bootstrapping. The data of 128 (55 spa and 73 controls) of the 134 patients (96%) could be used for analysis. Improvement in general health was found in the spa group until 6 months of follow-up by both the SF-6D (AUC 0.32 vs 0.30, P < 0.05) and the VAS (AUC 0.23 vs 0.19, P < 0.01). After 1yr no significant between-group differences were found. Mean incremental cost of spa treatment was 1311 Euro per patient (95% CI 369-2439), equalling the cost of the intervention (thalassotherapy including airfare and lodging), or 885 Euro per patient based on a more realistic cost estimate. The temporary improvement in quality of life due to an adjuvant treatment course of spa therapy for patients with FM is associated with limited incremental costs per patient.

Falls and health status in elderly women following first eye cataract surgery: an economic evaluation conducted alongside a randomised controlled trial

Aim:To evaluate the cost-effectiveness of first eye cataract surgery compared with no surgery from a health service and personal social services perspective.Methods:An economic evaluation undertaken alongside a randomised controlled trial...

Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer

To assess the clinical effectiveness and cost-effectiveness of bevacizumab and cetuximab in the treatment of individuals with metastatic colorectal cancer (CRC). Searches of main electronic databases were conducted in April and May 2005. For the assessment of bevacizumab, trials were included if they recruited participants with untreated metastatic CRC for first-line treatment. Only trials comparing bevacizumab in combination with irinotecan and/or established fluorouracil (5-FU)-containing or releasing regimens given as first-line therapy were included. For the assessment of cetuximab, trials were included if they recruited participants with epidermal growth-factor receptor-expressing metastatic CRC who had previously failed irinotecan-including therapy. Independent cost-effectiveness models of bevacizumab and cetuximab were developed using survival modelling methods. Adding bevacizumab to irinotecan in combination with 5-FU/folic acid (FA) plus irinotecan resulted in a statistically significant increase in median overall survival (OS) of 4.7 months. Adding bevacizumab to 5-FU/FA resulted in a non-significant increase in median OS of 3.7 months within one study and 7.7 months in another. Adding bevacizumab to irinotecan, fluorouracil and leucovorin (IFL) resulted in a statistically significant increase in median progression-free survival (PFS) of 4.4 months. Adding bevacizumab to 5-FU/FA resulted in a statistically significant increase in median PFS of 3.7 months, and a statistically significant increase in time to disease progression of 3.8 months compared to FU/FA alone. An overall tumour response rate of 44.8% was reported for bevacizumab plus IFL compared to 34.8% for IFL plus placebo. This addition was statistically significant. The addition of bevacizumab to 5-FU/FA resulted in a significant difference in tumour response rate within one study, but not another. Bevacizumab in combination with IFL or 5-FU/FA was observed to result in an increase of grade 3/4 adverse events. The independent health economic assessment suggests that the cost-effectiveness of bevacizumab plus IFL is unlikely to be better than pound 46,853 per life-year gained (LYG); the cost-utility of bevacizumab plus IFL is unlikely to be better than pound 62,857 per quality-adjusted life-year (QALY) gained. The cost-effectiveness of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 84,607 per LYG; the cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. A Phase II trial reported a median OS duration of 8.6 months for patients receiving cetuximab plus irinotecan, plus a median time to progression of 4.1 months, a tumour response rate of 22.9% and suggested that treatment with cetuximab in combination with irinotecan is associated with significantly more adverse events (any grade 3 or grade 4 adverse event) than cetuximab monotherapy. The single arm study of cetuximab plus irinotecan reported a median OS duration of 8.4 months, a median time to progression of 2.9 months and a tumour response rate of 15.2%. The cost-effectiveness model suggested that the expected survival duration of patients receiving cetuximab plus irinotecan is 0.79 years (9.5 months) when the proposed continuation rule is applied. In order for cetuximab plus irinotecan to achieve a cost-utility ratio of pound 30,000 per QALY gained, treatment with cetuximab plus irinotecan must provide an additional 0.65 life years (7.8 months) over treatment with active/best supportive care, implying that survival in the active/best supportive care group must be 0.14 life years (1.7 months) or less. The trials indicate that bevacizumab in combination with 5-FU/FA, and bevacizumab in combination with IFL, is clinically effective in comparison to standard chemotherapy options for the first-line treatment of metastatic CRC. The health economic analysis suggests that the marginal cost-utility of bevacizumab plus IFL versus IFL is unlikely to be better than pound 62,857 per QALY gained, and the marginal cost-utility of bevacizumab plus 5-FU/FA versus 5-FU/FA is unlikely to be better than pound 88,658 per QALY gained. There is no direct evidence to demonstrate whether cetuximab in combination with irinotecan improves health-related quality of life or OS in comparison to active/best supportive care or oxaliplatin plus 5-FU/FA, although the evidence on tumour response rates suggests that cetuximab plus irinotecan has some clinical activity. While it is difficult to suggest whether cetuximab represents value for money, indirect comparisons suggest that the incremental cost-utility of cetuximab plus irinotecan is unlikely to be better than pound 30,000 per QALY gained. This review highlights a number of areas for further research, including clarifying the true impact of first-line bevacizumab in combination with irinotecan and/or infusional 5-FU/FA, without subsequent bevacizumab treatment following disease progression, on OS in patients with metastatic CRC who are representative of the typical population of CRC patients in England and Wales. Further research concerning the impact of therapies on health-related quality of life is essential.

The cost-utility of cinacalcet in addition to standard care compared to standard care alone for secondary hyperparathyroidism in end-stage renal disease: a UK perspective

Secondary hyperparathyroidism (SHPT) is a common side effect of end-stage renal disease (ESRD) and is associated with increased risk of fracture and cardiovascular events (CV). Current standard treatment includes dietary control, phosphate binders and vitamin D. However, many patients do not have their parathyroid hormone (PTH), calcium and phosphate levels controlled by this regimen. Cinacalcet is the first of a new class of calcimimetic drugs which suppress PTH production. Although there is convincing evidence of the impact of cinacalcet on serum biomarkers, the long-term clinical implications of treatment are less clear. The aim of this study is to estimate the cost-utility of cinacalcet as an addition to standard treatment of SHPT compared with standard treatment alone. A Markov model was developed to estimate the incremental cost-utility of cinacalcet. Uncertainty was explored through extensive sensitivity analysis. Compared with standard treatment, cinacalcet incurs average additional lifetime costs of pound21,167 per person and confers an additional 0.34 quality adjusted life years, resulting in an incremental cost-effectiveness ratio of pound61,890 (approximately euro89,000) per quality-adjusted life-year (QALY). Extensive one-way sensitivity analysis showed that cinacalcet was only likely to be considered cost-effective if the relative risk of mortality for people with very high levels of PTH was 2.2 compared with people whose PTH reached target levels, or if drug costs were considerably reduced. Probabilistic sensitivity analysis showed cinacalcet was very unlikely to be cost-effective at usual levels of willingness to pay in the National Health Service (NHS). Unless the cost of cinacalcet is considerably reduced, it is unlikely to be considered a cost-effective treatment for people with SHPT.

Cost-Effectiveness Analysis of Treatment Options for Acute Otitis Media

This study evaluated the costs and utility of observation and routine antibiotic treatment options for children with acute otitis media. The cost-effectiveness analysis was performed among children aged 6 months to 12 years seen in primary care offices. The interventions studied were watchful waiting as practiced in the Netherlands, delayed prescription, 5 days of amoxicillin, and 7 to 10 days of amoxicillin. The main outcome measure was cost per quality-adjusted life-year (QALY). In the base case analysis, delayed prescription was the least costly option and 7 to 10 days of amoxicillin was the most effective. The incremental cost utility ratio (ICUR) of 7 to 10 days of amoxicillin compared with delayed prescription was 56,000 dollars per QALY gained. Watchful waiting and 5 days of amoxicillin were inferior options. The results were sensitive to the rate of nonattendance in the delayed prescription strategy: when the rate was less than 23%, watchful waiting was the least costly option and delayed prescription was an inferior option. Probabilistic sensitivity analysis, in which all model variables were simultaneously varied, showed with 95% certainty that compared with delayed prescription, 7 to 10 days of amoxicillin had a 61% probability of having an ICUR of greater than 50,000 dollars per QALY gained, and watchful waiting had a 23% probability of having an ICUR of less than 50,000 dollars per QALY gained. Economically, an approach to the treatment of acute otitis media with either an initial period of observation or routine treatment with amoxicillin is reasonable.

Is There Value in Obtaining a Patient’s Willingness to Pay for a Particular Anesthetic Intervention?

Is There Value in Obtaining a Patient’s Willingness to Pay for a Particular Anesthetic Intervention?

Quality of life assessment in clinical practice in haemophilia treatment

The modern management of haemophilia has greatly influenced not only survival of patients, their clinical symptoms and orthopaedic outcome but also their perceived quality of life (QoL). QoL measures recently became an essential part of clinical trials being one of the most important patient-rated outcomes (PROs). Moreover, QoL assessment is essential in pharmacoeconomics. In clinical trials, not only clinical outcomes but also the so-called PROs and health-economic outcomes are included. Different types of economic evaluations may be conducted in order to describe the economic burden of a disease condition, to determine the cost of care and to assess and evaluate alternative treatments in terms of both costs and effects as well as benefits and outcomes with the aim of optimizing the use of resources. For these evaluations, the following analyses are performed: descriptive cost of illness study, incremental cost-effectiveness analysis, incremental cost-utility analysis and incremental cost-benefit analysis. By contrast, PROs are derived from direct patient reports and they allow to evaluate the impact of a disease and its treatment on patients' well-being and functioning. PROs include health-related quality of life, patient preferences/utilities, treatment satisfaction and other PROs such as functional assessment, etc. Choosing a QoL measure, study- and instrument-related aspects have to be taken into account. Finally, QoL assessment will become a part of the regular clinical assessment of persons with haemophilia, in order to provide trustworthy data of perceived well-being to be compared over time and in order to assess treatment efficacy and quality of care.

Optimising health care within given budgets: Primary prevention of cardiovascular disease in different regions of Sweden

This study investigated the consequences of applying strict health maximisation to the choice between three different interventions with a defined budget. We analysed three interventions of preventing cardiovascular diseases, through doctor's advice on smoking secession, through blood-pressure-lowering drugs, and through lipid-lowering drugs. A state transition model has been used to estimate the cost–utility ratios for entire population in three different county councils in Sweden, where the populations were stratified into mutually excluding risk groups. The incremental cost–utility ratios are being presented in a league table and combined with the local resources and the local epidemiological data as a proxy for need for treatment. All interventions with an incremental cost–utility ratio exceeding the threshold ratios are excluded from being funded. The threshold varied between 1687 Euro and 6192 Euro. The general reallocation of resources between the three interventions was a 60% reduction of blood-pressure-lowering drugs with redistribution of resources to advice on smoking secession and to lipid-lowering drugs. One advantage of this method is that the results are very concrete. Recommendations can thereby be more precise which hopefully will create a public debate between decision-makers, practising physicians and patient groups.

Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflunomide for rheumatoid arthritis in Germany

To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.

Cost utility in the United States of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone for the treatment of elderly patients with diffuse large B‐cell lymphoma

Findings from the Groupe d'Etude des Lymphomes Adultes LNH 98-5 study showed that rituximab added to combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) prolonged progression-free survival and overall survival in adults age >/= 60 years with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The current study was conducted to investigate the incremental cost utility of the addition of rituximab to CHOP (R-CHOP) compared with CHOP alone. Clinical prognosis of the time to disease progression and death was estimated using published evidence from the LNH 98-5 study (n = 399 patients) that was linked mathematically to published long-term outcome data on patients with DLBCL. Drug-acquisition costs were based on published data from formulary pricing sources, and the costs of cancer surveillance and end-of-life care were based on published literature sources. The authors assessed cost utility as the difference in costs between R-CHOP and CHOP divided by the increase in expected overall survival adjusted for quality of life. Over 5 years, it was projected that R-CHOP would prolong overall survival by 1.04 years. The mean cumulative cost of CHOP was 3358 dollars, and the mean cost of R-CHOP was 17,225 dollars, resulting in a cumulative net increase of 13,867 dollars. The posttreatment cancer surveillance cost for CHOP was 3950 dollars, compared with 5202 dollars for R-CHOP. It was estimated that R-CHOP would have a cost-utility ratio of 19,297 dollars per year of life gained compared with CHOP when adjusted for quality of life. R-CHOP remained cost effective over wide ranges of variables in sensitivity analyses. Compared with CHOP alone, it was predicted that R-CHOP would be cost effective in elderly patients with DLBCL.

The Economics of Topical Immunomodulators for the Treatment of Atopic Dermatitis

Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease frequently affecting infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5--20% of the paediatric population. First-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of antihistamines and oral antibacterials. Topical corticosteroids improve the lesions of atopic dermatitis; however, concern on the part of physicians and patients regarding adverse effects has led to reluctance to utilise topical corticosteroids early and especially for prolonged periods. Topical immunomodulators (TIMs), including tacrolimus ointment and pimecrolimus cream, were recently introduced for the treatment of atopic dermatitis. Clinical data show that TIMs are effective in atopic dermatitis, yet do not cause the significant adverse effects associated with topical corticosteroids. Questions remain regarding the place of TIMs as a treatment for atopic dermatitis and how to use them most effectively, from both therapeutic and pharmacoeconomic standpoints. Specifically, two major issues remain unresolved: (i) how TIMs measure up to other therapies, especially topical corticosteroids; and (ii) how members of the TIM drug class compare against each other. Previous research has established that atopic dermatitis has a significant impact on quality of life (QOL) and carries a substantial economic burden. Some studies have also measured the utility of various atopic dermatitis disease states. While there is a need for further research, early economic studies provide evidence that TIMs positively affect the QOL of patients and families. In certain patients, TIMs may be cost effective and have an acceptable incremental cost utility compared with topical corticosteroids.Making cost-effectiveness comparisons between tacrolimus and pimecrolimus is challenging because there are limited head-to-head comparative data. Given currently available efficacy data, the results of one study suggest that tacrolimus may be more cost effective than pimecrolimus in paediatric patients with moderate atopic dermatitis. The full economic and QOL benefits of both agents are yet to be completely understood. The studies reviewed herein are the first to delineate the pharmacoeconomic benefits of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs represent an exciting advance in the treatment of atopic dermatitis. Additional research will help determine the proper place of TIMs among the current array of therapeutic options for atopic dermatitis.

Pharmacoeconomics of Antiviral Therapy for Influenza in a Japanese Hospital Setting

We constructed a cost-effectiveness decision model to determine a hypothetical 'best treatment' pathway for patients presenting at our institution with influenza virus infection when the choice of treatment was either oseltamivir, zanamivir or a control therapy not active against influenza. The decision model was constructed using DATA 3.5 for evaluating the cost-effectiveness analysis of neuraminidase inhibitors from the perspective of the healthcare payer. The time horizon was set at 14 days based on the general duration of influenza infection in Japan. Clinical outcomes were mainly derived from reports and guidance published by the National Institute for Clinical Excellence in the UK. Japan-specific cost parameters incorporated into the decision model were taken from the Medical Fee Point Survey conducted at St Luke's International Hospital in accordance with medical fee receipts kept at our institution. The study included four professionals and a supporter who gathered information required for the analysis. In otherwise healthy adults, cost savings of yen831.6 (approximately $US6.72; 2002 values) in the oseltamivir group and an increment in cost of yen40.5 (approximately $US0.33) in the zanamivir group were achieved in comparison with the control group. In contrast, an incremental cost of yen288.4 (approximately $US2.33) was incurred in the oseltamivir group versus the control group when at-risk patients were assessed, but cost savings of yen159.8 (approximately $US1.29) were achieved in the zanamivir group. As a result of cost-effectiveness and cost-utility analyses in otherwise healthy adults, oseltamivir dominated the control therapy because cost savings in the oseltamivir group were made. In the zanamivir group the cost was incremental and the Incremental Cost-Utility Ratio (ICUR) compared with the control group was about yen13 000 (approximately $US107.34)/quality-adjusted life-year (QALY) gained. As a result of cost-effectiveness and cost-utility analyses in at-risk patients, in the oseltamivir group the cost was incremental and the ICUR compared with the control group was about yen230 000 (approximately $US2138.77)/QALY gained. As cost savings were made, zanamivir dominated the control therapy. While the cost effectiveness (from the perspective of a healthcare payer) of the neuraminidase inhibitors was superior to that of the control group in the treatment of otherwise healthy adults with influenza in our study, it seemed necessary to take other factors into consideration before recommending one agent over the other as a first-line therapy. On the other hand, we suggest that zanamivir is the drug of choice for use in at-risk patients, and we recommend, in the light of our results, that if zanamivir is not available another therapy should be given rather than oseltamivir. Since with influenza infections deaths and hospitalisations of at-risk patients impact on the Japanese community, decision-making on the appropriate therapy should take into account the particular patient group involved.