A cost-effectiveness evaluation of amlodipine usage in patients with coronary artery disease in Sweden.

The objective of this analysis was to calculate the cost-effectiveness of amlodipine therapy in patients with coronary artery disease in Sweden. It is hypothesised that treatment with amlodipine will have an impact on overall cardiovascular disease treatment costs, resulting in a positive cost-effectiveness profile. A Markov cohort simulation model was constructed to simulate event-related and procedure-related health economic outcomes of coronary artery disease populations on amlodipine versus those on placebo. Patient level data from the Prospective Evaluation of the Vascular Effects of Norvasc Trial was used to populate the model. The total number of adverse cardiovascular clinical outcomes experienced over a three-year period was lower for patient on amlodipine than for those on placebo. The rate of hospitalisation per patient due to angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, congestive heart failure, and myocardial infarction in the placebo cohort was 64.7%, while the rate in the amlodipine cohort was 46.9%. The cost per patient was Swedish kroner (SEK)26,600 for amlodipine patients and SEK27,400 for placebo patients. The use of amlodipine resulted in improved clinical outcomes as well as a slight savings in cost over a three-year period.

A multinational pharmacoeconomic evaluation of acute major depressive disorder (MDD): a comparison of cost-effectiveness between venlafaxine, SSRIs and TCAs.

METHODS: We conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study. RESULTS: Initiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US). CONCLUSIONS: Within the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets. ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization.

The health economic impact of antidepressant usage from a payer's perspective: a multinational study.

A multinational decision analytic model was developed to examine the treatment of major depressive disorder (MDD) in 10 European and American countries. Input to the model was obtained from a meta-analysis of current clinical trial data obtained from the published literature, and local clinical and health economic experts in each market. The patient- and policy-level impact of MDD treatment was measured in each of the 10 markets. The total expected cost per patient for treating MDD with venlafaxine XR during the six-month acute phase of MDD was the lowest expected cost in nine of the 10 countries studied, resulting in savings to the primary payer in almost all markets. As well as the cost savings, the higher efficacy and lower rate of dropout found for venlafaxine XR translate to a greater number of symptom-free-days (SFDs) per patient. The results of this investigation show that use of venlafaxine XR in most settings across Europe and the Americas will have a favourable impact on healthcare payer budgets and the overall mental health of MDD patients.

The cost-effectiveness of doxazosin for the treatment of hypertension in type II diabetic patients in the UK and Italy.

The objective of this analysis was to assess the cost-effectiveness of achieving 'tight control' versus 'less tight control' of blood pressure, as defined in the UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and Italy. The effect of including doxazosin in a 'tight control' combination therapy was analysed. Given doxazosin's positive impact on lipid levels in addition to its antihypertensive effect, it is hypothesised that treatment including doxazosin will reduce the incidence of macrovascular complications. For each country, a Markov model was constructed to simulate macrovascular outcomes of patients on various drug combinations. Transitional probabilities were based on the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of the cohort and the lipid-lowering properties of doxazosin using Framingham risk equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867 Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent when included in a combination therapy in the treatment of hypertension in the diabetic populations of the UK and Italy.

A retrospective analysis comparing the costs and cost effectiveness of amlodipine and enalapril in the treatment of hypertension.

A comparison of treatment costs and cost effectiveness was performed retrospectively by using patient-level data from a randomized, controlled, one-year clinical trial of amlodipine and enalapril in the treatment of mild-to-moderate hypertension. Unit costs of amlodipine and enalapril were applied to the daily dosages of individual patients to calculate the total costs and average costs per patient in each treatment group in the clinical trial on an intent-to-treat basis. Efficacy rates were used to calculate the average treatment costs per success in blood pressure control. Although not statistically significant, amlodipine treatment resulted in a higher efficacy (89.5%) vs. enalapril (85.2%). The average costs per amlodipine-treated patient were consistently lower (-$112.30) than for the enalapril-treated patient by week 50. Treatment with amlodipine resulted in an average cost per success of $609 per patient compared with $772 per enalapril-treated patient. A sensitivity analysis revealed that, in the treatment of mild-to-moderate hypertension over the 50-week treatment period, amlodipine would remain less costly than enalapril, with a decrease in the cost of enalapril of up to 17%, and would remain more cost effective, with a 21% decrease in the cost of enalapril.

Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom.

OBJECTIVE: To estimate the cost effectiveness of different classes of antidepressants in the UK National Health Service. DESIGN, PATIENTS AND INTERVENTIONS: The use of the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with that of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with major depressive disorder (MDD). A meta-analysis determined the clinical success rate, and a decision tree was constructed by interviewing general practitioners and psychiatrists. Adding pharmacological and nonpharmacological treatment costs, meta-analytic rates were applied to the decision tree to calculate the expected cost and outcome for each drug. Cost effectiveness was determined using a composite measure of outcome [symptom-free days (SFD)]. MAIN OUTCOME MEASURES AND RESULTS: The meta-analysis included data from 44 studies on 4033 patients. The highest overall efficacy rate for outpatients with MDD was with venlafaxine use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with venlafaxine yielded the lowest outpatient cost for a SFD (10.53 Pounds), compared with 13.23 Pounds for SSRIs and 15.52 Pounds for TCAs (1998 values). CONCLUSIONS: Using this economic model, venlafaxine appears to be a cost-effective treatment for outpatients with MDD in the UK.

A pharmacoeconomic evaluation of two new products for the treatment of overactive bladder.

The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.

The management of depression: the implications for managed care--roundtable discussion: Part 2.

One of the most commonly utilized drug classes today is antidepressant therapy, which accounts for billions of dollars in spending. Pharmacoeconomic tools may play an influential role in formulary decision making, particularly in this drug class. In part 2 of the roundtable discussion, a pharmacoeconomic model is presented that may clarify the health economic effects of placing serotonin-norepinephrine reuptake inhibitors on the drug formulary, particularly in the context of other antidepressant medications.

Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials.

The purpose of this study was to summarize and compare the clinical success rates of extended-release venlafaxine, some selective serotonin reuptake inhibitors (SSRIs), and certain tricyclic antidepressants (TCAs). A meta-analytic approach was used to synthesize outcomes from published randomized controlled trials involving patients scoring > or =15 on the Hamilton Rating Scale for Depression (HAM-D) or > or =18 on the Montgomery-Asberg Depression Rating Scale (MADRS). Searches of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases were performed, as were searches of references from retrieved articles and reviews. Drugs included in the comparison were extended-release venlafaxine (venlafaxine-XR); the SSRIs citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the TCAs amitriptyline, imipramine, desipramine, and nortriptyline. Therapeutic success was defined as a 50% decrease in the HAM-D or MADRS score. Data were extracted by 2 independent evaluators, with differences resolved through consensus discussions. Weighted mean success rates were calculated for each drug class, using a random-effects model. The resulting data represent 44 trials with 63 study arms and 4033 patients with depression. Venlafaxine-XR demonstrated a 73.7% success rate, which was statistically significantly greater than that of the studied SSRIs (61.1%) and TCAs (57.9%) (P<0.001). Thus this meta-analysis of randomized controlled studies of patients with depression suggests that venlafaxine-XR is clinically superior in efficacy to SSRIs and TCAs. Venlafaxine-XR also had universally lower, though nonsignificant, dropout rates.

A pharmacoeconomic evaluation of major depressive disorder (Italy).

OBJECTIVE: To determine the most cost-effective oral therapy for the treatment of Major Depressive Disorder (MDD) in Italy. METHOD: We conducted a pharmacoeconomic evaluation based on a decision analytic model that examined the treatment of major depressive disorder (MDD) in Italy. The analysis compared the serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine extended-release (venlafaxine XR), to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). A meta-analysis was performed to determine the clinical rates of success. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each anti-depressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed 'symptom-free days'. A policy analysis was conducted to estimate the financial impact to the Servizio Sanitario Nazionale (SSN). RESULTS: Treatment of MDD with venlafaxine XR yielded the highest overall efficacy rates for outpatients (73.7%) versus SSRIs (61.4%) and TCAs (59.3%), and inpatients (62.3%) versus SSRIs (58.6%) and TCAs (58.2%). Venlafaxine XR had the lowest dropout rates due to lack of efficacy (4.8%) versus SSRIs (8.4%) and TCAs (6.8%), and adverse drug reactions (10.9%) versus SSRIs (17.4%) and TCAs (23.1%). Initiating treatment of MDD with venlafaxine XR yielded the lowest expected cost for outpatients and for inpatients. The total resulting savings for the SSN at a 5% venlafaxine XR utilization was estimated between L 963 million and L 3,210 million. CONCLUSION: This study confirms that venlafaxine XR is generally a cost-effective treatment of MDD. Additionally, the results of this investigation suggest that increased utilization of venlafaxine XR will favorably impact the SSN.

Pharmacoeconomic analysis of topical treatments for tinea infections.

BACKGROUND: A payor-perspective economic analysis of the topical creams ciclopirox, clotrimazole, ketoconazole, miconazole, and terbinafine (TER) used to treat dermatophytosis has been made. This pharmacoeconomic evaluation was conducted in Austria, Germany, and Switzerland. METHODS: A four-phase approach was used. Phase 1: experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process. Phase 2: meta-analysis was used to determine success, failure, and relapse rates. Phase 3: economic analyses performed included cost of regimen, total expected cost, and cost-effectiveness. Phase 4: sensitivity analyses (robustness analysis) were also executed to determine the validity of the assumptions. RESULTS: In the total expected cost analysis, TER demonstrated the lowest overall cost of treating patients. Terbinafine also provided the highest number of disease-free days during the analytic time horizon and, consequently, the lowest cost per disease-free day. Sensitivity analyses suggest that TER is the most cost-effective topical product for treating dermatophytosis in Austria, Germany, and Switzerland. CONCLUSIONS: All analytic scenarios suggest that TER therapy demonstrates lower expected costs and generates more DFDs when compared with the fungistatic topical therapies included in this pharmacoeconomic analysis. Terbinafine is expected to be the most cost-effective choice in Austria, Germany, and Switzerland for treatment of dermatophytosis minor.

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The treatment of colorectal cancer continues to pose major challenges for oncologists throughout the world. Uracil and tegafur (UFT), as an oral agent, represents a new patient-focused approach to managing a malignancy with few treatment alternatives other than an intravenous fluorouracil (5-FU)-based regimen. The ability of UFT to achieve equivalent clinical outcomes compared with continuous 5-FU infusion, along with its oral formulation and mild toxicity profile, provide a compelling backdrop for fiscal analysis. An economic assessment of therapy attributes and effects would, therefore, be prudent and necessary when deliberating the adoption of this chemotherapy regimen. We developed a pharmacoeconomic model in Brazil and Argentina identifying clinical practices associated with chemotherapy administration and adverse event management practices from a panel of physicians assembled in each country. Practice patterns and clinical events were then evaluated for resource utilisation trends. The perspective of this pharmacoeconomic analysis was that of the healthcare payor. Country-specific charge data were applied to the identified resources to arrive at an average cost per patient receiving a 6-cycle course of 5-FU with either levamisole and/or leucovorin as a modulator vs a modelled oral UFT/leucovorin regimen. As a comparator, the oral UFT/leucovorin regimen was modelled based on the expert panel's input. Adverse events and incidence data were derived from clinical trial data for both agents. Both agents were analysed in the treatment of metastatic disease and as adjuvant therapy. The principal findings of a cost-minimisation analysis in Brazil revealed approximately equivalent treatment costs for both regimens in the adjuvant setting. When analysing the metastatic treatment arm, costs diverged by $R335/per patient ($R = Reals - the currency of Brazil) in favour of a UFT regimen. The profile in Argentina yielded more dramatic differences, with a UFT regimen costing $P782/per patient ($P = Pesos - the currency of Argentina) less than a 5-FU regimen in the adjuvant setting. In the treatment of metastatic disease, a UFT regimen provided $P1188/per patient in savings over a 5-FU regimen. These differences are predominantly driven by the mild toxicity profile of UFT and its corresponding less severe adverse event management practice patterns. In addition, the oral formulation of UFT versus intravenous 5-FU provides for ease of administration, lowering the total cost of care as well as likely impacting on the patient's quality of life. The pharmacoeconomic results suggest that a UFT regimen is a useful and economical alternative to the standard 5-FU regimen in the treatment of colorectal cancer in Brazil and Argentina.

Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.

PURPOSE: A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS: Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS: Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION: The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.

A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America.

The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.

Building a computerized disease management operating system.

Under the increasing pressures of the marketplace, there has been a determined move in health care toward the development of disease management systems that improve efficiency, control costs, and ensure the best possible clinical outcome. Achieving these goals requires the ability to perform global analysis of complex and dynamic systems, beginning with point-of-care data collection and including the potential for multiple interfaces along the continuum of care. Our center has developed an integrated disease management system that enables the clinician to continuously monitor and assess relevant clinical and financial information flowing through the practice, providing robust and rigorous outcomes, health economic analysis, and pharmacoeconomic analysis of care at every step in the delivery process. This paper describes the results of pilot studies of the analytic capability of the system and includes an overview of the conceptual parameters employed in its development.

Full-cost determination of different levels of care in the intensive care unit. An activity-based costing approach.

We applied an activity-based costing methodology to determine the full cost of intensive care service at a community hospital, a university hospital and a health maintenance organisation (HMO)-affiliated hospital. A total of 5 patient care units were analysed: the intensive care unit (ICU) and surgical ICU (SICU) at the university setting, the ICU at the community setting, and the SICU and cardiac care unit at the HMO setting. The selection of the different ICU types was based on the types of critical care units that were found in each setting (e.g. the HMO did not have an ICU). Institution-specific cost data and clinical management parameters were collected through surveys and site visits from the 3 respective organisation types. The analysis revealed a marked increase in patient-minute cost associated with mechanical ventilation. Higher costs associated with prolonged neuromuscular blockade have important economic implications with respect to selection of an appropriate neuromuscular blocking agent.

Clinical and economic factors in the treatment of onychomycosis.

Onychomycosis is a fungal infection of fingernails and toenails, most cases of which are caused by dermatophytes. The disease accounts for 15% of all nail disease, and affects approximately 2 to 3% of people of all ages and both sexes. Topical treatment with tioconazole, amorolfine or ciclopirox has limited effectiveness. Oral griseofulvin 500 to 1000mg daily has been the mainstay of treatment, but prolonged therapy is required and success rates are low. Therapy with itraconazole 200mg daily for 3 to 6 months is more effective (70 to 85% success), although so-called 'pulse' therapy has shown similar success with potentially fewer adverse effects. Terbinafine 250mg daily produces clinical and mycological cure in approximately 80% of patients treated for 6 and 12 weeks for fingernail and toenail infections, respectively. The overall costs of treating onychomycosis are substantial, and it has been estimated that direct costs for Medicare patients with the disease were $US43 million in 1 year. In addition, the disease has a negative impact on quality of life, in the domains of mental functioning, health concern, social functioning, and physical appearance. Few pharmacoeconomic analyses have been published, but all have indicated an advantage of oral terbinafine over griseofulvin and other oral agents. To date, no economic studies have been performed on topical agents, pulse therapy or combination treatments.

Economic and quality of life outcomes: the four-step pharmacoeconomic research model.

Increasingly, economic data are being considered in formulary decisions. In oncology, pharmacoeconomic evaluations are essential to help decision makers weigh the associated costs and outcomes of competing chemotherapeutic interventions. In this article, we present a four-step pharmacoeconomic research model that can be customized for specific provider or payer systems. The model encompasses problem identification, clinical management analysis, three pharmacoeconomic analyses (cost consequence, expected cost, and cost effectiveness), and a sensitivity analysis--the rank order stability analysis (ROSA)--to validate the findings.