Implications to payers of switch from hospital-based intravenous immunoglobulin to home-based subcutaneous immunoglobulin therapy in patients with primary and secondary immunodeficiencies in Canada.

BACKGROUND: Switching primary/secondary immunodeficiency (PID/SID) patients from intravenous immunoglobulin (IVIg) to home-based subcutaneous immunoglobulin (SCIg) therapy reduces nurse time. A nurse shortage in Canada provides an important context to estimate the net economic benefit, the number of patients needed to switch to SCIg to recoup one full-time equivalent (FTE), and potential population-wide savings of reduced nurse time to a payer. METHODS: The net economic benefit was estimated by multiplying the hourly compensation for nurses in Canada by the hours required for each administration route. The number needed to switch to SCIg to gain one nurse FTE was estimated by dividing the work hours in a year by the average annual savings in nursing time in a PID population in Canada. The prevalence of treated PID/SID in Canada was calculated using provincial IgG audit data to extrapolate the potential population-wide savings of switching patients to SCIg therapy. FINDINGS: The net economic gain from switching one patient to home-based SCIg care would be C$2,603 (Canadian Dollars) in year 1 and C$2,948 each year thereafter. Switching 37 IVIg patients to SCIg would gain one nurse FTE. Switching 50% of the estimated 5,486 PID and SID patients in Canada receiving IVIg therapy to SCIg has the potential to save 223.3 nurse FTEs (C$23.2 million in labor costs). CONCLUSIONS: A shift from IVIg to less labor-intensive SCIg has the potential to help alleviate nurse shortages and reduce overall health care costs in Canada. Health care professionals might consider advocating for home-based SCIg therapy for PID/SID patients when clinically appropriate.

Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empirical antifungal therapy for neutropenic fever.

PURPOSE: An analysis was conducted that evaluated and compared the cost differences between caspofungin and liposomal amphotericin B when the medications were used as empirical antifungal therapy for persistent fever during neutropenia. METHODS: Rates of drug use and impaired renal function (IRF) were based on data from published studies. IRF was defined as a doubling of the serum creatinine level or, if the creatinine level was elevated at enrollment, an increase of at least 1 mg/dL. The estimates of the costs for drug acquisition and treating IRF were derived using published data and applied to compare caspofungin with liposomal amphotericin B. Sensitivity analyses were performed by varying the IRF and relative acquisition costs to assess the effect of these factors on the cost differences. RESULTS: The acquisition costs per patient were 6942 dollars for liposomal amphotericin B and 3996 dollars for caspofungin. The estimated cost per patient from IRF was 3173 dollars for liposomal amphotericin B and 793 dollars for caspofungin. Combining drug acquisition and IRF costs, the overall treatment cost per patient for caspofungin was 5326 dollars less than for liposomal amphotericin B. In sensitivity analyses of drug costs, the price of liposomal amphotericin B would have to be 23.95 dollars per vial for the overall treatment costs to be equal. CONCLUSION: Comparison of cost estimates derived from published data revealed that a combined estimate of acquisition costs and costs related to the treatment of IRF was lower for caspofungin than for liposomal amphotericin B for empirically treating patients with neutropenic fever.

Prospective study of amphotericin B formulations in immunocompromised patients in 4 European countries.

BACKGROUND: Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity. METHODS: The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe. RESULTS: Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection. CONCLUSION: This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.

The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy.

INTRODUCTION: The RENAAL (Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that, in hypertensive patients with type 2 diabetes mellitus and nephropathy, treatment with losartan plus conventional antihypertensive therapy (CT) reduced the relative risk of end-stage renal disease (ESRD) by 29% versus placebo over the time span of the study (mean patient follow-up of 3.4 years). The objective of this study was to project the effect of losartan compared with placebo on the lifetime incidence of ESRD and associated costs (from a US healthcare system perspective). METHODS: To estimate lifetime incidence of ESRD, we used a competing risks method to account for the risk of death without ESRD. We estimated the cost (US dollars, year 2002 values) associated with ESRD by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD, the cost of losartan study therapy and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Costs and outcomes were discounted by 3% per annum. RESULTS: We projected a lower lifetime incidence of ESRD for losartan patients (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in cost associated with ESRD of US dollars 31,803 per patient and a gain of 0.99 life-years per patient (0.70 discounted). After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a lifetime net saving of US dollars 24,632 per patient. CONCLUSION: Treatment with losartan plus CT in patients with type 2 diabetes and nephropathy reduced the within-trial incidence of ESRD and is projected to result in lifetime reductions in ESRD and associated costs, and increased survival, versus placebo.

Treatment outcomes in patients receiving conventional amphotericin B therapy: a prospective multicentre study in Taiwan.

OBJECTIVES: To evaluate treatment outcomes and healthcare resource use with conventional amphotericin B therapy for invasive fungal infections (IFIs). PATIENTS AND METHODS: A prospective observational study in hospitalized adult patients receiving amphotericin B treatment was undertaken at four hospitals in Taiwan. Patients were observed from the start of therapy to hospital discharge. RESULTS: A total of 108 patients (October 2000 to April 2002) were included in the study. Proven or probable IFIs as defined by the EORTC/MSG criteria were the reasons for the initiation of amphotericin B in 35.2% of the sample. A total of 24.1% patients developed nephrotoxicity (NT) (defined as a 50% increase in the baseline serum creatinine and achieving a peak of at least 2.0 mg/dL). Treatment of proven/probable IFIs [odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.61-10.75] was a significant predictor of the development of NT. The in-hospital mortality rate was 38.0%. Proven/probable IFIs (OR = 6.93, 95% CI = 2.62-18.29) and the development of NT (OR = 3.68, 95% CI = 1.22-11.04) were independent predictors of in-hospital mortality. For patients alive at discharge, those with NT had a trend of longer hospital stay compared with patients who had not developed NT (mean, 49.3 +/- 18.2 versus 29.3 +/- 22.3 days, P = 0.069). For patients who died, those who had developed NT died sooner (15.5 +/- 16.7 versus 33. 8 +/- 26.9 days, P = 0.0004). CONCLUSIONS: NT was associated with accelerated mortality and increased hospital stay for patients who survived. Using amphotericin B carefully or the use of antifungal agents with less potential for NT might improve patient outcomes.

Caspofungin versus amphotericin B for candidemia: a pharmacoeconomic analysis.

BACKGROUND: In a randomized, comparative, clinical trial, caspofungin was found to be as effective as amphotericin B deoxycholate (ampho B) for treating candidemia (favorable outcomes in 71.7% and 62.8% of patients, respectively) and exhibited a generally better safety profile, particularly with respect to impaired renal function (IRF) (P = 0.02). OBJECTIVE: The goal of this study was to examine whether cost savings generated from the reduced rates of IRF observed in the clinical trial would be enough to offset the higher acquisition cost of caspofungin relative to ampho B. METHODS: We developed an economic model in which 100 hypothetical patients with candidemia were treated with caspofungin or ampho B. Rates of IRF and duration of drug therapy were taken from the clinical trial. Information on the cost of treating IRF was obtained through a search of MEDLINE using the terms amphotericin and cost, amphotericin and resource, amphotericin and hospital, and amphotericin and toxicity; and the medical subject headings kidney failure, acute/drug therapy; kidney failure, acute/epidemiology; kidney failure, acute/etiology; kidney/drug effects; cost of illness; costs and cost analysis; kidney failure, acute, and economics; and kidney failure, acute/economics. In addition, the Web site was searched for relevant references, and the Merck publication alert system was used. Antifungal drug costs were estimated using data from IMS Health. Costs were reported in year-2003 US dollars. RESULTS: In the base case, the model projected that using caspofungin instead of ampho B would result in substantially lower treatment costs for IRF, which would more than offset the higher drug acquisition cost (cost-offset percentage, 122%), leading to a net mean savings of 758.60 US dollars per patient. These results were not very sensitive to the difference in daily drug cost, but were sensitive to the mean cost attributable to treating IRF. As that varied, the cost-offset percentage varied from 61% (substantial cost offset) to 183% (cost savings). CONCLUSIONS: The results of this economic model suggest that, based only on differences in drug acquisition cost and renal toxicity, the use of caspofungin instead of ampho B in patients with candidemia may be a cost-saving strategy from the perspective of a hospital.

Frequency of potential azole drug-drug interactions and consequences of potential fluconazole drug interactions.

PURPOSE: To assess the frequency of potential azole-drug interactions and consequences of interactions between fluconazole and other drugs in routine inpatient care. METHODS: We performed a retrospective cohort study of hospitalized patients treated for systemic fungal infections with an oral or intravenous azole medication between July 1997 and June 2001 in a tertiary care hospital. We recorded the concomitant use of medications known to interact with azole antifungals and measured the frequency of potential azole drug interactions, which we considered to be present when both drugs were given together. We then performed a chart review on a random sample of admissions in which patients were exposed to a potential moderate or major drug interaction with fluconazole. The list of azole-interacting medications and the severity of interaction were derived from the DRUGDEX System and Drug Interaction Facts. RESULTS: Among the 4,185 admissions in which azole agents (fluconazole, itraconazole or ketoconazole) were given, 2,941 (70.3%) admissions experienced potential azole-drug interactions, which included 2,716 (92.3%) admissions experiencing potential fluconazole interactions. The most frequent interactions with potential moderate to major severity were co-administration of fluconazole with prednisone (25.3%), midazolam (17.5%), warfarin (14.7%), methylprednisolone (14.1%), cyclosporine (10.7%) and nifedipine (10.1%). Charts were reviewed for 199 admissions in which patients were exposed to potential fluconazole drug interactions. While four adverse drug events (ADEs) caused by fluconazole were found, none was felt to be caused by a drug-drug interaction (DDI), although in one instance fluconazole may have contributed. CONCLUSIONS: Potential fluconazole drug interactions were very frequent among hospitalized patients on systemic azole antifungal therapy, but they had few apparent clinical consequences.

Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge?

BACKGROUND: An increasing number of health-care systems, both public and private, such as managed-care organizations, are adopting results from cost-effectiveness (CE) analysis as one of the measures to inform decisions on allocation of health-care resources. It is expected that thresholds for CE ratios may be established for the acceptance of reimbursement or formulary listing. OBJECTIVE: This paper provides an overview of the development of and debate on CE thresholds, reviews threshold figures (i.e., cost per unit of health gain) currently proposed for or applied to resource-allocation decisions, and explores how thresholds may emerge. DISCUSSION: At the time of this review, there is no evidence from the literature that any health-care system has yet implemented explicit CE ratio thresholds. The fact that some government agencies have utilized results from CE analysis in pricing/reimbursement decisions allows for retrospective analysis of the consistency of these decisions. As CE analysis becomes more widely utilized in assisting health-care decision-making, this may cause decision-makers to become increasingly consistent. CONCLUSIONS: When CE analysis is conducted, well-established methodology should be used and transparency should be ensured. CE thresholds are expected to emerge in many countries, driven by the need for transparent and consistent decision-making. Future thresholds will likely be higher in most high-income countries than currently cited rules of thumb.

Losartan reduces the costs associated with nephropathy and end-stage renal disease from type 2 diabetes: Economic evaluation of the RENAAL study from a Canadian perspective.

BACKGROUND: The Reduction of Endpoints in NIDDM [non-insulin-dependent diabetes mellitus] with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated the renoprotective effects of losartan in patients with nephropathy from type 2 diabetes. OBJECTIVE: To perform an economic evaluation of the costs associated with end-stage renal disease (ESRD) from a Canadian public health perspective, based on the clinical outcomes reported in the RENAAL study. METHODS: ESRD-related costs were determined by estimating the mean number of days with ESRD multiplied by the daily cost of ESRD (140 dollars); mean days with ESRD were calculated by subtracting the area under the Kaplan-Meier survival curve for time to the first event of ESRD or all-cause mortality from the area under the curve for all-cause mortality. Daily ESRD cost was determined using Canadian specific data sources. ESRD-related cost savings with losartan were obtained by subtracting the ESRD-related costs of the losartan group from those of the placebo group. Net cost savings were ESRD-related cost savings with losartan minus the drug cost of losartan. RESULTS: Losartan reduced the number of ESRD days by 33.6 per patient over 3.5 years (95% CI 10.9 to 56.3) compared with placebo. Losartan reduced ESRD-related costs by 4,695 dollars per randomized patient over 3.5 years (95% CI 1,523 dollars to 7,868 dollars). After accounting for the drug cost of losartan, net cost savings with losartan were 3,675 dollars per randomized patient over 3.5 years. CONCLUSION: Losartan therapy for patients with nephropathy from type 2 diabetes reduces the clinical incidence of ESRD and can result in considerable cost savings for the Canadian public health system.

Burden of hospitalization of patients with Candida and Aspergillus infections in Australia.

OBJECTIVES: This study examined the burden of hospitalization of patients with Aspergillus and Candida infections in Australia from 1995 to 1999. METHODS: Data were extracted from the National Hospital Morbidity Database. A hospitalization with an aspergillosis diagnosis was defined as any discharge with a diagnosis of aspergillosis. A hospitalization with a candidiasis diagnosis was defined as any discharge with a diagnosis of disseminated, invasive, or non-invasive candidiasis. Outcome measures included number of hospitalizations, length of stay (LOS), cost (AUS$), and mortality. RESULTS: 4583 hospitalizations with an aspergillosis diagnosis and 57,758 hospitalizations with a candidiasis diagnosis were identified. These hospitalizations were associated with a total of 813,398 hospital days, AUS$563 million in cost, and 4967 in-hospital deaths during the study period. The mean LOS for a hospitalization with an aspergillosis diagnosis was 12 days, cost AUS$9,334, and was associated with 8% mortality. For disseminated, invasive, and non-invasive candidiasis, the respective mean LOS were 31, 17, and 12 days; costs were AUS$33,274, AUS$12,954, and AUS$7,694; and mortality was 26%, 9%, and 8%. CONCLUSIONS: Hospitalizations with diagnoses for fungal infections were associated with lengthy hospital stays, high costs, and high mortality.

Productivity cost benefit to employers of treating migraine with rizatriptan: a specific worksite analysis and model.

Employers in the United States might not be aware of the productivity costs of migraine or the extent to which those costs can be reduced by optimal treatment. An economic model was developed to enable employers to estimate the productivity costs of migraine to their company and the savings that will accrue if those patients who suffer from migraine are treated with rizatriptan. Analyses were run for both a major financial services corporation and a representative U.S. company. The major financial services corporation, with 87,821 employees, is projected to lose 538 person-years annually, at an estimated cost of 23.8 million dollars. A representative U.S. company with 10,000 employees is projected to lose 46.0 person-years of productive effort annually as a result of migraine, valued at approximately 1.94 million dollars. The value of the annual work loss avoided if migraine is treated with rizatriptan is projected at 10.3 million dollars for the financial services corporation and 841,000 dollars for the representative U.S. company. There is a substantial productivity cost burden of migraine from a U.S. employer perspective. These productivity costs can be reduced significantly by treating migraine headaches with rizatriptan.

Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation.

OBJECTIVE: To evaluate the within-trial effect of losartan and conventional antihypertensive therapy (CT) compared with placebo and CT on the economic cost associated with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study was a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the renal protective effects of losartan on a background of CT (excluding ACE inhibitors and angiotensin II receptor agonists [AIIAs]) in patients with type 2 diabetes and nephropathy. The primary composite end point was doubling of serum creatinine, ESRD, or death. Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time. The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System. Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy. RESULTS-We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years (P = 0.004, 95% CI 10.9-56.3). This reduction in ESRD days resulted in a decrease in cost associated with ESRD of 5144 US dollars per patient (P = 0.003, 95% CI 1701 to 8587 US dollars). After accounting for the cost of losartan, the reduction in ESRD days resulted in a net savings of 3522 US dollars per patient over 3.5 years (P = 0.041, 143 to 6900 US dollars). CONCLUSIONS: Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD, but also resulted in substantial cost savings.

Compliance and persistence with newer antihypertensive agents.

Individuals with hypertension need to stay on therapy with antihypertensive medication to obtain the full benefits of blood pressure reduction. There are important differences in tolerability across antihypertensive drug classes, and these differences influence the extent to which patients are willing to continue taking their drugs. Three separate sources of evidence--postmarket surveillance studies, medical/prescription database studies, and discontinuation of study medication in long-term endpoint clinical trials--support the proposition that angiotensin II antagonists, the newest class of antihypertensives, are well tolerated, and that patients whose initial treatment is an angiotensin II antagonist are more likely to persist with therapy than patients who use other classes of antihypertensives. Recent landmark trials with losartan in hypertensive patients with left ventricular hypertrophy (Losartan Intervention For Endpoint reduction [LIFE]) and in diabetes (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL]) demonstrated excellent tolerability, a high level of persistence, and clinical benefits exceeding those provided by blood pressure control alone for the prototype angiotensin II antagonist in clinical settings.

Impact of migraine symptoms on health care use and work loss in Canada in patients randomly assigned in a phase III clinical trial.

BACKGROUND: Migraine is prevalent and associated with substantial direct and indirect costs that may vary across geographic and national boundaries. The effects of migraine, self-reported by Canadians, on health care resource use as well as paid and unpaid work loss were examined. PATIENTS AND METHODS: The Migraine Background Questionnaire (MBQ) was self-administered during the screening visit of a phase III clinical trial of rizatriptan (a potent, selective 5-hydroxytryptamine(1B/1D)-receptor agonist or 'triptan'). Patients suffering from moderate to severe migraine in the previous six months were offered the opportunity to participate. Migraine frequency was determined and costs were estimated and assigned based on known direct costs of health care resource utilization, and indirect costs of paid and unpaid work and productivity loss. RESULTS: One hundred thirty-four patients completed the MBQ. In the previous year, 89% of those patients reported visiting a clinic, 23% reported visiting an emergency room and 5% reported being hospitalized for migraine. Patients reported an average of 6.5 days absent from work, 44 days working with migraine headache and 10.4 reduced workday equivalents due to ineffectiveness at work with migraine. Based on data obtained from the Ontario, the average overall annual cost due to migraine was estimated to be 3,025 dollars/patient; most of this (87%) due to indirect costs. CONCLUSION: In Canada, patients with moderate to severe migraine, as identified in a phase III clinical trial, reported lost work days and reduced effectiveness while at work, as well as increased health care resource utilization due to migraine. The associated cost was estimated to be substantial.

Losartan reduces the burden and cost of ESRD: public health implications from the RENAAL study for the European Union.

Type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in most industrialized countries in Europe. The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) Study evaluated the renal protective effects of losartan versus placebo on a background of non-ACE-I/non-AIIA conventional antihypertensive therapy in 1513 patients with type 2 diabetes and nephropathy. Losartan reduced the incidence of doubling of serum creatinine, end-stage renal disease (ESRD), or death by 16% (P=0.022) and reduced the risk of progression to ESRD, defined as the initiation of dialysis or transplantation, by 29% (P=0.002). We set out to estimate the potential effect of losartan on the burden and costs associated with ESRD over 3.5 years in the European Union (EU). The risk reduction in new cases of ESRD was calculated by combining type 2 diabetes population estimates for the EU with the percent absolute risk reduction of ESRD in patients treated with losartan as observed in RENAAL. The number of days each patient experienced ESRD was defined as the length of time from onset of ESRD until the minimum of death or 3.5 years. ESRD-free person-years avoided with losartan treatment were calculated by combining the population estimate with the ESRD days avoided divided by number of days in a year. ESRD costs from Germany were used to approximate the potential cost savings from reduced time with ESRD and fewer ESRD cases on a EU wide basis. There are approximately 700,000 diagnosed type 2 diabetes patients with proteinuria (urine albumin/creatinine >or=300 mg/g) in the EU. The addition of losartan to the treatment regimen of these patients is expected to lead to a reduction of 44,100 cases of ESRD, 64,400 fewer person-years with ESRD, and reduce ESRD-related costs by euro 2.6 billion over 3.5 years based on RENAAL data. Treatment with losartan not only reduced the incidence of ESRD, but also can result in substantial cost savings in the European Union.

Antihypertensive persistence and drug class.

BACKGROUND: Noncompliance with antihypertensive therapy is a major problem that hinders successful hypertension management. OBJECTIVE: To study antihypertensive drug persistence for hypertensive patients in routine clinical settings. METHODS: Hypertensive patients were retrospectively studied (1994 through 1998) using databases managed by Saskatchewan Health. The study population (46,458 people) included all patients with an International Classification of Diseases-9 code of 401, 402, 403 or 404, or any four-digit code included in these categories, who received at least one antihypertensive therapy prescription during the first 4.5 years of the study and received no antihypertensive therapy 12 months before the dispensing of the first therapy. Prescriptions were placed into the following drug classes: angiotensin II antagonists, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers and diuretics. Persistence was determined for four intervals in the patient's therapy at 180, 360, 540 and 720 days. RESULTS: Drug class had a statistically significant (P<0.001) effect on persistence. Angiotensin II antagonists had the highest persistence followed by angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers and diuretics. Persistence decreased as the time interval increased. Females were significantly more persistent than males (P<0.005), and elderly patients were significantly more persistent than younger patients (P<0.001) at each of the four time intervals. For angiotensin II antagonists, age and sex did not affect persistence. CONCLUSIONS: The consistently higher persistence associated with the use of angiotensin II antagonists may improve the management of hypertension.