Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of iron overload in lower-risk, transfusion-dependent myelodysplastic syndrome patients.

OBJECTIVE: The study evaluated the cost effectiveness of deferasirox (Exjade * ) compared to non-proprietary desferrioxamine (DFO) for the control of transfusional iron overload in lower risk myelodysplastic syndromes (MDS) patients. A UK National Health Service perspective was adopted. METHODS: Recent clinical evidence has demonstrated the efficacy and safety of deferasirox in transfusion-dependent MDS patients with elevated serum ferritin levels. An economic model was used to extrapolate the clinical benefits of iron chelation therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition, drug administration and monitoring, and quality of life (utility) outcomes associated with mode of drug administration were derived from a variety of sources. The incremental cost per QALY gained for deferasirox was estimated. Costs and outcomes were discounted at 3.5% in line with UK standards. RESULTS: The base-case cost effectiveness of deferasirox versus DFO was estimated to be £20,822 per QALY gained, the key driver being the additional quality of life benefits associated with a simpler mode of administration for deferasirox. A mean survival benefit for both forms of ICT of 4.5 years was estimated. The results were sensitive to drug dose, days of DFO administration, and patient weight. CONCLUSIONS: In the UK, a cost per QALY below £20,000-30,000 is considered cost effective. Hence, the results from this economic analysis suggest deferasirox is cost effective in lower risk, transfusion-dependent, MDS patients. Limitations with the analysis include a lack of comparative randomised controlled trial evidence, in particular to differentiate survival and clinical outcomes for deferasirox and DFO.

Assessment of health economics in Alzheimer's disease (AHEAD) based on need for full-time care.

OBJECTIVE: To develop a framework for estimating the long-term health and economic consequences of AD based on patient characteristics at a given point in time. METHODS: A pharmacoeconomic model (Assessment of Health Economics in Alzheimer's Disease, AHEAD) was developed based on equations that relate the probability of needing full-time care (FTC) over time to patient characteristics summarized in index scores. These equations were developed from published data on interquartile times until FTC is needed and until death, using nonlinear regressions of the resulting index-specific hazards. These equations were then incorporated into a hidden Markov framework that allows for calculation of expected time to FTC and to death, as well as of the economic consequences of disease progression. There are three major states in the model: not requiring FTC ("pre-FTC"), requiring FTC, and death. RESULTS: Outcomes for five sample patients are derived to illustrate application of the AHEAD model. The impact of altering disease markers in these patients is also considered. CONCLUSION: The need for a generally applicable tool to forecast long-term outcomes based on relatively short-term data is becoming increasingly acute with the advent of new therapies for AD. The AHEAD model provides a relatively simple framework for the prediction of time to FTC requirement based on short-term observed data such as those from clinical trials. Although subject to the uncertainties inherent in modeling, the model nevertheless provides a standard estimation technique that may facilitate comparisons between existing and emerging therapies.

Economic analysis of initial HIV treatment. Efavirenz- versus indinavir-containing triple therapy.

OBJECTIVE: To compare the clinical and economic outcomes associated with triple therapy containing efavirenz or indinavir and 2 nucleoside reverse transcriptase inhibitors (NRTIs; zidovudine and lamivudine) in HIV-positive patients. DESIGN AND SETTING: An economic model based on viral load and CD4+ cell counts to predict long term outcomes such as progression to AIDS and AIDS-related death was developed and then analysed using data from a randomised clinical trial. Cost estimates from the healthcare system perspective were based on data from 6 state, all-payor databases, the AIDS Cost and Services Utilisation Study, and other literature. Analyses were carried out for time horizons between 5 and 15 years. PATIENTS AND INTERVENTIONS: HIV-positive patients with limited exposure to NRTIs. Initial regimens consisted of efavirenz or indinavir, each combined with 2 NRTIs. A maximum of 2 switches to other regimens was permitted. MAIN OUTCOME MEASURES AND RESULTS: The efavirenz-containing triple therapy regimen was predicted to prolong survival at a savings of up to 10,923 US dollars (1998 values) relative to initial therapy with the indinavir-containing regimen. Patients who receive efavirenz are expected to have 11% greater survival at 5 years and fewer treatment failures (28 vs 52%, at 2 years). Overall, the economic and health benefits predicted for the efavirenz-containing regimen were robust to reasonable variation in key parameters. CONCLUSIONS: The superior clinical trial outcomes for efavirenz-containing regimens should translate into substantial economic and health benefits.

Anticoagulant prophylaxis against stroke in atrial fibrillation: effectiveness in actual practice.

BACKGROUND: Randomized trials have shown a beneficial effect of anticoagulation with warfarin to prevent stroke in atrial fibrillation. It is not known whether the same effect will be obtained in actual practice. The authors conducted a prospective observational study to evaluate the effect of preventive anticoagulation in patients with atrial fibrillation in 2 practice settings in Montreal. METHODS: Of the 1725 outpatients screened between October 1990 and September 1993 at a community hospital and a university-affiliated hospital, 221 with documented atrial fibrillation were enrolled and followed up for a mean of 27 months. Most (75%) of the patients excluded did not meet the inclusion criteria (because of, for example, an artificial heart valve, mitral stenosis, cardiac transplantation or transient atrial fibrillation); the remainder had not completed enrollment before the end of the study. Following the baseline visit, patients were interviewed by telephone every 6 months, and reported events were confirmed through review of the patients' charts. Hazards for stroke and for stroke and transient ischemic attack (TIA) combined were calculated for each of 4 treatment groups: ASA, warfarin, blended treatment and no treatment, based on the type of anticoagulation therapy patients received during the entire observation period. The blended-treatment group consisted of patients who started on one active therapy and switched to the other or who switched treatments more than once. Corresponding rate ratios (RRs) and 95% confidence intervals (CIs) were calculated with reference to the no-treatment group. Cox proportional hazards analysis was used to adjust for differences in patient characteristics. The rates of bleeding episodes were also analysed. RESULTS: On average, the study patients were older (71.6 [standard deviation 9.3] years) and had a higher prevalence of underlying heart disease (52.0%) than those in the randomized trials. Nineteen patients had a first stroke: 4 in the ASA group, 4 in the warfarin group, 4 in the blended-treatment group and 7 in the no-treatment group, for rates of 5.2, 1.8, 5.3 and 5.9 per 100 person-years, respectively. Only warfarin was associated with a significantly lower risk of stroke compared with no anticoagulant therapy (RR 0.31, 95% CI 0.09-1.00). A similar protective effect of warfarin was found for stroke and TIA combined (2.3 v. 6.7 per 100 person-years; RR 0.34, 95% CI 0.12-0.99); the effect of ASA and blended treatment was not significantly different from no treatment. The rate per 100 person-years of any bleeding was not significantly higher for any treatment group (ASA 2.5, warfarin 3.4 and blended treatment 3.5) compared with the no-treatment group (1.9). Patients receiving warfarin had a significantly greater risk of any bleeding event than patients not receiving anticoagulant therapy (RR 1.79, 95% CI 1.07-3.00). INTERPRETATION: The relative effect of anticoagulant therapy with warfarin in preventing stroke in these practice settings was equivalent to that in the randomized trials, although these patients were older and sicker. This preventive treatment is likely to confer additional benefit as it is more widely prescribed.

Generalizing the results of clinical trials to actual practice: the example of clopidogrel therapy for the prevention of vascular events. CAPRA (CAPRIE Actual Practice Rates Analysis) Study Group. Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events.

PURPOSE: An important element in translating the results obtained in clinical trials of a new treatment to clinical practice is the estimated event rate in patients who would be eligible to receive that treatment. We estimated the effect of clopidogrel, compared with aspirin, in actual practice using the relative risk reduction observed in the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial. SUBJECTS AND METHODS: Ischemic event rates were estimated for 12,931 aspirin users drawn from the Saskatchewan Health population between 1990 and 1995 who had an index diagnosis of myocardial infarction, ischemic stroke, or peripheral arterial disease. To estimate the absolute risk reduction, the 8.7% relative risk reduction from clopidogrel compared with aspirin that was observed in CAPRIE was applied to these rates. RESULTS: The rates of ischemic events were greater in actual practice than among the control patients in the CAPRIE trial. In the Saskatchewan population, patients experienced an outcome event (myocardial infarction, stroke including intracranial hemorrhage, or death) at a rate of 15.9 per 100 patient-years, compared with only 6.9 per 100 patient-years in CAPRIE. If the same 8.7% relative risk reduction seen in the CAPRIE trial is also true for patients seen in routine clinical practice, the greater absolute risk in actual practice would reduce the number needed to treat to prevent one event from 200 patients to 70 patients. CONCLUSION: Absolute risk rates may be substantially greater in clinical practice than in the selected patients enrolled in randomized trials. As a result, similar reductions in relative risk, if true for clinical practice, may yield substantially more benefit in clinical practice than in randomized trials.

The cost of treating heart valve related complications.

BACKGROUND AND AIM OF THE STUDY: Heart valve replacement can result in serious complications. Therefore, it is important in decision making regarding the choice of valves to know the cost of such complications. METHODS: Complications were defined according to guidelines proposed by the Society of Thoracic Surgeons. They included valve thrombosis, embolism, hemorrhage due to anticoagulation, non-structural dysfunction, structural deterioration and endocarditis. The costs of the pre-admission assessment, acute inpatient stay, inpatient physician fees, post-discharge and out-patient physician fees were estimated for each complication to determine the average total cost in 1995 US dollars. Cost inputs were obtained from existing Massachusetts databases and Medicare fee schedules. RESULTS: The costs of managing valve thrombosis, endocarditis and non-structural dysfunction were all estimated to exceed $30,000 for a single event. The costs of acute management of embolism and anticoagulant-related hemorrhage were between $8,000 and $11,500. However, it is of note that managing the sequelae of an embolism was calculated to be greater than $70,000 over 15 years. The greatest contributor to the average cost of treating a complication was determined to be the in-patient facility cost. CONCLUSIONS: Complications related to heart valve replacement can be very costly to manage in both the short term and the long term.

Bileaflet valve replacement: complications and costs.

A meta-analysis of the available literature on the CarboMedics and St. Jude Medical valves was conducted to compare their clinical performance. Frequency of valve-related complications for aortic, mitral, and double-valve replacements served as a measure of performance. An economic model was created to estimate the economic impact of valve-related complications. Overall, fewer events occurred with the St. Jude Medical valve than with the CarboMedics valve. As a result, use of the St. Jude Medical valve is expected to save up to $13,201 over 10 years.