Cost-effectiveness analysis of potential improvements to emergency medical services for victims of out-of-hospital cardiac arrest

STUDY OBJECTIVE: To measure the incremental cost-effectiveness of various improvements to emergency medical services (EMS) systems aimed at increasing survival after out-of-hospital cardiac arrest. METHODS: We performed cost-effectiveness analysis based on (1) metaanalysis of effectiveness of the various EMS systems, (2) costing of each component of EMS systems, (3) modeling of the relationship between the proportion of cardiac arrest victims who receive CPR and the proportion of individuals trained, (4) modeling of the relationship between response time interval and the characteristics of the EMS system, (5) measurement of quality of life, and (6) decision analysis to combine the results of the first five components. RESULTS: The incremental cost-effectiveness ratio for a 48-second improvement in mean response time in a one-tier EMS system yielded by the addition of more EMS providers was $368,000 per quality-adjusted life year (QALY). For improved response time in a two-tier EMS system by the addition of more basic life support (BLS)/BLS-defibrillator (BLS-D) providers to the first tier, the ratio was $53,000 per QALY with pump vehicles or $159,000 per QALY with ambulances. Change from a one-tier EMS to a two-tier EMS system by the addition of initial BLS/BLS-D providers in pump vehicles as the first tier was associated with a cost per QALY of $40,000. Change from one-tier EMS to two-tier EMS by the addition of initial BLS/BLS-D providers in ambulances as the first tier was associated with a cost per QALY of $94,000. CONCLUSION: The most attractive options in terms of incremental cost-effectiveness were improved response time in a two-tier EMS system or change from a one-tier to a two-tier EMS system. Future research should be directed toward identification of the costs of instituting the first tier of a two-tier EMS system and identification of cost-effective methods of improving response time.     

Projected cost-effectiveness of primary angioplasty for acute myocardial infarction

OBJECTIVES: This study sought to evaluate the cost-effectiveness of primary angioplasty for acute myocardial infarction under varying assumptions about effectiveness, existing facilities and staffing and volume of services. BACKGROUND: Primary angioplasty for acute myocardial infarction has reduced mortality in some studies, but its actual effectiveness may vary, and most U.S. hospitals do not have cardiac catheterization laboratories. Projections of cost-effectiveness in various settings are needed for decisions about adoption. METHODS: We created a decision analytic model to compare three policies: primary angioplasty, intravenous thrombolysis and no intervention. Probabilities of health outcomes were taken from randomized trials (base case efficacy assumptions) and community-based studies (effectiveness assumptions). The base case analysis assumed that a hospital with an existing laboratory with night/weekend staffing coverage admitted 200 patients with a myocardial infarction annually. In alternative scenarios, a new laboratory was built, and its capacity for elective procedures was either 1) needed or 2) redundant with existing laboratories. RESULTS: Under base case efficacy assumptions, primary angioplasty resulted in cost savings compared with thrombolysis and had a cost of $12,000/quality-adjusted life-year (QALY) saved compared with no intervention. In sensitivity analyses, when there was an existing cardiac catheterization laboratory at a hospital with > or = 200 patients with a myocardial infarction annually, primary angioplasty had a cost of < $30,000/QALY saved under a wide range of assumptions. However, the cost/QALY saved increased sharply under effectiveness assumptions when the hospital had < 150 patients with a myocardial infarction annually or when a redundant laboratory was built. CONCLUSIONS: At hospitals with an existing cardiac catheterization laboratory, primary angioplasty for acute myocardial infarction would be cost-effective relative to other medical interventions under a wide range of assumptions. The procedure's relative cost-ineffectiveness at low volumes or redundant laboratories supports regionalization of cardiac services in urban areas. However, approaches to overcoming competitive barriers and close monitoring of outcomes and costs will be needed.     

Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model

BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.     

Cost-effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age

BACKGROUND: Screening mammography is recommended for women 50 to 69 years of age because of its proven efficacy and reasonable cost-effectiveness. Extending screening recommendations to include women 40 to 49 years of age remains controversial. OBJECTIVE: To compare the cost-effectiveness of screening mammography in women of different age groups. DESIGN: Cost-effectiveness analysis done using Markov and Monte Carlo models. PATIENTS: General population of women 40 years of age and older. INTERVENTIONS: Biennial screening from 50 to 69 years of age was compared with no screening. Screening done every 18 months from ages 40 to 49 years, followed by biennial screening from ages 50 to 69 years, was compared with biennial screening from ages 50 to 69 years. MEASUREMENTS: Life-expectancy, costs, and incremental cost-effectiveness. RESULTS: Screening women from 50 to 69 years of age improved life expectancy by 12 days at a cost of $704 per woman, resulting in a cost-effectiveness ratio of $21,400 per year of life saved. Extending screening to include women 40 to 49 years of age improved life expectancy by 2.5 days at a cost of $676 per woman. The incremental cost-effectiveness of screening women 40 to 49 years of age was $105,000 per year of life saved. On the basis of a multiway sensitivity analysis, there is a 75% chance that screening mammography in women 50 to 69 years of age costs less than $50,000 per year of life saved, compared with a 7% chance in women 40 to 49 years of age. CONCLUSION: The cost-effectiveness of screening mammography in women 40 to 49 years of age is almost five times that in older women. When breast cancer screening policies are being set, the incremental cost-effectiveness of extending mammographic screening to younger women should be considered.     

The cost-effectiveness of air bags by seating position

CONTEXT: Motor vehicle crashes continue to cause significant mortality and morbidity in the United States. Installation of air bags in new passenger vehicles is a major initiative in the field of injury prevention. OBJECTIVE: To assess the net health consequences and cost-effectiveness of driver's side and front passenger air bags from a societal perspective, taking into account the increased risk to children who occupy the front passenger seat and the diminished effectiveness for older adults. DESIGN: A deterministic state transition model tracked a hypothetical cohort of new vehicles over a 20-year period for 3 strategies: (1) installation of safety belts, (2) installation of driver's side air bags in addition to safety belts, and (3) installation of front passenger air bags in addition to safety belts and driver's side air bags. Changes in health outcomes, valued in terms of quality-adjusted life-years (QALYs) and costs (in 1993 dollars), were projected following the recommendations of the Panel on Cost-effectiveness in Health and Medicine. PARTICIPANTS: US population-based and convenience sample data were used. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratios. RESULTS: Safety belts are cost saving, even at 50% use. The addition of driver's side air bags to safety belts results in net health benefits at an incremental cost of $24000 per QALY saved. The further addition of front passenger air bags results in an incremental net benefit at a higher incremental cost of $61000 per QALY saved. Results were sensitive to the unit cost of air bag systems, their effectiveness, baseline fatality rates, the ratio of injuries to fatalities, and the real discount rate. CONCLUSIONS: Both air bag systems save life-years at costs that are comparable to many medical and public health practices. Immediate steps can be taken to enhance the cost-effectiveness of front passenger air bags, such as moving children to the rear seat.     

The cost-effectiveness of routine postoperative radiotherapy after sector resection and axillary dissection for breast cancer stage I. Results from a randomized trial

BACKGROUND: Cost-effectiveness of routine postoperative radiotherapy after breast-conserving surgery has not been prospectively evaluated earlier. In times of rationing of medical resources, valid assessments of cost-effectiveness are important for rational allocation of resources. PURPOSE: Cost and cost-effectiveness of routine postoperative radiotherapy was calculated in a prospective randomized trial comparing sector resection plus axillary dissection with (XRT group) or without (non-XRT group) postoperative radiotherapy in breast cancer stage I. Three hundred eighty-one patients were included. After a median follow-up of five years 43 local recurrences, six of them in the XRT-group occurred (P < 0.0001). No difference in regional and distant recurrence (P = 0.23) or survival (P = 0.44) was observed. PATIENTS AND METHODS: Direct medical costs as well as indirect costs in terms of production lost during the treatment period and travel expenses were estimated from data in the medical records and the national insurance registry of each patient. Average costs of different treatment activities and measures were estimated for the XRT-group and the non-XRT group respectively. From these estimates differences in costs and effectiveness between the groups were calculated and marginal cost-effectiveness ratios were estimated. For the construction of QALYs each life-year was quality-adjusted by a utility value depending on which health state the patient was considered to perceive. RESULTS: Taking into account the cost of primary treatment, the cost of follow-up, the cost of treatment of a local recurrence, travel expenses and indirect costs (production lost) excluding costs for treatment of regional and distant recurrence the cost per avoided local recurrence at five years was SEK 337,727 ($44,438, Pounds 27,018). Adjustment for quality of life showed a cost for every gained QALY to be SEK approximately 1.6 million, ($210,526, Pounds 128,000), range SEK 0.2-3.9 million ($26,315-513,158, Pounds 16,000-312,000). CONCLUSION: The cost of routine postoperative radiotherapy after sector resection and axillary dissection in breast cancer stage I per avoided local recurrence and gained QALY is high. The cost per gained QALY show great variation depending on utility value, which in this study was derived from external observers and not from the patients themselves. These results stress the importance of identifying risk factors for local recurrence, better understanding of impact on quality of life of a local recurrence and adding cost evaluations to clinical trials in early breast cancer.     

Cost-effectiveness of HIV-prevention skills training for men who have sex with men

OBJECTIVE: A previous study empirically compared the effects of two HIV-prevention interventions for men who have sex with men: (i) a safer sex lecture, and (ii) the same lecture coupled with a 1.5 h skills-training group session. The skills-training intervention led to a significant increase in condom use at 12-month follow-up, compared with the lecture-only condition. The current study retrospectively assesses the incremental cost-effectiveness of skills training to determine whether it is worth the extra cost to add this component to an HIV-prevention intervention that would otherwise consist of a safer sex lecture only. DESIGN: Standard techniques of incremental cost-utility analysis were employed. METHODS: A societal perspective and a 5% discount rate were used. Cost categories assessed included: staff salary, fringe benefits, quality assurance, session materials, client transportation, client time valuation, and costs shared with other programs. A Bernoulli-process model of HIV transmission was used to estimate the number of HIV infections averted by the skills-training intervention component. For each infection averted, the discounted medical costs and quality-adjusted life years (QALY) saved were estimated. One- and multi-way sensitivity analyses were performed to assess the robustness of base-case results to changes in modeling assumptions. RESULTS: Under base-case assumptions, the incremental cost of the skills training was less than $13,000 (or about $40 per person). The discounted medical costs averted by incrementally preventing HIV infections were over $170,000; more than 21 discounted QALY were saved. The cost per QALY saved was negative, indicating cost-savings. These results are robust to changes in most modeling assumptions. However, the model is moderately sensitive to changes in the per-contact risk of HIV transmission. CONCLUSIONS: Under most reasonable assumptions, the incremental costs of the skills training were outweighed by the medical costs saved. Thus, not only is skills training effective in reducing risky behavior, it is also cost-saving.     

Cost-effectiveness model of adjunctive lamotrigine for the treatment of epilepsy

OBJECTIVE: To predict the cost-effectiveness of lamotrigine by evaluating the costs and health outcomes in treated patients. BACKGROUND: Lamotrigine adjunctive therapy has been found to be associated with decreased seizure frequency and severity in patients who are refractory to treatment with the older antiepileptic drugs (AEDs). METHODS: We used a cost-effectiveness clinical decision analysis framework to assess the impact of these clinical benefits on patient health care use. The measure of effectiveness was seizure-free days gained. The measures of health care resource use included hospitalizations, outpatient and emergency department visits, surgery, and AEDs. Medical care use and cost estimates were derived from clinical trial data and published sources. Costs and effectiveness (incremental costs per seizure-free days gained) of lamotrigine adjunctive therapy versus older AEDs were compared in patients refractory to previous treatment during three time periods: the start-up year, the second year when decisions about surgery were made, and all subsequent years. RESULTS AND CONCLUSIONS: The model predicts that use of lamotrigine would be associated with an overall reduction in use of other direct medical care resources (hospitalizations, outpatient visits, diagnostic and laboratory tests, and surgery). For a 10-year time horizon, the estimated cost-effectiveness ratio is $6.9 per seizure-free day gained. The model provides a flexible framework to analyze the effect of new antiepileptic drugs.     

Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. NINDS rt-PA Stroke Study Group

Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.     

Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets

BACKGROUND: This study augments a randomized controlled trial to analyze the cost-effectiveness of 2 standardized treatments for major depression relative to each other and to the "usual care" provided by primary care physicians. METHODS: A randomized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy (where nortriptyline hydrochloride was given) or interpersonal psychotherapy provided in a standardized framework or a primary physician's usual care. Two outcome measures, depression-free days and quality-adjusted days, were developed using information on depressive symptoms over time. The costs of care were calculated. Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated. Sensitivity analyses were performed. RESULTS: In terms of both economic costs and quality-of-life outcomes, patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy. Both standardized therapies provided better outcomes than primary physician's usual care, but each consumed more resources. No meaningful cost-offsets were found. The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $12.66 to $16.87 which translates to direct cost per quality-adjusted year gained from $11270 to $19510. CONCLUSIONS: Standardized treatments for depression lead to better outcomes than usual care but also lead to higher costs. However, the estimates of the cost per quality-of-life year gained for standardized pharmacotherapy are comparable with those found for other treatments provided in routine practice.     

Bootstrap estimates of standard errors in validity generalization.

Bootstrapping is introduced as a method for approximating the standard errors of validity generalization (VG) estimates. A Monte Carlo study was conducted to evaluate the accuracy of bootstrap validity-distribution parameter estimates, bootstrap standard error estimates, and nonparametric bootstrap confidence intervals. In the simulation study the authors manipulated the sample sizes per correlation coefficient, the number of coefficients per VG analysis, and the variance of the distribution of true correlation coefficients. The results indicate that the standard error estimates produced by the bootstrapping procedure were very accurate. It is recommended that the bootstrap standard-error estimates and confidence intervals be used in the interpretation of the results of VG analyses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cost-effectiveness of guided self-help treatment for recurrent binge eating.

Objective: Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive–behavioral therapy guided self-help intervention (CBT–GSH) to treat recurrent binge eating compared to treatment as usual (TAU). Method: Participants were 123 adult members of an HMO (mean age = 37.2 years, 91.9% female, 96.7% non-Hispanic White) who met criteria for eating disorders involving binge eating as measured by the Eating Disorder Examination (C. G. Fairburn & Z. Cooper, 1993). Participants were randomized either to treatment as usual (TAU) or to TAU plus CBT–GSH. The clinical outcomes were binge-free days and quality-adjusted life years (QALYs); total societal cost was estimated using costs to patients and the health plan and related costs. Results: Compared to those receiving TAU only, those who received TAU plus CBT–GSH experienced 25.2 more binge-free days and had lower total societal costs of $427 over 12 months following the intervention (incremental CEA ratio of ?$20.23 per binge-free day or ?$26,847 per QALY). Lower costs in the TAU plus CBT–GSH group were due to reduced use of TAU services in that group, resulting in lower net costs for the TAU plus CBT group despite the additional cost of CBT–GSH. Conclusions: Findings support CBT–GSH dissemination for recurrent binge-eating treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Economic and policy implications of adopting paclitaxel as first-line therapy for advanced ovarian cancer: an Ontario perspective

PURPOSE: To determine the potential economic and policy implications that result from incorporating paclitaxel into first-line therapy for stage 3 and 4 ovarian cancer patients in the province of Ontario, Canada. METHODS: A cost-effectiveness analysis was conducted to compare cisplatin/cyclophosphamide (CC), a standard therapy, with cisplatin/paclitaxel (CT). Based on survival curves from a clinical trial, mean costs and survival were calculated. Sensitivity analyses were conducted based on altering the duration of paclitaxel infusion, discount rates, and efficacy of paclitaxel. RESULTS: The mean survival duration is prolonged from 2.06 years with the standard therapy to 2.44 years with the paclitaxel combination. The paclitaxel therapy is more expensive, with a mean cost of $17,469 (Canadian) per patient treated with CT compared with $5,228 per patient with CC. The incremental cost-effectiveness ratio is $32,213 per year gained. Sensitivity analyses show that the conclusions remain unchanged. The use of CT as first-line treatment for advanced ovarian cancer patients in Ontario requires an additional $9 million per year over and above the present costs to treat this patient population. CONCLUSION: Although paclitaxel-based therapy prolongs survival, it comes at an increased cost. It may not be possible to fund paclitaxel treatment using resources presently allocated to first-line chemotherapy for advanced ovarian cancer. The policy implications for absorbing the cost of paclitaxel in the context of a publicly funded health care system are discussed.     

Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation

OBJECTIVE: To examine the conditions necessary to make screening for microalbuminuria in patients with insulin dependent diabetes mellitus cost effective. DESIGN: This economic evaluation compared two strategies designed to prevent the development of end stage renal disease in patients with insulin dependent diabetes with disease for five years. Strategy A, screening for microalbuminuria as currently recommended, was compared with strategy B, a protocol in which patients were screened for hypertension and macroproteinuria. INTERVENTION: Patients identified in both strategies were treated with an angiotensin converting enzyme inhibitor. SETTING: Computer simulation. MAIN OUTCOME MEASURES: Strategy costs and quality adjusted life years (QALYs). RESULTS: The model predicted that strategy A would produce an additional 0.00967 QALYs at a present value cost of $261.53 (1990 US$) per patient (or an incremental cost/QALY of $27,041.69) over strategy B. The incremental cost/QALY for strategy A over B was sensitive to several variables. If the positive predictive value of screening for microalbuminuria (impact of false label and unnecessary treatment) is < 0.72, the effect of treatment to delay progression from microalbuminuria to macroproteinuria is < 1.6 years, the cumulative incidence of diabetic nephropathy falls to < 20%, or > 64% of patients demonstrate hypertension at the onset of microalbuminuria, then the incremental costs/QALY will exceed $75,000. CONCLUSION: Whether microalbuminuria surveillance in this population is cost effective requires more information. Being aware of the costs, recommendation pitfalls, and gaps in our knowledge should help focus our efforts to provide cost effective care to this population.     

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.     

Neural Network Embedded Monte Carlo Approach for Water Quality Modeling under Input Information Uncertainty

This paper proposes a neural network embedded Monte Carlo (NNMC) approach to account for uncertainty in water quality modeling. The framework of the proposed method has three major parts: a numerical water quality model, a neural network technique, and Monte Carlo simulation. The numerical model is used to generate desirable output for training and testing sets, and the neural network is used as a universal functional mapping tool to approximate the input-output response of the numerical model. The Monte Carlo simulation then uses the neural network to generate numerical realizations based on a probabilistic distribution of parameters, thus obtaining a probabilistic distribution of the simulated state variables. By embedding a neural network into the conventional Monte Carlo simulation, the proposed approach significantly improves upon the conventional method in computational efficiency. The proposed approach has been applied to uncertainty and risk analyses of a phosphorus model for Triadelphia Reservoir in Maryland. The results of this research show that the NNMC approach has potential for efficient uncertainty analysis of water quality modeling.     

Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. The Osservatorio SIFO sui Farmaci

OBJECTIVE: This study was undertaken to evaluate the cost and the effectiveness of zidovudine monotherapy in patients with advanced HIV infection and to derive preliminary data on the cost-effectiveness of the triple treatment with saquinavir plus zalcitabine plus zidovudine compared with zidovudine alone. DESIGN: We used a combined method of survival analysis utilizing both the quality-adjusted time without symptoms or toxicity (Q-TWIST) method and the Gompertz approach. This combined method was applied to assess the absolute cost-effectiveness and cost-utility ratios of zidovudine monotherapy and to perform a preliminary incremental cost-effectiveness comparison of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone. The clinical material used in our study was derived from two reports on the treatment of advanced HIV infection. Data of lifetime costs of HIV infection were obtained from published information. RESULTS: In patients with advanced HIV infection treated with zidovudine monotherapy, lifetime survival was 252.1 discounted person-years per 100 patients. Using an average lifetime cost of $93,000 (discounted) per individual, the absolute ratio of cost-effectiveness for zidovudine monotherapy was $36,980 per life-year, while the absolute cost-utility ratio was $47,112 per quality-adjusted life-year. In the comparative analysis of saquinavir plus zalcitabine plus zidovudine versus zidovudine alone, our calculations showed that the administration of the triple treatment can have an "average" cost-effectiveness, provided that mean lifetime survival per patient (discounted) is improved to at least 3.68 years (with an average survival gain of at least 14 mo per patient). CONCLUSIONS: The values of absolute cost-effectiveness and cost-utility ratios for zidovudine monotherapy are a useful reference point for further pharmacoeconomic studies in the area of antiretroviral drugs.     

The cost effectiveness of alpha interferon in the treatment of chronic active hepatitis C

OBJECTIVE: To model the costs and effects of alpha interferon in the treatment of chronic active hepatitis C. DESIGN: A Markov modelling process to simulate the costs and outcomes in hypothetical cohorts of patients treated with and without alpha interferon. OUTCOME MEASURES: Costs per life saved and per life-year gained. RESULTS: On the basis of assumptions formulated about the disease processes and response to treatment, treatment with alpha interferon results in a discounted cost per life-year gained of $33,230 in patients with cirrhosis at the start of treatment and $71,950 in patients without advanced liver disease. The result is sensitive to the assumptions made about the long term effectiveness of alpha interferon. CONCLUSIONS: Alpha interferon is an expensive drug. Its effectiveness is clouded by uncertainty about the long term impact of the drug on the natural history of the disease. If adopted, its use should be monitored to allow the long term cost effectiveness of the drug to be evaluated properly.