Background The objective ci this study woe to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels. Methods We performed a cost-effectiveness analysis based on actual clinical, cost, and health-related quality-of-life data from the Cholesterol and Recurrent Events (CARE) trial. Survival and recurrent coronary heart disease events were modeled from trial data in Markov models, with the use of different assumptions regarding the long-term benefit of therapy. Results Pravastatin therapy increased quality adjusted life expectancy at on incremental cost of $16,000 to $32,000 per quality-adjusted life-year gained. In subgroup analyses, the cost-effectiveness of pravastatin therapy was more favorable for patients >60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels >125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy. Conclusions The cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels compares favorably with other interventions.

Background The objective ci this study woe to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels. Methods We performed a cost-effectiveness analysis based on actual clinical, cos... (more »)

The role of models to support recommendations on the cost-effective use of medical technologies and pharmaceuticals is controversial. At the heart of the controversy is the degree to which experimental or other empirical evidence should be required prior to model use. The controversy stems in part from a misconception that the role of models is to establish truth rather than to guide clinical and policy decisions. In other domains of public policy that involve human life and health, such as environmental protection and defense strategy, models are generally accepted as decision aids, and many models have been formally incorporated into regulatory processes and governmental decision making. We formulate an analytical framework for evaluating the role of models as aids to decision making. Implications for the implementation of Section 114 of the Food and Drug Administration Modernization Act (FDAMA) are derived from this framework.

The role of models to support recommendations on the cost-effective use of medical technologies and pharmaceuticals is controversial. At the heart of the controversy is the degree to which experimental or other empirical evidence should be required p... (more »)

PURPOSE: Homosexual and bisexual men are at an increased risk for human papillomavirus-induced squamous intraepithelial lesions and cancer of the anus. Our objective was to estimate the cost-effectiveness of screening for anal squamous intraepithelial lesions in these high-risk patients. SUBJECTS AND METHODS: A Markov model was developed to evaluate alternative screening strategies using anal cytology in a hypothetical cohort of homosexual and bisexual men, Data were obtained from prospective cohort studies, national databases, Medicare reimbursement rates, and the published literature. Model outcomes included life expectancy, quality-adjusted life expectancy, total lifetime costs, and incremental cost-effectiveness ratios. RESULTS: The undiscounted life expectancy gain associated with anal cytology screening every 3 years was 5.5 months. Compared with no screening, screening every 3 years increased the discounted quality-adjusted life expectancy by 1.8 months and cost $7,000 per quality-adjusted life year (QALY) gained. Screening every 2 years cost $15,100 per QALY gained compared with screening every 3 years. Annual screening provided incremental benefits of less than 0.5 quality-adjusted months and had an incremental cost of $34,800 per QALY gained. Screening every 6 months provided little additional benefit (i.e, 5 days) over that of annual screening and had an incremental cost of $143,500 per QALY gained. CONCLUSION: In homosexual and bisexual men, screening every 2 or 3 years for anal squamous intraepithelial lesions with anal cytology would provide life-expectancy benefits comparable with other accepted preventive health measures, and would be cost-effective. (C) 2000 by Excerpta Medica, Inc.

PURPOSE: Homosexual and bisexual men are at an increased risk for human papillomavirus-induced squamous intraepithelial lesions and cancer of the anus. Our objective was to estimate the cost-effectiveness of screening for anal squamous intraepithelia... (more »)

Purpose. The Hearth Utilities Index (HUI) is a generic, multiattribute, preference-based health-status classification system. The HUI Mark 3 (HUI3) differs from the earlier HUI2 by modifying attributes and allowing more flexibility for capturing high levels of impairment. The authors compared HUI2 and HUI3 scores of patients with Alzheimer's disease (AD) and caregivers, and contrasted results of a cost-effectiveness analysis of new drugs for AD using the two systems. Methods. In a cross-sectional study of 679 AD patient/caregiver pairs. stratified by patient's disease stage (questionable/mild/moderate/severe/profound/terminal) and setting (community/assisted living/nursing home), caregivers completed the combined HUI2/HUI3 questionnaire as proxy respondents for patients and for themselves. Results. Mean (SD) global utility scores for patients were lower on the HUI3 (0.22[0.26]) than on the HUI2 (0.53 [0.21]). Patient HUI3 utility scores ranged from 0.47(0.24) for questionable AD to -0.23 (0.08) for terminal AD, compared with a range of 0.73 (0.15) to 0.14 (0.07) for the HUI2. Among the 203 patients in the severe, profound, and terminal stages, 96 (48%) had negative global HUI3 utility scores, while none had a negative HUI2 score. The utility scores for caregivers were similar on the HUI3 (0.87 [0.14]) and HUI2 (0.87 [0.11]). Cost-effectiveness analysis of a new medication to treat AD showed somewhat more favorable results using the HUI3. Conclusions. The HUI2 and HUI3 discriminate well across AD stages. Compared with the HUI2, the HUI3 yields lower global utility scores for patients with AD, and more scores for states judged worse than dead. The HUI3 may yield substantially different results from the HUI2, particularly for persons who have serious cognitive impairments such as AD.

Purpose. The Hearth Utilities Index (HUI) is a generic, multiattribute, preference-based health-status classification system. The HUI Mark 3 (HUI3) differs from the earlier HUI2 by modifying attributes and allowing more flexibility for capturing high... (more »)

Context Homosexual and bisexual men infected with human immunodeficiency virus (HIV) are at increased risk for human papillomavirus-related anal neoplasia and anal squamous cell carcinoma (SCC). Objective To estimate the clinical benefits and cost-effectiveness of screening HIV-positive homosexual and bisexual men for anal squamous intraepithelial lesions (ASIL) and anal SCC. Design Cost-effectiveness analysis performed from a societal perspective that used reference case recommendations from the Panel on Cost-Effectiveness in Health and Medicine. A state-transition Markov model was developed to calculate lifetime costs, life expectancy, and quality-adjusted life expectancy for no screening vs several screening strategies for ASIL and anal SCC using anal Papanicolaou (Pap) testing at different intervals. Values for incidence, progression, and regression of anal neoplasia; efficacy of screening and treatment; natural history of HIV; health-related quality of life; and costs were obtained from the literature, Setting and Participants Hypothetical cohort of homosexual and bisexual HIV-positive men living in the United States. Main Outcome Measures Life expectancy, quality-adjusted life expectancy, quality-adjusted years of life saved, lifetime costs, and incremental cost-effectiveness ratio. Results Screening for ASIL increased quality-adjusted life expectancy at all stages of HIV disease. Screening with anal Pap tests every 2 years, beginning in early HIV disease (CD4 cell count >0.50 x 10(9)/L), resulted in a 2.7-month gain in quality-adjusted life expectancy for an incremental cost-effectiveness ratio of $13 000 per quality-adjusted life year saved. Screening with anal Pap tests yearly provided additional benefit at an incremental cost of $16 600 per quality-adjusted life year saved. If screening was not initiated until later in the course of HIV disease (CD4 cell count <0.50 x 10(9)/L), then yearly Pap test screening was preferred due to the greater amount of prevalent anal disease (cost-effectiveness ratio of less than $25 000 per quality-adjusted life year saved compared with no screening). Screening every 6 months provided little additional benefit over that of yearly screening. Results were most sensitive to the rate of progression of ASIL to anal SCC and the effectiveness of treatment of precancerous lesions. Conclusions Screening HIV-positive homosexual and bisexual men for ASIL and anal SCC with anal Pap tests offers quality-adjusted life expectancy benefits at a cost comparable with other accepted clinical preventive interventions.

Context Homosexual and bisexual men infected with human immunodeficiency virus (HIV) are at increased risk for human papillomavirus-related anal neoplasia and anal squamous cell carcinoma (SCC). Objective To estimate the clinical benefits and cost-ef... (more »)

Background: Women with HIV infection have a higher risk for cervical squamous intraepithelial lesions than do women without HIV infection, and the optimal regimen for cervical cancer screening in these women is uncertain. Objective: To assess the net health consequences, costs, and cost-effectiveness of Various screening strategies for cervical neoplasia and cancer in HIV-infected women. Design: A cost-effectiveness analysis from a societal perspective done by using a state-transition Markov model. Values for incidence, progression, and regression of cervical neoplasia; efficacy of screening and treatment; progression of HIV disease; mortality from HIV infection and cancer; quality of life; and costs were obtained from the literature. Setting: Simulated clinical practice in the United States. Patients: HIV-infected women representative of the U.S. population. Intervention: Six main screening strategies-no screening, annual Papanicolaou smears, annual Papanicolaou smears after two negative smears obtained 6 months apart (recommended by the Centers for Disease Control and Prevention), semiannual Papanicolaou smears, annual colposcopy, and semiannual colposcopy-were considered. Measurements: Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness. Results: Annual Papanicolaou smear screening resulted in a 2.1-month gain in quality-adjusted life expectancy for an incremental cost of $12 800 per QALY saved. Annual Papanicolaou smear screening after two negative smears obtained 6 months apart provided an additional 0.04 QALYs at a cost of $14 800 per QALY saved. Semiannual Papanicolaou smear screening provided a further 0.17 QALYs at a cost of $27 600 per QALY saved. Annual colposcopy cost more but provided no additional benefit compared with that given by semiannual Papanicolaou smear screening, and semiannual colposcopy exceeded $375 000 per QALY saved. Results were most sensitive to the rate of progression of neoplasia to invasive cancer. Conclusions: in HIV-infected women, cervical cancer screening with annual Papanicolaou smears after two negative smears obtained 6 months apart offers quality-adjusted life expectancy benefits at a cost comparable to that of other clinical preventive interventions.

Background: Women with HIV infection have a higher risk for cervical squamous intraepithelial lesions than do women without HIV infection, and the optimal regimen for cervical cancer screening in these women is uncertain. Objective: To assess the net... (more »)

Context Expert panels and decision-analytic techniques are increasingly used to determine the appropriateness of medical interventions, but these 2 approaches use different methods to process evidence. Objective To compare expert panel appropriateness ratings of coronary angiography after myocardial infarction (from the time of hospital discharge to 12 weeks after infarction) with the health gains and cost-effectiveness predicted by a decision-analytic model. Design Comparison of the degree of importance of the clinical variables considered in expert panel appropriateness ratings vs a previously published decision-analytic model. Identification of 36 clinical scenarios from the expert panel that could be simulated by the decision-analytic model. Main Outcome Measures Appropriateness score and appropriateness classification (expert panel) vs gain in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (decision-analytic model). Results The most important clinical variables were similar in the 2 approaches, with the exercise tolerance test result exerting the greatest leverage on strength of recommendation for angiography. Among the expert panel clinical scenarios considered to be appropriate for coronary angiography that could be simulated in the decision-analysis model, the median (interquartile range) health gain and incremental cost-effectiveness ratio were 0.59 (0.41-0.76) QALYs and $27 000 ($23 000-$35 000) per QALY gained, respectively. Among the clinical scenarios that expert panels considered inappropriate, the corresponding medians (interquartile ranges) were 0.24 (0.19-0.34) QALYs and $54 000 ($36 000-$58 000) per QALY gained. The Spearman rank correlation between appropriateness score and QALY gain was 0.58 (P<.001) and between appropriateness score and estimated incremental cost-effectiveness ratios was -0.66 (P<.001). Conclusions For the 36 expert panel scenarios that could be simulated by the decision; analytic model, there was moderate to good agreement between the appropriateness score and both the health gain and the incremental cost-effectiveness ratio of coronary angiography compared with no angiography in the convalescent phase of acute myocardial infarction, but several scenarios judged as inappropriate by the expert panel approach had cost-effectiveness ratios comparable with many generally recommended medical interventions. Formal synthesis of expert judgment and decision modeling is warranted in future efforts at guideline development.

Context Expert panels and decision-analytic techniques are increasingly used to determine the appropriateness of medical interventions, but these 2 approaches use different methods to process evidence. Objective To compare expert panel appropriatenes... (more »)

Objective: To demonstrate the use of cost-effectiveness analysis to assess the economic impact of donepezil in the treatment of mild or moderate AD. Background: Cost-effectiveness analyses show the relationship between resources used (costs) and health benefits achieved (effects) for an intervention compared with an alternative strategy. Methods: We developed a model to estimate the incremental cost-effectiveness of donepezil compared with no treatment. Ne determined costs per quality-adjusted life-years gained, a measurement that enhances the comparability of diverse studies. The model projects the progression of AD patients into more severe disease stages and into nursing homes, Data from a randomized clinical trial of donepezil were used to assess the drug's impact on the B-week probabilities of progression. Data on the costs and health-related quality of life associated with different disease stages and settings were taken from published estimates and our companion cross-sectional study, respectively. Results: Donepezil costs are partially offset by a reduction in the costs of care due to enhancement in cognitive functioning and the delay to more costly disease stages and settings. The magnitude of this cost offset and of the effect of donepezil on health-related quality of life depends on the model's assumptions about the duration of the drug effect, where controlled data are lacking. If the drug effect exceeds 2 Sears, the model predicts that for mild AD the drug would pay for itself in terms of cost offsets. Conclusions: The results of the cost-effectiveness model presented here suggest that donepezil may be cost-effective but additional controlled data on long-term drug efficacy are needed.

Objective: To demonstrate the use of cost-effectiveness analysis to assess the economic impact of donepezil in the treatment of mild or moderate AD. Background: Cost-effectiveness analyses show the relationship between resources used (costs) and heal... (more »)

Background: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. Objective: To compare early transplantation, delayed transplantation, and no transplantation ?or patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. Design: A Markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. Setting: Therapeutic decision at the time of diagnosis of CML. Patients: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. Intervention: Early transplantation, delayed transplantation, and no transplantation. Measurements: Quality-adjusted, discounted life expectancy. Results: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 5.3 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. Conclusions: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.

Background: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrela... (more »)

Background Coronary angiography is indicated for many patients after acute myocardial infarction (AMI). There are a number of subgroups of AMI patients, however, for whom the indication for coronary angiography is not well established. Methods and Results We developed a decision-analytic model for AMI in representative patient subgroups based on relevant clinical characteristics. The model estimates quality-adjusted life expectancy and direct lifetime costs for two strategies: coronary angiography and treatment guided by its results versus initial medical therapy without angiography. Decision tree chance node probabilities were estimated with the use of pooled data from randomized clinical trials and other relevant literature, costs were estimated with the use of the Medicare Part A database, and quality of life adjustments were derived from a survey of 1051 patients who had had a recent AMI. In our analysis, incremental cost-effectiveness ratios for coronary angiography and treatment guided by its result, compared with initial medical therapy without angiography, ranged between $17 000 and >$1 million per quality-adjusted year of life gained. Patient subgroups with severe postinfarction angina or a strongly positive exercise tolerance test (ETT) typically had cost-effectiveness ratios of <$50 000 per quality-adjusted year of life gained. In addition, most patient subgroups with a prior AMI had cost-effectiveness ratios of <$50 000 per qualify-adjusted year of life gained, even with a negative ETT result. Conclusions In many patient subgroups after AMI, the cost-effectiveness of routine coronary angiography and treatment guided by its results compares favorably with other treatment strategies for coronary heart disease.

Background Coronary angiography is indicated for many patients after acute myocardial infarction (AMI). There are a number of subgroups of AMI patients, however, for whom the indication for coronary angiography is not well established. Methods and Re... (more »)

To assess the health values of patients infected with human immunodeficiency virus (HIV) and examine the relationships between their health values and health status at two points in time, the authors sought to determine whether patients' physical and mental health statuses were good predictors of how they valued their current state of health. One hundred thirty-nine patients with various stages of HIV infection were interviewed in a prospective cohort study based in a primary care practice of a community-based teaching hospital. Patients were interviewed twice at 6-month intervals using three health value measures-the time trade off, rating scale, and Quality of Well-being Scale-and three health status measures: the 18-item Mental Health Inventory, the Dyspnea-Fatigue Index, and the Medical Outcomes Study SF-36 Health Survey. The health status of HIV-infected patients was compromised and, with the exception of mental health, generally was worse among patients with more advanced HIV-infection. Rating scale and Quality of Well-being Scale scores were related inversely to disease stage, but time-trade off scores generally were higher regardless of disease stage. Health value measures showed moderate relationships with measures of physical functioning (r = 0.34 - 0.68) but only a fair relationship with mental health (r = 0.00 - 0.48). The health status of HIV-infected patients who remained asymptomatic or remained symptomatic but without developing acquired immunodeficiency syndrome (AIDS) changed little over 6 months, whereas the health status of patients with AIDS and of patients manifesting progression of HIV-infection deteriorated over time. In contrast, health values, particularly time-tradeoff scores, remained stable even in the face of changes in health status and disease progression. With the exception of mental health, the impact of HIV infection on health status tends to parallel the clinical stage of disease. Health values of HIV-infected patients, however, generally are high and correlate better with physical functioning than with mental health.

To assess the health values of patients infected with human immunodeficiency virus (HIV) and examine the relationships between their health values and health status at two points in time, the authors sought to determine whether patients' physical and... (more »)

Clinical decision models often rely upon survival models predicated on disease-specific hazard functions combined with baseline hazard functions obtained from standard life tables. Two biases may arise in such a modeling process. First, life expectancy estimates may be biased even if estimates of survival probabilities are unbiased (misestimation bias). In simulation studies, the authors discovered that the magnitude of misestimation bias is larger as life expectancy increases, sample size decreases, and censoring percentage increases. In the context of a simple decision analysis, they found that imbalances in the sample sizes for the data used to estimate the parameters among different strategies resulted in nonoptimal decisions in the long run. The second bias stems from misspecification of the survival model itself (misspecification bias). Using a simple cost-effectiveness model, the authors found that-life expectancies and incremental cost-effectiveness ratios differed depending on whether an excess-mortality or a proportional-hazards model was specified. In addition, a predictable pattern was observed for these two survival models when extrapolated to other age and gender groups.

Clinical decision models often rely upon survival models predicated on disease-specific hazard functions combined with baseline hazard functions obtained from standard life tables. Two biases may arise in such a modeling process. First, life expectan... (more »)

Background: Chronic heart failure is associated with a poor prognosis and reduced survival rates. The addition of vasodilator drug therapy to conventional therapy for congestive heart failure has resulted in improved survival. Methods: Adopting a societal viewpoint, we designed a decision analytic model to analyze the costs and effectiveness of three therapies available for the treatment of congestive heart failure: standard therapy (digoxin and diuretic therapy) plus (1) no vasodilator agents, (2) hydralazine hydrochloride-isosorbide dinitrate combination, and (3) enalapril. In addition, we performed sensitivity analyses to determine which model variables were influential in determining incremental cost-effectiveness ratios (cost of drug, cost of hospitalization, efficacy of agents, etc). We used data from three major randomized controlled trials to estimate treatment efficacy, mortality rates, and hospitalization rates. Results: An additional year of life gained by a patient receiving hydralazine-isosorbide combination therapy compared with standard therapy required an additional expense (incremental cost-effectiveness ratio) of $5600. Compared with the hydralazine-isosorbide combination therapy, the incremental cost-effectiveness ratio for enalapril therapy was $9700 per year of life saved. These results were insensitive to wide variations in our baseline assumptions. Conclusions: The cost per year of life saved by vasodilator therapy is much lower than that of other accepted medical therapies. Although the cost per year of life saved for hydralazine-isosorbide combination therapy is lower than that for enalapril therapy, enalapril therapy saves more lives, and the incremental cost of enalapril therapy is justified by the added benefits.

Background: Chronic heart failure is associated with a poor prognosis and reduced survival rates. The addition of vasodilator drug therapy to conventional therapy for congestive heart failure has resulted in improved survival. Methods: Adopting a soc... (more »)