Comparative effectiveness research
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This issue of CHP/PCOR's quarterly newsletter covers news and developments from the spring 2004 quarter.

It features articles about: our new core faculty member Paul Wise, a children's health policy researcher who joins us from Boston University; a survey of patient safety culture now getting underway at hospitals nationwide; CHP/PCOR acting director Doug Owens' research findings on the cost-effectiveness of potential HIV vaccines; a wrap-up of the second annual Health Care Quality and Outcomes Research Conference, where CHP/PCOR faculty and trainees attended and presented research; and new CHP/PCOR assistant director Vandana Sundaram.

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CHP/PCOR
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PURPOSE:

Clopidogrel is more effective than aspirin in preventing recurrent vascular events, but concerns about its cost-effectiveness have limited its use. We evaluated the cost-effectiveness of clopidogrel and aspirin as secondary prevention in patients with a prior myocardial infarction, a prior stroke, or peripheral arterial disease.

METHODS:

We constructed Markov models assuming a societal perspective, and based analyses on the lifetime treatment of a 63-year-old patient facing event probabilities derived from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial as the base case. Outcome measures included costs, life expectancy in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and events averted.

RESULTS:

In patients with peripheral arterial disease, clopidogrel increased life expectancy by 0.55 QALYs at an incremental cost-effectiveness ratio of $25,100 per QALY, as compared with aspirin. In poststroke patients, clopidogrel increased life expectancy by 0.17 QALYs at a cost of $31,200 per QALY. Aspirin was both less expensive and more effective than clopidogrel in post-myocardial infarction patients. In probabilistic sensitivity analyses, our evaluation for patients with peripheral vascular disease was robust. Evaluations of stroke and myocardial infarction patients were sensitive predominantly to the cost and efficacy of clopidogrel, with aspirin therapy more effective and less expensive in 153 of 1000 simulations (15.3%) in poststroke patients and clopidogrel more effective in 119 of 1000 simulations (11.9%) in the myocardial infarction sample.

CONCLUSION:

Clopidogrel provides a substantial increase in quality-adjusted life expectancy at a cost that is within traditional societal limits for patients with either peripheral arterial disease or a recent stroke. Current evidence does not support increased efficacy with clopidogrel relative to aspirin in patients following myocardial infarction.

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American Journal of Medicine
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Douglas K. Owens
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BACKGROUND:

Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model.

METHODS:

Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed.

RESULTS:

For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening.

CONCLUSIONS:

Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio $50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.

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Alimentary Pharmacology & Therapeutics
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Douglas K. Owens
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OBJECTIVES: This study was designed to evaluate the cost-effectiveness of screening patients with a B-type natriuretic peptide (BNP) blood test to identify those with depressed left ventricular systolic function. BACKGROUND: Asymptomatic patients with depressed ejection fraction (EF) may have less progression to heart failure if they can be identified and treated. METHODS: We used a decision model to estimate economic and health outcomes for different screening strategies using BNP and echocardiography to detect left ventricular EF 40% for men and women age 60 years. We used published data from community cohorts (gender-specific BNP test characteristics, prevalence of depressed EF) and randomized trials (benefit from treatment). RESULTS: Screening 1,000 asymptomatic patients with BNP followed by echocardiography in those with an abnormal test increased the lifetime cost of care (176,000 US dollars for men, 101,000 US dollars for women) and improved outcome (7.9 quality-adjusted life years [QALYs] for men, 1.3 QALYs for women), resulting in a cost per QALY of 22,300 US dollars for men and 77,700 US dollars for women. For populations with a prevalence of depressed EF of at least 1%, screening with BNP followed by echocardiography increased outcome at a cost 50,000 US dollars per QALY gained. Screening would not be attractive if a diagnosis of left ventricular dysfunction led to significant decreases in quality of life or income. CONCLUSIONS: Screening populations with a 1% prevalence of reduced EF (men at age 60 years) with BNP followed by echocardiography should provide a health benefit at a cost that is comparable to or less than other accepted health interventions.

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Journal of the American College of Cardiology
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Traditional cost-effectiveness analysis (CEA) assumes that program costs and benefits scale linearly with investment-an unrealistic assumption for epidemic control programs. This paper combines epidemic modeling with optimization techniques to determine the optimal allocation of a limited resource for epidemic control among multiple noninteracting populations. We show that the optimal resource allocation depends on many factors including the size of each population, the state of the epidemic in each population before resources are allocated (e.g. infection prevalence and incidence), the length of the time horizon, and prevention program characteristics. We establish conditions that characterize the optimal solution in certain cases.

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Journal of Health Economics
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One of the important distinctions in methods of measuring health-related quality of life in clinical research is between those that measure health status, on the one hand, and those that measure utility for health states, on the other. Health status measures describe functioning and the impact of illness on one or several aspects of health.

In this chapter, we describe:

Some commonly used health status measures;

The standard utility, or preference-based, measures (also called "health values");

How utilities are used;

Issues that must be addressed in studies using utilities; and

Tools to assist utility assessment.

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National Institutes of Health, Bethesda, Md. in "Symptom Research: Methods and Opportunities, an interactive textbook on clinical symptom research"
Authors
Mary K. Goldstein
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Purpose

To compare the cost-effectiveness of surgical and angioplasty-based coronary artery revascularization techniques, in particular, angioplasty with primary stenting.

Methods

We used data from the Study of Economics and Quality of Life, a substudy of the Bypass Angioplasty Revascularization Investigation (BARI), to measure the outcomes and costs of angioplasty and bypass surgery in patients with multivessel coronary artery disease who had not undergone prior coronary artery revascularization. Using a Markov decision model, we updated the outcomes and costs to reflect technology changes since the time of enrollment in BARI, and projected the lifetime costs and quality-adjusted life-years (QALYs) for the two procedures from the time of initial treatment through death. We accounted for the effects of improved procedural safety and efficiency, and prolonged therapeutic effects of both surgery and stenting. This study was conducted from a societal perspective.

Results

Surgical revascularization was less costly and resulted in better outcomes than catheter-based intervention including stenting. It remained the preferred strategy after adjusting the stent outcomes to eliminate the costs and events associated with target lesion restenosis. Among angioplasty-based strategies, primary stent use cost an additional $189,000 per QALY gained compared with a strategy that reserved stent use for treatment of suboptimal balloon angioplasty results.

Conclusion

Bypass surgery results in better outcomes than angioplasty in patients with multivessel disease, and at a lower cost.

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American Journal of Medicine
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Douglas K. Owens
Mark A. Hlatky
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PURPOSE: To evaluate the cost-effectiveness of recombinant human activated protein C (rhAPC) compared with usual therapy for patients with severe sepsis, and also to determine the influence that severity of illness exerts on cost-effectiveness. MATERIALS AND METHODS: We use a Markov model-based cost-effectiveness analysis of treatment strategies for patients with severe sepsis. Therapy includes treatment with either rhAPC and usual therapy, or usual therapy alone. Probabilities for clinical outcomes were obtained from a large randomized clinical trial comparing the use of rhAPC with placebo (PROWESS study) and from outcomes literature for patients with severe sepsis and its complications. Cost estimates were based on Medicare reimbursement rates, Health Care Financing Administration information and the literature. Outcome measures include life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness. RESULTS: Compared with usual therapy alone, rhAPC treatment for patients with very severe sepsis (APACHE II score > or = 25) was associated with an incremental cost-effectiveness ratio of $13 493/QALY. Treatment of patients with less severe sepsis with rhAPC (APACHE II score 25) had an incremental cost-effectiveness ratio of $403,000/QALY. For patients with very severe sepsis the incremental cost-effectiveness ratio for treatment with rhAPC remained under $30,000/QALY, over a broad range of variables, including costs of rhAPC, costs of acute care and costs and probabilities of complications of treatment. For patients with less severe sepsis, drug costs would need to fall well below current market price before achieving cost-effectiveness. A probabilistic sensitivity analysis comparing rhAPC treatment with usual therapy for patients with very severe sepsis showed that 1% of Monte Carlo simulations had incremental cost-effectiveness ratios > $50,000/QALY. CONCLUSIONS: The use of rhAPC for the treatment of patients with very severe sepsis, as determined by APACHE II score > or = 25, appears cost-effective, while treatment of patients with APACHE II score 25 is not cost-effective.

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Journal of Critical Care
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