Comparative effectiveness research
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Background Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.

Methods and Findings We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.

Conclusions Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics.

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PLoS Med
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Douglas K. Owens
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Health care costs in the United States are increasing unsustainably, and further efforts to control costs are inevitable and essential. Efforts to control expenditures should focus on the value, in addition to the costs, of health care interventions. Whether an intervention provides high value depends on assessing whether its health benefits justify its costs. High-cost interventions may provide good value because they are highly beneficial; conversely, low-cost interventions may have little or no value if they provide little benefit.

Thus, the challenge becomes determining how to slow the rate of increase in costs while preserving high-value, high-quality care. A first step is to decrease or eliminate care that provides no benefit and may even be harmful. A second step is to provide medical interventions that provide good value: medical benefits that are commensurate with their costs.

This article discusses 3 key concepts for understanding how to assess the value of health care interventions. First, assessing the benefits, harms, and costs of an intervention is essential to understand whether it provides good value. Second, assessing the cost of an intervention should include not only the cost of the intervention itself but also any downstream costs that occur because the intervention was performed. Third, the incremental cost-effectiveness ratio estimates the additional cost required to obtain additional health benefits and provides a key measure of the value of a health care intervention.

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Annals of Internal Medicine
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Douglas K. Owens
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Objective: The World Health Organization (WHO) recently changed its first-line antiretroviral treatment guidelines in resource-limited settings. The cost-effectiveness of the new guidelines is unknown.

Design: Comparative effectiveness and cost-effectiveness analysis using a model of HIV disease progression and treatment.

Methods: Using a simulation of HIV disease and treatment in South Africa, we compared the life expectancy, quality-adjusted life expectancy, lifetime costs, and cost-effectiveness of five initial regimens. Four are currently recommended by the WHO: tenofovir/lamivudine/efavirenz; tenofovir/lamivudine/nevirapine; zidovudine/lamivudine/efavirenz; and zidovudine/lamivudine/nevirapine. The fifth is the most common regimen in current use: stavudine/lamivudine/nevirapine. Virologic suppression and toxicities determine regimen effectiveness and cost-effectiveness.

Results: Choice of first-line regimen is associated with a difference of nearly 12 months of quality-adjusted life expectancy, from 135.2 months (tenofovir/lamivudine/efavirenz) to 123.7 months (stavudine/lamivudine/nevirapine). Stavudine/lamivudine/nevirapine is more costly and less effective than zidovudine/lamivudine/nevirapine. Initiating treatment with a regimen containing tenofovir/lamivudine/nevirapine is associated with an incremental cost-effectiveness ratio of $1045 per quality-adjusted life year compared with zidovudine/lamivudine/nevirapine. Using tenofovir/lamivudine/efavirenz was associated with the highest survival, fewest opportunistic diseases, lowest rate of regimen substitution, and an incremental cost-effectiveness ratio of $5949 per quality-adjusted life year gained compared with tenofovir/lamivudine/nevirapine. Zidovudine/lamivudine/efavirenz was more costly and less effective than tenofovir/lamivudine/nevirapine. Results were sensitive to the rates of toxicities and the disutility associated with each toxicity.

Conclusion: Among the options recommended by WHO, we estimate only three should be considered under normal circumstances. Choice among those depends on available resources and willingness to pay. Stavudine/lamivudine/nevirapine is associated with the poorest quality-adjusted survival and higher costs than zidovudine/lamivudine/nevirapine.

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AIDS (Official Journal of the International AIDS Society)
Authors
Eran Bendavid
Douglas K. Owens
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Abstract

Computed tomographic (CT) angiography is an imaging test that is safer and less expensive than an older test in diagnosing narrowing of the carotid arteries—the most common cause of stroke in US adults. Our examination of Medicare data between 2001 and 2005 found that about 20 percent of the time this test was used, it substituted for the older test. The majority of new use, however, constituted “incremental” use, in cases where patients previously would not have received any test. We found no evidence that the growth in CT angiography led to more patients’ being treated for carotid artery disease. The value of the test as a substitute for the older procedure may be enough to still justify expanding use. Tracking the uses of emerging technologies to encourage efficient use is essential, but it can be challenging in cases where new tools have multiple uses and information is incomplete.

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Health Affairs (Project Hope)
Authors
Laurence C. Baker
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Abstract

BACKGROUND:

Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral therapy (ART) are limited, and all eligible persons are not currently receiving treatment.

OBJECTIVE:

To evaluate the effects on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to reduce risk behavior.

DESIGN:

Dynamic mathematical model of HIV transmission and disease progression and cost-effectiveness analysis.

DATA SOURCES:

Published literature.

TARGET POPULATION:

High-risk (injection drug users and men who have sex with men) and low-risk persons aged 15 to 64 years in the United States.

TIME HORIZON:

Twenty years and lifetime (costs and quality-adjusted life-years [QALYs]).

PERSPECTIVE:

Societal.

INTERVENTION:

Expanded HIV screening and counseling, treatment with ART, or both.

OUTCOME MEASURES:

New HIV infections, discounted costs and QALYs, and incremental cost-effectiveness ratios.

RESULTS OF BASE-CASE ANALYSIS:

One-time HIV screening of low-risk persons coupled with annual screening of high-risk persons could prevent 6.7% of a projected 1.23 million new infections and cost $22,382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART utilization to 75% of eligible persons prevents 10.3% of infections and costs $20,300 per QALY gained. A combination strategy prevents 17.3% of infections and costs $21,580 per QALY gained.

RESULTS OF SENSITIVITY ANALYSIS:

With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4 count is greater than 0.350 × 10(9) cells/L prevents 20% to 28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%.

LIMITATION:

The model of disease progression and treatment was simplified, and acute HIV screening was excluded.

CONCLUSION:

Expanding HIV screening and treatment simultaneously offers the greatest health benefit and is cost-effective. However, even substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U.S. HIV epidemic without substantial reductions in risk behavior.

PRIMARY FUNDING SOURCE:

National Institute on Drug Abuse, National Institutes of Health, and Department of Veterans Affairs.

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Annals of Internal Medicine,
Authors
Douglas K. Owens
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Abstract

Liver disease and liver cancer associated with childhood-acquired chronic hepatitis B are leading causes of death among adults in China. Despite expanded newborn hepatitis B vaccination programs, approximately 20% of children under age 5 years and 40% of children aged 5 to 19 years remain unprotected from hepatitis B. Although immunizing them will be beneficial, no studies have examined the cost-effectiveness of hepatitis B catch-up vaccination in an endemic country like China. We examined the cost-effectiveness of a hypothetical nationwide free hepatitis B catch-up vaccination program in China for unvaccinated children and adolescents aged 1 to 19 years. We used a Markov model for disease progression and infections. Cost variables were based on data published by the Chinese Ministry of Health, peer-reviewed Chinese and English publications, and the GAVI Alliance. We measured costs (2008 U.S. dollars and Chinese renminbi), quality-adjusted life years, and incremental cost-effectiveness from a societal perspective. Our results show that hepatitis B catch-up vaccination for children and adolescents in China is cost-saving across a range of parameters, even for adolescents aged 15 to 19 years old. We estimate that if all 150 million susceptible children under 19 were vaccinated, more than 8 million infections and 65,000 deaths due to hepatitis B would be prevented. CONCLUSION: The adoption of a nationwide free catch-up hepatitis B vaccination program for unvaccinated children and adolescents in China, in addition to ongoing efforts to improve birth dose and newborn vaccination coverage, will be cost-saving and can generate significant population-wide health benefits. The success of such a program in China could serve as a model for other endemic countries.

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Hepatology
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Abstract

STUDY OBJECTIVE:

Symptoms associated with pulmonary embolism can be nonspecific and similar to many competing diagnoses, leading to excessive costly testing and treatment, as well as missed diagnoses. Objective studies are essential for diagnosis. This study evaluates the cost-effectiveness of different diagnostic strategies in an emergency department (ED) for patients presenting with undifferentiated symptoms suggestive of pulmonary embolism.

METHODS:

Using a probabilistic decision model, we evaluated the incremental costs and effectiveness (quality-adjusted life-years gained) of 60 testing strategies for 5 patient pretest categories (distinguished by Wells score [high, moderate, or low] and whether deep venous thrombosis is clinically suspected). We performed deterministic and probabilistic sensitivity analyses.

RESULTS:

In the base case, for all patient pretest categories, the most cost-effective diagnostic strategy is to use an initial enzyme-linked immunosorbent assay D-dimer test, followed by compression ultrasonography of the lower extremities if the D-dimer is above a specified cutoff. The level of the preferred cutoff varies with the Wells pretest category and whether a deep venous thrombosis is clinically suspected. D-dimer cutoffs higher than the current recommended cutoff were often preferred for patients with even moderate and high Wells categories. Compression ultrasonography accuracy had to decrease below commonly cited levels in the literature before it was not part of a preferred strategy.

CONCLUSION:

When pulmonary embolism is suspected in the ED, use of an enzyme-linked immunosorbent assay D-dimer assay, often at cutoffs higher than those currently in use (for patients in whom deep venous thrombosis is not clinically suspected), followed by compression ultrasonography as appropriate, can reduce costs and improve outcomes.

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Annals of Emergency Medicine
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Comparative effectiveness research (CER) has the potential to slow health care spending growth by focusing resources on health interventions that provide the most value. In this article, we discuss issues surrounding CER and its implementation and apply these methods to a salient clinical example: treatment of prostate cancer. Physicians have several options for treating patients recently diagnosed with localized disease, including removal of the prostate (radical prostatectomy), treatment with radioactive seeds (brachytherapy), radiation therapy (IMRT), or-if none of these are pursued- active surveillance. Using a commercial health insurance claims database and after adjustment for comorbid conditions, we estimate that the additional cost of treatment with radical prostatectomy is $7,300, while other alternatives are more expensive-$19,000 for brachytherapy and $46,900 for IMRT. However, a review of the clinical literature uncovers no evidence that justifi es the use of these more expensive approaches. These results imply that if patient management strategies were shifted to those supported by CER-based criteria, an estimated $1.7 to $3.0 billion (2009 present value) could be saved each year.

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Demography
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Liver disease and liver cancer associated with childhood-acquired chronic hepatitis B are
leading causes of death among adults in China. Despite expanded newborn hepatitis B
vaccination programs, approximately 20% of children under age 5 years and 40% of children aged 5 to 19 years remain unprotected from hepatitis B. Although immunizing them will be beneficial, no studies have examined the cost-effectiveness of hepatitis B catch-up vaccination in an endemic country like China. We examined the cost-effectiveness of a hypothetical nationwide free hepatitis B catch-up vaccination program in China for unvaccinated children and adolescents aged 1 to 19 years. We used a Markov model for disease progression and infections. Cost variables were based on data published by the Chinese Ministry of Health, peer-reviewed Chinese and English publications, and the GAVI Alliance.


We measured costs (2008 U.S. dollars and Chinese renminbi), quality-adjusted life years,and incremental cost-effectiveness from a societal perspective. Our results show that hepatitis B catch-up vaccination for children and adolescents in China is cost-saving across a range of parameters, even for adolescents aged 15 to 19 years old. We estimate that if all 150 million susceptible children under 19 were vaccinated, more than 8 million infections and 65,000 deaths due to hepatitis B would be prevented. Conclusion: The adoption of a nationwide free catch-up hepatitis B vaccination program for unvaccinated children and adolescents in China, in addition to ongoing efforts to improve birth dose and newborn vaccination coverage, will be cost-saving and can generate significant population-wide health benefits. The success of such a program in China could serve as a model for other endemic countries.

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Hepatology
Authors
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Background: Although recent guidelines call for expanded routine screening for HIV, resources for antiretroviral therapy (ART) are limited, and all eligible persons are not currently receiving treatment.

Objective: To evaluate the effects on the U.S. HIV epidemic of expanded ART, HIV screening, or interventions to reduce risk behavior.

Design: Dynamic mathematical model of HIV transmission and disease progression and cost-effectiveness analysis.

Data Sources: Published literature.

Target Population: High-risk (injection drug users and men who have sex with men) and low-risk persons aged 15 to 64 years in the United States.

Time Horizon: Twenty years and lifetime (costs and quality-adjusted life-years [QALYs]).

Perspective: Societal.

Intervention: Expanded HIV screening and counseling, treatment with ART, or both.

Outcome Measures: New HIV infections, discounted costs and QALYs, and incremental cost-effectiveness ratios.

Results of Base-Case Analysis: One-time HIV screening of low-risk persons coupled with annual screening of high-risk persons could prevent 6.7% of a projected 1.23 million new infections and cost $22 382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART utilization to 75% of eligible persons prevents 10.3% of infections and costs $20 300 per QALY gained. A combination strategy prevents 17.3% of infections and costs $21 580 per QALY gained.

Results of Sensitivity Analysis: With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4 count is greater than 0.350 × 109 cells/L prevents 20% to 28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%.

Limitation: The model of disease progression and treatment was simplified, and acute HIV screening was excluded.

Conclusion: Expanding HIV screening and treatment simultaneously offers the greatest health benefit and is cost-effective. However, even substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U.S. HIV epidemic without substantial reductions in risk behavior.

Primary Funding Source: National Institute on Drug Abuse, National Institutes of Health, and Department of Veterans Affairs.

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Annals of Internal Medicine
Authors
Douglas K. Owens
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