Comparative effectiveness: its role in the healthcare system.

PURPOSE OF REVIEW: To describe comparative effectiveness and assess its role in crafting new healthcare policy. RECENT FINDINGS: Senate Bill S.3408 would establish a nongovernment-affiliated Healthcare Comparative Effectiveness Research Institute that would work with healthcare experts and stakeholders in healthcare to prioritize interventions and services to be studied. A value-based medicine system of standardized comparative effectiveness and cost-effectiveness data using utilities would allow physicians to assess the total value (improvement in quality of life and/or length of life) conferred by interventions. SUMMARY: Standardized comparativeness and cost-effectiveness data will give physicians an information system to identify the interventions that confer the greatest value to patients, and thus deliver higher quality care than possible with evidence-based data alone while allowing the most cost-effective care.

A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration.

OBJECTIVE: To assess the conferred value and average cost-utility (cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD). DESIGN: Value-based medicine cost-utility analysis. PARTICIPANTS: MARINA (Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD) Study patients utilizing published primary data. METHODS: Reference case, third-party insurer perspective, cost-utility analysis using 2006 United States dollars. MAIN OUTCOME MEASURES: Conferred value in the forms of (1) quality-adjusted life-years (QALYs) and (2) percent improvement in health-related quality of life. Cost-utility is expressed in terms of dollars expended per QALY gained. All outcomes are discounted at a 3% annual rate, as recommended by the Panel on Cost-effectiveness in Health and Medicine. Data are presented for the second-eye model, first-eye model, and combined model. RESULTS: Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization. The reference case treatment cost is $52652, and the cost-utility for the second-eye model is $50691/QALY. The quality-of-life gain from the first-eye model is 6.4% and the cost-utility is $123887, whereas the most clinically simulating combined model yields a quality-of-life gain of 10.4% and cost-utility of $74169. CONCLUSIONS: By conventional standards and the most commonly used second-eye and combined models, intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in randomized clinical trials.

The comparative effectiveness and cost-effectiveness of vitreoretinal interventions.

PURPOSE OF REVIEW: The comparative effectiveness of medical interventions has recently been emphasized in the literature, typically for interventions in a similar class. Value-based medicine, the practice of medicine based on the value (improvement in quality of life and/or length of life) conferred by medical interventions, allows a measure of comparative effectiveness of interventions across all of health care, no matter how disparate. This report discusses recent comparative effectiveness studies in the vitreoretinal literature. RECENT FINDINGS: Vitreoretinal interventions have good to excellent comparative effectiveness compared with commonly utilized interventions across health care, such as treatment for osteoporosis and hyperlipidemia. They also tend to be cost-effective when an upper limit of $100 000/quality-adjusted life-year is utilized. SUMMARY: Value can be measured using either or both of two outcomes - the quality-adjusted life-year gain and/or the percentage improvement in value - both of which allow for an evaluation of comparative effectiveness, which can be compared on the same scale for every intervention. This value can also be integrated with costs using the outcome of dollars expended per quality-adjusted life-year ($/quality-adjusted life-year, or the cost-utility ratio), which allows a comparison of cost-effectiveness across all interventions. The majority of vitreoretinal interventions confer considerable value and are cost-effective.

A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration.

OBJECTIVE: To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization. DESIGN: Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria. PARTICIPANTS: Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study. METHODS: Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate. MAIN OUTCOME MEASURES: Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained. RESULTS: Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness. CONCLUSIONS: Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

Value-based medicine, comparative effectiveness, and cost-effectiveness analysis of topical cyclosporine for the treatment of dry eye syndrome.

OBJECTIVE: To assess the comparative effectiveness and cost-effectiveness (cost-utility) of a 0.05% emulsion of topical cyclosporine (Restasis; Allergan Inc, Irvine, California) for the treatment of moderate to severe dry eye syndrome that is unresponsive to conventional therapy. METHODS: Data from 2 multicenter, randomized, clinical trials and Food and Drug Administration files for topical cyclosporine, 0.05%, emulsion were used in Center for Value-Based Medicine analyses. Analyses included value-based medicine as a comparative effectiveness analysis and average cost-utility analysis using societal and third-party insurer cost perspectives. MAIN OUTCOME MEASURES: Outcome measures of comparative effectiveness were quality-adjusted life-year (QALY) gain and percentage of improvement in quality of life, and for cost-effectiveness were cost-utility ratio (CUR) using dollars per QALY. RESULTS: Topical cyclosporine, 0.05%, confers a value gain (comparative effectiveness) of 0.0319 QALY per year compared with topical lubricant therapy, a 4.3% improvement in quality of life for the average patient with moderate to severe dry eye syndrome that is unresponsive to conventional lubricant therapy. The societal perspective incremental CUR for cyclosporine over vehicle therapy is $34,953 per QALY and the societal perspective average CUR is $11,199 per QALY. The third-party-insurer incremental CUR is $37,179 per QALY, while the third-party-insurer perspective average CUR is $34,343 per QALY. CONCLUSIONS: Topical cyclosporine emulsion, 0.05%, confers considerable patient value and is a cost-effective therapy for moderate to severe dry eye syndrome that is unresponsive to conventional therapy.

The goal of value-based medicine analyses: comparability. The case for neovascular macular degeneration.

PURPOSE: To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). METHODS: A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. RESULTS: Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin confers a 7.8% to 10.7% value gain for the treatment of classic subfoveal choroidal neovascularization. Intravitreal ranibizumab therapy confers greater than a 15% value gain for the treatment of subfoveal occult and minimally classic subfoveal choroidal neovascularization. CONCLUSIONS: The majority of cost-utility studies performed on interventions for neovascular macular degeneration are value-based medicine studies and thus are comparable. Value-based analyses of neovascular ARMD monotherapies demonstrate the power of value-based medicine to improve quality of care and concurrently maximize the efficacy of healthcare resource use in public policy. The comparability of value-based medicine cost-utility analyses has important implications for overall practice standards and public policy. The adoption of value-based medicine standards can greatly facilitate the goal of higher-quality care and maximize the best use of healthcare funds.

Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women.

Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-alpha in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-alpha concentrations were relatively low and were weakly associated with malaria. TNF-alpha concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-alpha levels were higher in women who had LBW babies (P = 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in other women. The presence of TNF-alpha in cord blood was not associated with malaria infection. IFN-gamma levels were infrequently elevated, and elevated IFN-gamma levels were not associated with poor pregnancy outcomes. Placental production of TNF-alpha, but not of IFN-gamma, may be implicated in impaired fetal growth in Malawian women.