Health and economic benefits of early vaccination and nonpharmaceutical interventions for a human influenza A (H7N9) pandemic: a modeling study.

BACKGROUND: Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness. OBJECTIVE: To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1). DESIGN: Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city. DATA SOURCES: Literature and expert opinion. TARGET POPULATION: Residents of a U.S. metropolitan city with characteristics similar to New York City. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Vaccination of 30% of the population at 4 or 6 months. OUTCOME MEASURES: Infections and deaths averted and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million. RESULTS OF SENSITIVITY ANALYSIS: If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months. LIMITATION: The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions. CONCLUSION: Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing non-pharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality, National Institutes of Health, and Department of Veterans Affairs.

Cost-effectiveness of genotype-guided and dual antiplatelet therapies in acute coronary syndrome.

BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available. OBJECTIVE: To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS. DESIGN: Decision-analytic model. DATA SOURCES: Published literature, Medicare claims, and life tables. TARGET POPULATION: Patients having percutaneous coronary intervention for ACS. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel. OUTCOME MEASURES: Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor). RESULTS OF SENSITIVITY ANALYSIS: Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor. LIMITATION: No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor. CONCLUSION: Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Cost-effectiveness of early colectomy with ileal pouch-anal anastamosis versus standard medical therapy in severe ulcerative colitis.

BACKGROUND: Inflammatory bowel diseases are costly chronic gastrointestinal diseases. We aimed to determine whether immediate colectomy with ileal pouch-anal anastamosis (IPAA) after diagnosis of severe ulcerative colitis (UC) was cost-effective compared to the standard medical therapy. METHODS: We created a Markov model simulating 2 cohorts of 21-year-old patients with severe UC, following them until 100 years of age or death, comparing early colectomy with IPAA strategy to the standard medical therapy strategy. Deterministic and probabilistic analyses were performed. RESULTS: Standard medical care accrued a discounted lifetime cost of $236,370 per patient. In contrast, early colectomy with IPAA accrued a discounted lifetime cost of $147,763 per patient. Lifetime quality-adjusted life-years gained (QALY-gained) for standard medical therapy was 20.78, while QALY-gained for early colectomy with IPAA was 20.72. The resulting incremental cost-effectiveness ratio (Δcosts/ΔQALY) was approximately $1.5 million per QALY-gained. Results were robust to one-way sensitivity analyses for all variables in the model. Quality-of-life after colectomy with IPAA was the most sensitive variable impacting cost-effectiveness. A low utility value of less than 0.7 after colectomy with IPAA was necessary for the colectomy with IPAA strategy to be cost-ineffective. CONCLUSIONS: Under the appropriate clinical settings, early colectomy with IPAA after diagnosis of severe UC reduces health care expenditures and provides comparable quality of life compared to exhaustive standard medical therapy.

Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation.

BACKGROUND: Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin. OBJECTIVE: To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF. DESIGN: Markov decision model. DATA SOURCES: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom. TARGET POPULATION: Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS2 score ≥1 or equivalent) and no contraindications to anticoagulation. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose). OUTCOME MEASURES: Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran. RESULTS OF SENSITIVITY ANALYSIS: The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage. LIMITATION: Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up. CONCLUSION: In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS2 score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States. PRIMARY FUNDING SOURCE: American Heart Association and Veterans Affairs Health Services Research & Development Service.

Cost-effectiveness analysis of nephron sparing options for the management of small renal masses.

PURPOSE: A recent increase in the detection of contrast enhancing renal masses 4 cm or smaller suspicious for malignancy has led to the widespread use of nephron sparing options. Limited data exist to help clinicians decide which of these competing nephron sparing therapies is most appropriate. We performed a cost-effectiveness analysis to evaluate the relative clinical and economic merits of commonly available nephron sparing strategies for small renal masses. MATERIALS AND METHODS: We developed a decision analytic Markov model estimating the costs and health outcomes of treating a healthy 65-year-old patient with an asymptomatic unilateral small renal mass using competing nephron sparing options of immediate intervention (ie open and laparoscopic partial nephrectomy as well as laparoscopic and percutaneous ablation), active surveillance with possible delayed intervention and nonsurgical management with observation. Benefits were measured in quality adjusted life-years. We used a societal perspective, lifetime horizon and willingness to pay threshold of $50,000 per quality adjusted life-year gained. Model results were assessed with sensitivity analyses. RESULTS: In the base case scenario the least costly option was observation and the optimal option was immediate laparoscopic partial nephrectomy, which had an incremental cost-effectiveness ratio of $36,645 per quality adjusted life-year gained compared to surveillance with possible delayed percutaneous ablation. Results were sensitive to age at diagnosis, health status and tumor size. CONCLUSIONS: Immediate laparoscopic partial nephrectomy is the preferred nephron sparing option for healthy patients younger than 74 years old with a small renal mass. Surveillance with possible delayed percutaneous ablation is a cost-effective alternative for patients with advanced age or significant comorbidities. Observation maximizes quality adjusted life-years in patients who are poor surgical candidates or with limited life expectancy (less than 3 years).

Population strategies to decrease sodium intake and the burden of cardiovascular disease: a cost-effectiveness analysis.

BACKGROUND: Sodium consumption raises blood pressure, increasing the risk for heart attack and stroke. Several countries, including the United States, are considering strategies to decrease population sodium intake. OBJECTIVE: To assess the cost-effectiveness of 2 population strategies to reduce sodium intake: government collaboration with food manufacturers to voluntarily cut sodium in processed foods, modeled on the United Kingdom experience, and a sodium tax. DESIGN: A Markov model was constructed with 4 health states: well, acute myocardial infarction (MI), acute stroke, and history of MI or stroke. DATA SOURCES: Medical Panel Expenditure Survey (2006), Framingham Heart Study (1980 to 2003), Dietary Approaches to Stop Hypertension trial, and other published data. TARGET POPULATION: U.S. adults aged 40 to 85 years. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. OUTCOME MEASURES: Incremental costs (2008 U.S. dollars), quality-adjusted life-years (QALYs), and MIs and strokes averted. RESULTS OF BASE-CASE ANALYSIS: Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513 885 strokes and 480 358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving $32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves $22.4 billion over the same period. RESULTS OF SENSITIVITY ANALYSIS: Results are sensitive to the assumption that consumers have no disutility with modest reductions in sodium intake. LIMITATION: Efforts to reduce population sodium intake could result in other dietary changes that are difficult to predict. CONCLUSION: Strategies to reduce sodium intake on a population level in the United States are likely to substantially reduce stroke and MI incidence, which would save billions of dollars in medical expenses. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Stanford University, and National Science Foundation.

Health outcomes and costs of community mitigation strategies for an influenza pandemic in the United States.

BACKGROUND: The optimal community-level approach to control pandemic influenza is unknown. METHODS: We estimated the health outcomes and costs of combinations of 4 social distancing strategies and 2 antiviral medication strategies to mitigate an influenza pandemic for a demographically typical US community. We used a social network, agent-based model to estimate strategy effectiveness and an economic model to estimate health resource use and costs. We used data from the literature to estimate clinical outcomes and health care utilization. RESULTS: At 1% influenza mortality, moderate infectivity (R(o) of 2.1 or greater), and 60% population compliance, the preferred strategy is adult and child social distancing, school closure, and antiviral treatment and prophylaxis. This strategy reduces the prevalence of cases in the population from 35% to 10%, averts 2480 cases per 10,000 population, costs $2700 per case averted, and costs $31,300 per quality-adjusted life-year gained, compared with the same strategy without school closure. The addition of school closure to adult and child social distancing and antiviral treatment and prophylaxis, if available, is not cost-effective for viral strains with low infectivity (R(o) of 1.6 and below) and low case fatality rates (below 1%). High population compliance lowers costs to society substantially when the pandemic strain is severe (R(o) of 2.1 or greater). CONCLUSIONS: Multilayered mitigation strategies that include adult and child social distancing, use of antivirals, and school closure are cost-effective for a moderate to severe pandemic. Choice of strategy should be driven by the severity of the pandemic, as defined by the case fatality rate and infectivity.

Cost effectiveness of alternative imaging strategies for the diagnosis of small-bowel Crohn's disease.

BACKGROUND & AIMS: The cost effectiveness of alternative approaches to the diagnosis of small-bowel Crohn's disease is unknown. This study evaluates whether computed tomographic enterography (CTE) is a cost-effective alternative to small-bowel follow-through (SBFT) and whether capsule endoscopy is a cost-effective third test in patients in whom a high suspicion of disease remains after 2 previous negative tests. METHODS: A decision-analytic model was developed to compare the lifetime costs and benefits of each diagnostic strategy. Patients were considered with low (20%) and high (75%) pretest probability of small-bowel Crohn's disease. Effectiveness was measured in quality-adjusted life-years (QALYs) gained. Parameter assumptions were tested with sensitivity analyses. RESULTS: With a moderate to high pretest probability of small-bowel Crohn's disease, and a higher likelihood of isolated jejunal disease, follow-up evaluation with CTE has an incremental cost-effectiveness ratio of less than $54,000/QALY-gained compared with SBFT. The addition of capsule endoscopy after ileocolonoscopy and negative CTE or SBFT costs greater than $500,000 per QALY-gained in all scenarios. Results were not sensitive to costs of tests or complications but were sensitive to test accuracies. CONCLUSIONS: The cost effectiveness of strategies depends critically on the pretest probability of Crohn's disease and if the terminal ileum is examined at ileocolonoscopy. CTE is a cost-effective alternative to SBFT in patients with moderate to high suspicion of small-bowel Crohn's disease. The addition of capsule endoscopy as a third test is not a cost-effective third test, even in patients with high pretest probability of disease.

Incidental extracardiac findings at coronary CT: clinical and economic impact.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of incidental extracardiac findings on coronary CT, to determine the associated downstream resource utilization, and to estimate additional costs per patient related to the associated diagnostic workup. MATERIALS AND METHODS: This retrospective study examined incidental extracardiac findings in 151 consecutive adults (69.5% men and 30.5% women; mean age, 54 years) undergoing coronary CT during a 7-year period. Incidental findings were recorded, and medical records were reviewed for downstream diagnostic examinations for a follow-up period of 1 year (minimum) to 7 years (maximum). Costs of further workup were estimated using 2009 Medicare average reimbursement figures. RESULTS: There were 102 incidental extracardiac findings in 43% (65/151) of patients. Fifty-two percent (53/102) of findings were potentially clinically significant, and 81% (43/53) of these findings were newly discovered. The radiology reports made specific follow-up recommendations for 36% (19/53) of new significant findings. Only 4% (6/151) of patients actually underwent follow-up imaging or intervention for incidental findings. One patient was found to have a malignancy that was subsequently treated. The average direct costs of additional diagnostic workup were $17.42 per patient screened (95% CI, $2.84-$32.00) and $438.39 per patient with imaging follow-up (95% CI, $301.47-$575.31). CONCLUSION: Coronary CT frequently reveals potentially significant incidental extracardiac abnormalities, yet radiologists recommend further evaluation in only one-third of cases. An even smaller fraction of cases receive further workup. The failure to follow-up abnormal incidental findings may result in missed opportunities to detect early disease, but also limits the short-term attributable costs.

Effectiveness and cost-effectiveness of vaccination against pandemic influenza (H1N1) 2009.

BACKGROUND: Decisions on the timing and extent of vaccination against pandemic (H1N1) 2009 virus are complex. OBJECTIVE: To estimate the effectiveness and cost-effectiveness of pandemic influenza (H1N1) vaccination under different scenarios in October or November 2009. DESIGN: Compartmental epidemic model in conjunction with a Markov model of disease progression. DATA SOURCES: Literature and expert opinion. TARGET POPULATION: Residents of a major U.S. metropolitan city with a population of 8.3 million. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Vaccination in mid-October or mid-November 2009. OUTCOME MEASURES: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Assuming each primary infection causes 1.5 secondary infections, vaccinating 40% of the population in October or November would be cost-saving. Vaccination in October would avert 2051 deaths, gain 69 679 QALYs, and save $469 million compared with no vaccination; vaccination in November would avert 1468 deaths, gain 49 422 QALYs, and save $302 million. RESULTS OF SENSITIVITY ANALYSIS: Vaccination is even more cost-saving if longer incubation periods, lower rates of infectiousness, or increased implementation of nonpharmaceutical interventions delay time to the peak of the pandemic. Vaccination saves fewer lives and is less cost-effective if the epidemic peaks earlier than mid-October. LIMITATIONS: The model assumed homogenous mixing of case-patients and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. Additional costs and savings not included in the model would make vaccination more cost-saving. CONCLUSION: Earlier vaccination against pandemic (H1N1) 2009 prevents more deaths and is more cost-saving. Complete population coverage is not necessary to reduce the viral reproductive rate sufficiently to help shorten the pandemic. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and National Institute on Drug Abuse.

Effectiveness and cost-effectiveness of expanded antiviral prophylaxis and adjuvanted vaccination strategies for an influenza A (H5N1) pandemic.

BACKGROUND: The pandemic potential of influenza A (H5N1) virus is a prominent public health concern of the 21st century. OBJECTIVE: To estimate the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies. DESIGN: Compartmental epidemic model in conjunction with a Markov model of disease progression. DATA SOURCES: Literature and expert opinion. TARGET POPULATION: Residents of a U.S. metropolitan city with a population of 8.3 million. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: 3 scenarios: 1) vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), 2) stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and 3) stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). All scenarios assumed standard nonpharmaceutical interventions. OUTCOME MEASURES: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404 030 QALYs at $10 844 per QALY gained relative to the stockpiled strategy. RESULTS OF SENSITIVITY ANALYSIS: Expanded vaccination remained incrementally cost-effective over a wide range of assumptions. LIMITATIONS: The model assumed homogenous mixing of cases and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. We did not model interventions for children or older adults; the model is not designed to target interventions to specific groups. CONCLUSION: Expanded adjuvanted vaccination is an effective and cost-effective mitigation strategy for an influenza A (H5N1) pandemic. Expanded antiviral prophylaxis can help delay the pandemic while additional strategies are implemented. PRIMARY FUNDING SOURCE: National Institutes of Health and Agency for Healthcare Research and Quality.

Toward a 21st-century health care system: recommendations for health care reform.

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.

Systematic review: the effects of growth hormone on athletic performance.

BACKGROUND: Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood. PURPOSE: To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007. STUDY SELECTION: Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age. DATA EXTRACTION: 2 authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone. LIMITATIONS: Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens. CONCLUSION: Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.