Prevalence, referral patterns, testing, and surgery in aortic valve disease: leaving women and elderly patients behind?

BACKGROUND AND AIM OF THE STUDY: The prevalence of aortic valve disease is not well defined, and it is not known to what degree gender and age affect testing and surgery for this condition. The study aim was to describe the prevalence of aortic valve disease in the United States population by extrapolating from administrative claims databases; and to investigate differences associated with gender and age in referral, diagnostic testing, and aortic valve replacement (AVR). METHODS: A claims database of approximately five million privately insured beneficiaries and a 5% sample of Medicare beneficiaries were queried for patients with aortic valve disease. Prevalence was calculated by age group and gender, and extrapolated to the 2005 US population. The proportion of patients with a cardiologist or cardiovascular surgeon visit, performance of echocardiography or stress testing, and AVR within a year of diagnosis was determined. RESULTS: The extrapolated prevalence of aortic valve disease in the US in 2005 was 1.8% (approximately 5.2 million people); in persons aged > or =65 years, prevalence was 10.7%. Women were seen by a specialist, underwent diagnostic tests and underwent AVR at rates significantly lower than men, as did patients aged > or =80 years compared to those aged 65-79 years. AVR was performed at approximately half the rate in women (1.4%) compared to men (2.7%, p <0.001), and in patients aged > or =80 years (1.1%) compared to those aged 65-79 years (2.5%, p <0.001). CONCLUSION: In 2005, approximately 5.2 million adults in the US were estimated to have a diagnosis of aortic valve disease. Advanced age and female gender were associated with lower rates of specialist visits, diagnostic testing, and AVR.

Geographic variation in the prescription of schedule II opioid analgesics among outpatients in the United States.

OBJECTIVE: To measure geographic variation in opioid use in a large, commercially insured, outpatient population in the United States. DATA SOURCES: Outpatient prescription drug claims database of a national pharmaceutical benefit manager for 7,873,337 subjects with at least one prescription drug claim in 2000. STUDY DESIGN: We measured the period prevalence of claims for opioid analgesics and controlled-release oxycodone at the state level. We measured geographic variation using the weighted coefficient of variation and systematic component of variation. In county-level multivariable regression, we explored associations between potential explanatory variables and claims for opioid analgesics and controlled-release oxycodone. PRINCIPAL FINDINGS: A total of 567,778 (64.2 per 1,000 total claims) were for oral opioid analgesics. Claim rates by state ranged from <20 to >100 claims per 1,000 total claims. States with long-standing prescription monitoring programs had among the lowest rates. In the county-level data, presence of a statewide prescription monitoring program and proportions of the population aged 15-24 and 65 years and older were independently and negatively associated with claim rates for all opioid analgesics. Surgeons per 1,000, proportion of the population reporting illicit drug use, and proportion who were female were independently and positively associated with claim rates for all opioid analgesics. Only the proportion of the population aged 25-34 and number of surgeons per 1,000 were independently and positively associated with claim rates for oxycodone. CONCLUSIONS: Claim rates for opioid analgesics vary significantly by state. Presence of a statewide prescription monitoring program is associated with lower claim rates at the county level. Future research should use individual-level data to assess whether these findings reflect a reduction in abuse and diversion or suboptimal treatment of pain.

Economic evaluation of weekly epoetin alfa versus biweekly darbepoetin alfa for chemotherapy-induced anaemia: evidence from a 16-week randomised trial.

INTRODUCTION: A 16-week, open-label, multicentre, randomised trial of weekly epoetin alfa 40 000 units versus biweekly darbepoetin alfa 200microg among 358 patients with solid-tumour cancers and chemotherapy-induced anaemia demonstrated superior haematological outcomes with epoetin alfa. We sought to compare resource use, costs and clinical outcomes between treatment groups and report the results using a cost-consequences framework. METHODS: Pre-specified methods were used to assign costs (US dollars, year 2004-5 values) to medical resources and patient time using a societal perspective. Costs for inpatient care, outpatient care and physician services were based on US Medicare reimbursement rates. Indirect costs assigned to patient time spent receiving study medication were based on the mean hourly wage in the US. In the base-case analysis, the average wholesale price was used to assign costs to medications. Clinical outcomes included all haemoglobin levels and transfusions recorded throughout the trial. Sensitivity analyses were performed to evaluate the impact of different costing methods, cost sources, perspectives and methods to assign haemoglobin values following a blood transfusion. RESULTS: Over a mean follow-up duration of 11.8 weeks, the average cost of study medications and their administration was the single largest component of total costs and was similar between groups (epoetin alfa 5979 US dollars and darbepoetin alfa 5935 US dollars, difference 44 US dollars; 95% CI -590, 692). There were no significant differences in the proportions of patients hospitalised (epoetin alfa 24.6%, darbepoetin alfa 22.0%; p = 0.57). Patients randomised to epoetin alfa experienced more inpatient days, on average, than patients randomised to darbepoetin alfa (2.6 vs 1.6, 95% CI for the difference, 0.07, 2.27). However, with regard to transfusions, patients in the epoetin alfa arm required fewer units of blood than patients in the darbepoetin alfa arm (0.46 vs 0.88, 95% CI for the difference -0.77, -0.08). Mean total costs, comprising costs for study medications and their administration, inpatient care, transfusions, unplanned radiation therapy, haematology and laboratory services, chemotherapy and non-chemotherapy drugs and indirect costs were 14,976 US dollars in the epoetin alfa arm compared with 14,101 US dollars in the darbepoetin alfa arm, a difference of 875 US dollars (95% CI for difference -849, 2607), of which 98% of the difference was attributable to higher inpatient costs in the epoetin alfa arm (2374 US dollars vs 1520 US dollars; 95% CI for difference -33, 1955). Assessments of multiple clinical measures demonstrated improved outcomes with epoetin alfa relative to darbepoetin alfa. CONCLUSION: Most clinical outcome measures suggested greater improvement with epoetin alfa relative to darbepoetin alfa, but most costs for both agents appeared similar. Decision makers must evaluate the differences in costs and efficacy measures that are most relevant from their perspectives.

Early hemoglobin response and alternative metrics of efficacy with erythropoietic agents for chemotherapy-related anemia.

OBJECTIVE: To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia. RESEARCH DESIGN AND METHODS: Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (> or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion. MAIN OUTCOME MEASURES: Efficacy measures included: the proportion of patients with a > or = 1 g/dL increase in hemoglobin by 4 weeks or a > or = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range. RESULTS: A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred. CONCLUSIONS: Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.

Resource use, costs, and quality of life among patients in the multinational Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: In a multinational clinical trial, valsartan was statistically not inferior to captopril in reducing mortality and cardiovascular morbidity after myocardial infarction (MI) in patients with signs of heart failure and/or left ventricular dysfunction. We conducted a prospective economic evaluation to compare within-trial resource use, costs, and quality of life in patients receiving valsartan, captopril, or both after MI. METHODS: We assigned country-specific unit costs to resource use data for 14703 patients and measured health-related quality of life in a subset of 4524 patients. We used the nonparametric bootstrap method to compare rates of resource use and costs, and a piecewise linear mixed-effects regression analysis to compare longitudinal measures of quality of life. RESULTS: There were no significant differences in rates of resource use between the valsartan and captopril groups. During an average follow-up of 2 years, total costs for patients receiving valsartan were significantly higher than for patients receiving captopril (USD 14103 vs USD 13038; 95% CI USD 369-USD 1875). The cost differential was caused primarily by the cost of the study medications (USD 1056 for valsartan vs USD 165 for captopril; 95% CI USD 867 to USD 912). Quality of life did not differ significantly between groups. CONCLUSIONS: For most patients at high risk after MI, the availability of generic captopril confers a cost advantage over valsartan because of lower medication costs. The difference will be smaller or nonexistent in settings where brand-name ACE inhibitors are prescribed.

Economic evaluation of zoledronic acid versus pamidronate for the prevention of skeletal-related events in metastatic breast cancer and multiple myeloma.

Skeletal complications of cancer decrease health-related quality of life. Bisphosphonates can prevent skeletal-related events. We collected resource use data prospectively for 930 patients alongside a multinational trial of zoledronic acid versus pamidronate for patients with metastatic multiple myeloma or breast cancer and > or =1 bone lesion. Country-specific unit costs were assigned to counts of resource use from randomization through last trial visit. Total costs were calculated by summing costs for medical resources, plus costs of institutional care and study medications and administration. Resource use was similar for both groups. Approximately half of the patients were hospitalized at least once during the mean follow-up of 10 months (52.8% for zoledronic acid versus 52.6% for pamidronate; P = 0.9504). The average number of hospital days was 8.9 for zoledronic acid versus 9.2 for pamidronate (P = 0.728). The mean total cost was 16,434 dollars for zoledronic acid and 15,735 dollars for pamidronate, an incremental cost of 699 dollars (95% confidence interval [CI], -1047 to 2163). Mean total costs for patients with multiple myeloma were 1982 dollars (95% CI, -1491 to 5335) higher for zoledronic acid (17,958 dollars) than for pamidronate (15,976 dollars). However, among patients with breast cancer, total costs in both groups were approximately equal (15,703 dollars for zoledronic acid versus 15,680 dollars for pamidronate; 95% CI for the difference: -1875 to 2012). There were no significant cost differences between patients receiving zoledronic acid and those receiving pamidronate.

Economic evaluation of everolimus vs. azathioprine at one year after de novo heart transplantation.

BACKGROUND: Everolimus decreases acute rejection and cardiac allograft vasculopathy after heart transplantation. We compared within-trial costs and resource use over 1 yr of follow-up in de novo heart transplant patients randomized to everolimus 1.5 mg/d (n = 209), everolimus 3.0 mg/d (n = 211), or azathioprine (n = 214). PATIENTS AND METHODS: Resource use data were collected prospectively for 634 patients from 14 countries. We used the nonparametric bootstrap method to test for differences in mean costs and to estimate confidence intervals for cost-effectiveness ratios. RESULTS: Everolimus patients had lower incidence of efficacy failure compared with azathioprine patients (41.6%, everolimus 1.5 mg; 32.2%, everolimus 3.0 mg; 52.8%, azathioprine). Compared with patients receiving azathioprine, everolimus patients spent more days in the hospital [36.3 d for everolimus 1.5 mg/d (p = 0.21); 38.4 d for everolimus 3.0 mg/d (p = 0.01); 32.2 d for azathioprine]. Mean total costs, excluding the study medications, were not significantly different among treatment groups ($72 065 for everolimus 1.5 mg; $72 631 for everolimus 3.0 mg; $70 815 for azathioprine). CONCLUSIONS: Over 1 yr of follow-up after heart transplantation, everolimus did not significantly increase treatment costs, excluding the costs of the study medications, while reducing efficacy failure. Longer follow-up and the cost of everolimus are required to fully evaluate the cost-effectiveness of everolimus vs. azathioprine in post-transplant maintenance.

Cost-effectiveness of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer.

PURPOSE: We estimated the cost-effectiveness of zoledronic acid vs placebo for decreasing skeletal complications in men with prostate cancer. MATERIALS AND METHODS: We performed a cost-effectiveness analysis alongside a multinational clinical trial of zoledronic acid. Cost estimation was based on prospectively collected resource use data for 85.3% of enrolled patients. Cost-effectiveness ratios were based on within-trial data on clinical outcomes, quality of life and study medication cost. RESULTS: Patients receiving zoledronic acid experienced fewer hospital days during a mean followup of 9 months (average 5.6 vs 8.0 days; p = 0.1910). Mean direct costs excluding study medication were US dollars 5365 for patients receiving zoledronic acid and US dollars 5689 for patients receiving placebo, a difference of US dollars 324 (95% CI US dollars 1781 to US dollars 1146). The global average cost of zoledronic acid plus its administration during the trial was US dollars 5677 (US dollars 450 per dose). The nominal cost per skeletal complication avoided was US dollars 112300 (95% CI US dollars 6900 to US dollars 48700) and the cost per additional patient free of skeletal complications was US dollars 51400 (95% CI US dollars 26900 to US dollars 243700). Nominal within-trial cost per quality adjusted life-year was US dollars 159200, which varied widely in sensitivity analyses. CONCLUSIONS: The nominal base case estimate of the cost per quality adjusted life-year for zoledronic acid in the prevention of skeletal complications of prostate cancer is consistent with that of bisphosphonates in breast cancer. However, the cost-effectiveness ratios for bisphosphonates are higher than commonly cited thresholds for conferring cost-effectiveness.