Special Article
Cost Effectiveness of Thrombolytic Therapy with Tissue Plasminogen Activator as Compared with Streptokinase for Acute Myocardial Infarction
N Engl J Med 1995; 332:1418-1424May 25, 1995DOI: 10.1056/NEJM199505253322106
- Abstract
Background
Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 11/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective.
Methods
Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment.
Results
One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio — with both future costs and benefits discounted at 5 percent per year — was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study.
Conclusions
The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.
Media in This Article
Figure 1
Probability of Survival among Patients Treated with t-PA.Figure 3
Sensitivity Analysis of the Cost Difference between Treatment with t-PA and Treatment with Streptokinase, Assuming No Cost Differences beyond the First Year after Treatment.Article Activity
- Article
The value of thrombolytic therapy for patients with acute myocardial infarction has been firmly established. To identify the thrombolytic approach that most effectively produces sustained patency of the infarct-related artery and improves survival, the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) investigators compared four different regimens: accelerated tissue plasminogen activator (t-PA), streptokinase with intravenous heparin, streptokinase with subcutaneous heparin, and a combination of t-PA and streptokinase.1 (“Accelerated” refers to the administration of t-PA over a period of 11/2 hours — with two thirds of the dose given in the first 30 minutes — rather than the conventional period of 3 hours.) That study found a statistically significant relative decrease of 15 percent and an absolute decrease of 1 percent in 30-day mortality from all causes for treatment with accelerated t-PA as compared with the pooled streptokinase regimens (the mortality rates for which were not significantly different from one another). Furthermore, t-PA reduced the risk of death in each of the analyzed subgroups.1 Some observers have questioned whether the improved survival rates seen in the GUSTO study are worth the substantial additional cost of t-PA.
We conducted a cost-effectiveness analysis to compare the value of t-PA treatment with that of streptokinase treatment on the basis of the information on mortality and use of resources from the GUSTO study and detailed data on the use of medical resources and the quality of life of a random subgroup of the GUSTO cohort residing in the United States.
Methods
Our analysis comparing accelerated t-PA with streptokinase used data from the GUSTO study: data on 1-year survival for all 41,021 patients enrolled in the study, data on the use of medical resources during the initial hospitalization for all 23,105 U.S. patients, and data on a prospective random sample of 2600 U.S. patients who underwent structured interviews by telephone 30 days, 6 months, and 12 months after enrollment on their use of medical resources and quality of life.1,2 The particular costs and benefits examined in a cost-effectiveness analysis vary with the perspective of the study.3,4 In medical economics, the analysis can be constructed to reflect the viewpoint of society as a whole, payers, health care providers, or patients. In the present study, we used a social perspective to identify relevant costs, although indirect costs (e.g., time lost from work) and nonmedical costs were not included. Effectiveness was measured in terms of additional life expectancy, and the effects of the treatments on the patients' quality of life were examined in a sensitivity analysis.5,6 Both survival and costs were discounted continuously at an annual rate of 5 percent, as is consistent with conventional practice.6,7 Extensive sensitivity analyses were performed. Cost-effectiveness ratios were expressed as the additional lifetime costs required to add one extra year of life with t-PA treatment as compared with streptokinase therapy. Higher cost-effectiveness ratios indicate lower cost effectiveness.
Determining Costs
The costs of initial hospitalization (including charges for any transfers between hospitals) were calculated in two ways: from total cost estimates (variable costs plus fixed costs) from the Duke Transition One cost-accounting system, and from Medicare diagnosis-related-group (DRG) reimbursement rates (Table 1Table 1
Costs Used in the Analysis.). The Transition One system estimates hospital costs using a bottom-up approach that is based on resources consumed and unit prices for those resources.3 Costs of the thrombolytic agents were also calculated in two ways: from the Drug Topics Red Book average of 1993 wholesale prices,8 and from the average costs of the drugs in 16 randomly selected GUSTO hospitals (2 hospitals in each GUSTO geographic region).1 The Red Book average wholesale price of 1.5 million units of streptokinase was $320; the price of 100 mg of t-PA was $2,750. The average cost to the 16 GUSTO hospitals was $270 for 1.5 million units of streptokinase and $2,216 for 100 mg of t-PA. We assumed that pharmacy handling and preparation costs and drug-administration costs would be equivalent for the two regimens. For follow-up hospitalization costs, we used Medicare DRG reimbursement rates for North Carolina (Table 1). Reported hospitalizations and revascularization procedures were verified with the relevant institution. Physicians' fees for both initial and follow-up hospitalizations were drawn from the Medicare fee schedule for North Carolina (Table 1).For the primary analysis, incremental costs included only cumulative hospital and physicians' costs for the first year after treatment. Because there were no empirical data on costs after one year, the primary analysis assumed no cost differences between the treatment groups after one year. All costs were expressed in 1993 dollars.
Estimating Survival
To estimate survival rates after the end of follow-up in the GUSTO study, the primary analysis assumed that the hazard of death after one year did not depend on the thrombolytic agent received (i.e., that the survival curves of the two treatment groups were parallel) and that the patients' pattern of long-term survival was typical of the chronic, stable phase of coronary heart disease. To represent that pattern, we constructed a Cox proportional-hazards model based on the experience of 4379 patients in the Duke Cardiovascular Disease Database9-12 with myocardial infarction between 1971 and 1992 who had either pathologic Q waves on a resting 12-lead electrocardiogram or a marked focal wall-motion abnormality seen on a left ventriculogram and who survived at least one year. This survival model was used to extend the 1-year survival data by an additional 14 years. For the model, we selected covariates that were available in the GUSTO data base, including age, sex, and location of infarction. Because, in the Duke data, approximately 20 percent of patients were alive at the last follow-up, we used a Gompertz function to extrapolate the tail of the survival curve.13
Using this composite modeling approach, we generated lifetime survival curves for both treatment groups and calculated life expectancy as the area under each curve. The increase in life expectancy for the t-PA group was thus represented by the difference between the areas under the two curves. The survival curve for the t-PA group is presented in Figure 1Figure 1
Probability of Survival among Patients Treated with t-PA..Sensitivity Analyses
Extensive sensitivity analyses were performed in order to find threshold values for variables in the model that would result in a cost-effectiveness ratio of more than $50,000 per year of life saved. We varied survival and costs in both the short and the long term for the t-PA group, the costs and adverse health consequences of the increased risk of disabling stroke associated with t-PA, and the utility weights we used to reflect the attitude of patients toward their current state of health.
Utility
Utility (a number from 0 to 100 that summarizes the value patients attach to their current state of health) was measured in structured telephone interviews one year after treatment. Patients were asked, in a series of questions, how much of their current life expectancy — assumed to be 10 years in their present state of health — they would be willing to give up in order to live their remaining years in excellent health.14,15
Subgroup Analysis
We calculated the comparative cost-effectiveness value for treatment with t-PA instead of streptokinase for eight clinical subgroups defined by the patient's age (up to 40 years, 41 to 60 years, 61 to 75 years, or more than 75 years) and the location of the infarction (anterior or inferior). In a linear regression analysis, neither age nor the location of the infarction had an identifiable association with costs in the first year after treatment. Consequently, we used the cost differences from our primary analysis in calculating the cost-effectiveness values for the eight subgroups.
Statistical Analysis
Descriptive data are presented as percentages for discrete variables and as medians with 25th and 75th percentiles for continuous variables (Table 2Table 2
Use of Medical Resources during the Initial Hospitalization and up to One Year after Discharge, According to Treatment.). Intention-to-treat analyses of base-line, six-month, and one-year data were performed with a chi-square test for discrete variables and by the Wilcoxon rank-sum test for continuous variables.Results
Primary Analysis
Costs
Resource consumption within the first year was generally similar in the streptokinase and t-PA groups (Table 2). There was a slightly higher use of pulmonary-artery catheters in the patients who received streptokinase during the initial hospitalization (20 percent, vs. 18 percent in the t-PA group; P = 0.002). There was a trend toward more percutaneous transluminal coronary angioplasty in the t-PA group (3 percent vs. 2 percent, P = 0.03) and more rehospitalization (19 percent vs. 15 percent, P = 0.06) from six months to one year after enrollment (Table 2). At the time of initial hospital discharge, there was no difference between the two treatment groups in the rates of use of any of the major classes of cardiac medications. The estimated cumulative medical costs (hospital costs plus physicians' fees) at one year, exclusive of the cost of the thrombolytic agent, averaged $24,575 for patients treated with streptokinase and $24,990 for patients treated with t-PA. When the Red Book drug costs for the thrombolytic agent were added, the incremental, undiscounted costs for each patient who received t-PA were $2,845. The primary analysis assumed no increased costs for the t-PA group after the first year.
Life Expectancy
Survival at 30 days was 92.7 percent in the streptokinase group and 93.7 percent in the t-PA group (P = 0.001), and 89.9 percent and 91.0 percent, respectively, after one year (P = 0.006). We projected a life expectancy from the time of enrollment in the GUSTO study of 15.27 years for patients treated with streptokinase and 15.41 years for patients treated with t-PA, or an undiscounted increase in life expectancy for the t-PA group of 0.14 year per patient (i.e., 14 additional years of life per 100 patients treated with t-PA).
Cost Effectiveness
With an increased life expectancy in the t-PA group of 0.14 year of life per patient, an increased cost of $2,845 per patient, and a discount rate of 5 percent, the comparative primary cost-effectiveness ratio for the use of t-PA instead of streptokinase was $32,678 per year of life saved. Substituting the average thrombolytic-drug costs to the hospitals in the GUSTO study for the Red Book wholesale prices in our primary analysis yielded a cost-effectiveness value of $27,115 per year of life saved. If we used Medicare DRG reimbursement rates for the initial hospitalization rather than the Duke Transition One costs, kept the Red Book prices for the thrombolytic agents, and left all other factors unchanged, the increase in costs for patients treated with t-PA was $3,154 and the cost-effectiveness ratio became $36,218 per year of life saved. Substituting the GUSTO prices for thrombolytic agents into this latter calculation reduced the additional cost of t-PA treatment to $2,670 and lowered the cost-effectiveness value to $30,655 per year of life saved.
Sensitivity Analyses
Differences in One-Year Survival
The 95 percent confidence interval for the 1.1 percent increase in one-year survival among patients in the t-PA group was 0.46 percent to 1.74 percent, a range that would produce cost-effectiveness ratios of $71,039 to $18,781 per year of life saved.
Differences in Long-Term Survival
The true life expectancy of the subjects could differ from the value predicted in our model of approximately 15 years. In addition, the survival curves may actually converge or diverge after one year. Either reducing the life expectancy or causing the survival curves to converge would reduce the additional years of life saved by t-PA treatment (Figure 2Figure 2
Sensitivity Analysis of the Long-Term Increase in Survival in the t-PA Group as Compared with the Streptokinase Group.). With a 5 percent discount rate, the cost-effectiveness ratio would rise above $50,000 if the number of years of life saved by t-PA treatment fell below 7 undiscounted years per 100 patients, and it would rise above $100,000 per year of life saved if the number of undiscounted years of life saved per 100 patients fell below 3.Discounting the value of future costs and benefits reduces their present value. If costs and increased years of life were not discounted at all, the primary cost-effectiveness ratio in our study would be $20,468 per year of life saved; if a discount rate of 10 percent was used, however, the cost-effectiveness ratio would rise to $47,337 per year of life saved.
Cost Differences in the First Year
Although the difference in associated costs between streptokinase and t-PA (exclusive of the cost of the drugs themselves) was not statistically significant, variations in the increased costs associated with t-PA treatment did affect the cost-effectiveness ratio (Figure 3Figure 3
Sensitivity Analysis of the Cost Difference between Treatment with t-PA and Treatment with Streptokinase, Assuming No Cost Differences beyond the First Year after Treatment.). A cost-effectiveness value of $50,000 is reached when the additional cost of t-PA treatment, including the cost of the thrombolytic agents, exceeds $4,350 per patient (53 percent higher than the cost calculated in the primary analysis). If the additional cost of t-PA use were $2,000, the cost-effectiveness ratio would be $27,736 per year of life saved. If the drug costs were those typical in Europe (approximately $1,000 for 100 mg of t-PA and $200 for 1.5 million units of streptokinase), the cost-effectiveness ratio would be $13,943 per year of life saved.Cost Differences after One Year
In the primary analysis, we assumed no cost difference between t-PA and streptokinase beyond the first year after treatment. In a random subgroup of U.S. patients, we observed a mean increased cost per patient for the t-PA group between six months and one year of $508 (P = 0.38). Although it was not statistically significant, we used this figure to estimate the possible increase in long-term costs for subjects who survived one year after treatment. If we annualize this figure to $1,016 per year, discount future costs at 5 percent per year, and calculate on the basis of the average GUSTO patient's life expectancy (15 years), an additional $9,975 is added to the costs associated with t-PA, yielding an incremental cost-effectiveness ratio of $147,333 per year of life saved. If the increased level of cost continues for only the second year after treatment, then the cost-effectiveness ratio would be approximately $44,000. If the higher costs continue through the third year of follow-up, the cost-effectiveness ratio would be approximately $55,300 per year of life saved.
Quality of Life
At one year, the mean utility weights measured in our interviews were 0.90 for both treatment groups. That is, patients were hypothetically willing to trade 10 years of life at their present state of health for 9 years of excellent health. Weighting increased survival in both groups by this factor yielded a cost-effectiveness ratio of $36,402 per quality-adjusted year of life saved.
Increased Risk of Stroke
In the first 30 days after treatment in the GUSTO study, t-PA produced a net increase of one disabling nonfatal stroke per 1000 patients treated, as compared with the rate with streptokinase.1 If disabling nonfatal stroke is considered an end point equivalent to death in the hospital, then the increase in life expectancy estimated for the t-PA group in our model is reduced to 0.13 undiscounted year per patient, and the primary cost-effectiveness ratio increases to $35,538.
Costs for the care of survivors of stroke in the first year after treatment were included in our primary analysis. In a sensitivity analysis, we assumed that patients with stroke who were in a rehabilitation hospital or nursing home one year after treatment (12 percent of the stroke survivors) would incur the costs of such care (an average daily cost of $1,212 for care in a rehabilitation hospital and $155 for nursing home care) for the remainder of their life expectancy. Allocating these extra costs to the t-PA group on the basis of one additional disabling nonfatal stroke per 1000 patients, and counting disabling stroke as an end point equivalent to death in the hospital, produce a cost-effectiveness ratio of $36,238. If each additional disabling stroke in the t-PA group required nursing home care for an average of 15 years, then the cost-effectiveness ratio would be $42,400.
Subgroup Analyses
We calculated incremental cost-effectiveness ratios for eight clinical subgroups defined by age and location of the infarction (Table 3Table 3
Cost-Effectiveness Ratios for t-PA as Compared with Streptokinase in the Primary Analysis and for Selected Subgroups of Patients.). The number of years of life added by treatment with t-PA was greater for older patients than for younger patients and greater for anterior than for inferior infarction. For patients with anterior myocardial infarction, cost-effectiveness ratios were above $50,000 only for subjects 40 years of age or younger. For patients with inferior myocardial infarction, values were above $50,000 for subjects up to 60 years of age.Discussion
The substitution of accelerated t-PA for streptokinase in the treatment of acute myocardial infarction yields increased health benefits at a cost comparable to those of other expensive therapies routinely considered worthwhile. Benchmarks against which the average comparative cost-effectiveness ratio of t-PA ($32,678 per year of life saved) can be measured include that of coronary bypass surgery as compared with medical therapy for left main coronary artery disease ($7,000 per year of life saved), that of medical therapy as compared with no therapy for severe hypertension ($20,000 per year of life saved), and that of hemodialysis as compared with no dialysis for chronic renal failure ($35,000 per year of life saved).16 The upper limit for an acceptable cost-effectiveness ratio remains controversial, but values of more than $100,000 per year of life saved are generally considered too high. Most previous economic analyses of thrombolytic therapy have compared therapy with no therapy rather than comparing different agents.16-18 Several earlier attempts to examine the incremental cost effectiveness of t-PA relative to streptokinase have made assumptions that are inappropriate in the light of the findings of the GUSTO study.1,19,20 However, Naylor et al. found that treatment with t-PA was cost effective, providing that the drug's beneficial effect on survival, as compared with streptokinase, was sustained for five years.21
Sensitivity Analyses
Our sensitivity analysis examined the effects of altering the key assumptions of the cost-effectiveness analysis, such as our estimate of 14 years of life saved per 100 patients treated with t-PA. This estimate was based on our survival model, on the increase in one-year survival observed in patients treated with t-PA as compared with those treated with streptokinase, and on an assumption that the survival curves for the two treatment groups would remain parallel after one year. The assumption that the survival curves will remain parallel is supported by the findings of other studies indicating that the benefit of thrombolysis is sustained through five years of follow-up.22-25 In our sensitivity analysis of the assumed increase in survival, a threshold cost-effectiveness ratio of $50,000 per year of life saved was not exceeded until the increased survival for the t-PA group fell below 7 years of life added per 100 patients treated; a threshold value of $100,000 per year of life saved was not reached until the added years of life per 100 patients treated fell below 3.
Our results were not sensitive to changes in our estimates of costs. Only when the assumed increase in costs attributable to treatment with t-PA during the first year was 1.5 times greater than the value used in our study did the resulting cost-effectiveness ratio exceed $50,000 per year of life saved. If the patients who received t-PA were assumed to have continuing additional costs of about $1,100 per year (a figure projected from the nonsignificant cost difference observed in the second six months of follow-up) past the second follow-up year, the cost-effectiveness ratio became greater than $50,000. However, there is no basis in the empirical data from the GUSTO study for expecting such long-term cost differences between the two treatments.
Importance of Disabling Strokes
One important question is the extent to which the additional hemorrhagic strokes produced by t-PA may cancel out some of the observed increase in survival, thereby making t-PA less attractive and less cost effective.1 However, even the most unfavorable assumptions about nonfatal disabling stroke — that patients with stroke had no increase in survival due to t-PA and that each patient would require 15 years of institutional care — increased the cost-effectiveness ratio only moderately (to $42,400), because these costs were incurred by only 1 patient per 1000 receiving t-PA.
Subgroup Analyses
As is true of the main GUSTO study, our subgroup analyses should be interpreted cautiously.1 For most of the eight subgroups we studied, defined on the basis of age and location of the infarction, the cost-effectiveness ratio was below our benchmark figure of $50,000 per year of life saved. The cost-effectiveness ratios were least favorable for patients 40 years of age or younger and for patients 60 years of age or younger with inferior-wall infarctions, since these groups had the lowest one-year mortality rates and the smallest increases in survival due to treatment with t-PA.26 In our study, we calculated the life expectancies of treated subgroups on the basis of our survival model, rather than on short-term empirical data for each subgroup. This technique provided more stable and consistent estimates than the alternative approach and also allowed us to control for the fact that anterior myocardial infarction was more frequent in older patients.
Conclusions
The routine substitution of accelerated t-PA for streptokinase in the treatment of the approximately 250,000 eligible patients who have acute myocardial infarction in the United States each year would be cost effective by customary criteria. It would cost the nation approximately $500 million each year but would also provide 3.5 million additional years of life for patients after myocardial infarction. Our analysis can inform the decision about whether this should become the standard of care in the United States, but society itself must make the choice.
Supported in part by grants from the Agency for Health Care Policy and Research (HS-05635 and HS-06503), Genentech, the National Heart, Lung, and Blood Institute (HL-36587 and HL-17670), and the Robert Wood Johnson Foundation.
We are indebted to the international GUSTO investigators at 1081 hospitals in 15 countries, without whose hard work and commitment the present study would not have been possible; to Dr. Stephen Pauker for his editorial assistance; to Julia Burchett and Celia Hybels for data-collection support; to Linda Davidson-Ray for assistance in developing the cost data; to the GUSTO Steering Committee for their review of the manuscript and their useful suggestions; and to Maria Lee and Serena Smith for assistance in the preparation of the manuscript.
Source Information
From the Economic and Quality of Life Coordinating Center (D.B.M., C.L.N., N.C.-C., J.D.K.) and the Clinical Trials Coordinating Center (R.M.C., K.L.L.), Division of Cardiology, Department of Medicine, and the Division of Biometry, Department of Community and Family Medicine (K.L.L., F.E.H.), Duke University Medical Center, Durham, N.C.; the Division of Health Services Research, Department of Health Research and Policy, Stanford University School of Medicine, Palo Alto, Calif. (M.A.H.); the Department of Medicine, University of Toronto, and the Institute for Clinical Evaluative Sciences, Toronto (C.D.N.); the Department of Medicine, University of Alberta, Edmonton (P.W.A.); Tel Aviv Sorasky University Medical Center, Tel Aviv, Israel (G.B.); the Cardiology Department, Green Lane Hospital, Auckland, New Zealand (H.W.); Erasmus University, Rotterdam, the Netherlands (M.L.S.); the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia (J.S.); and the Department of Cardiology, Cleveland Clinic, Cleveland (E.J.T.).
Address reprint requests to Dr. Mark at P.O. Box 3485, Duke University Medical Center, Durham, NC 27710.
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S. Ali, S. Ronaldson. (2012) Ordinal preference elicitation methods in health economics and health services research: using discrete choice experiments and ranking methods. British Medical Bulletin 103:1, 21-44
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S G Pauker, F R Goss. (2012) Using Models to Predict the Future: What to Do When the Data Run Out?. Clinical Pharmacology & Therapeutics 91:5, 769-771
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Daniel Mark. Medical Economics in Interventional Cardiology. In: Textbook of Interventional Cardiology. Elsevier, 2012:861-876.
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C. Lucioni, S. Mazzi, M. Gozzo, C. Lazzeri. (2011) Valutazione economica di ticagrelor vs Clopidogrel nel trattamento di pazienti con sindrome coronarica acuta. PharmacoEconomics Italian Research Articles 13:2, 53-64
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Neil Hawkins, David A. Scott. (2011) Reimbursement and value-based pricing: stratified cost-effectiveness analysis may not be the last word. Health Economics 20:6, 688-698
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Nathalie Eckard, Magnus Janzon, Lars-Åke Levin. (2011) Compilation of cost-effectiveness evidence for different heart conditions and treatment strategies. Scandinavian Cardiovascular Journal1-16
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Nicholas Young, Stephen Kinsella, Christopher C. Raio, Matthew Nelson, Gerardo Chiricolo, Ashley Johnson, George Malcolm, Byron C. Drumheller, Mary Frances Ward, Andrew Sama. (2010) Economic Impact of Additional Radiographic Studies After Registered Diagnostic Medical Sonographer (RDMS)-Certified Emergency Physician-Performed Identification of Cholecystitis by Ultrasound. The Journal of Emergency Medicine 38:5, 645-651
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Joseph Heyse, John R. Cook, Michael F. Drummond. Pharmacoeconomics. In: Encyclopedia of Biopharmaceutical Statistics. Informa Healthcare, 2010:999-1010.
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S.J. Thurston, B. Heeg, F. de Charro, B. van Hout. (2010) Cost-effectiveness of clopidogrel in STEMI patients in the Netherlands: a model based on the CLARITY trial. Current Medical Research and Opinion 26:3, 641-651
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Andrea Messori, Sabrina Trippoli, Massimo Bonacchi, Guido Sani. (2009) Left ventricular assist device as destination therapy: Application of the payment-by-results approach for the device reimbursement. The Journal of Thoracic and Cardiovascular Surgery 138:2, 480-485
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Roberto R. Giraldez, Stephen D. Wiviott, Jose C. Nicolau, Satishkumar Mohanavelu, David A. Morrow, Elliott M. Antman, Robert P. Giugliano. (2009) Streptokinase and Enoxaparin as an Alternative to Fibrin-Specific Lytic-Based Regimens. Drugs 69:11, 1433-1443
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Peter J. Neumann. (2009) Costing and Perspective in Published Cost-Effectiveness Analysis. Medical Care 47:Supplement, S28-S32
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Nicolas Penel, Yazdan Yazdanpanah. (2009) Vancomycin flush as antibiotic prophylaxis for early catheter-related infections: a cost-effectiveness analysis. Supportive Care in Cancer 17:3, 285-293
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Jenny F. Homer, Michael F. Drummond, Michael T. French. (2008) Economic Evaluation of Adolescent Addiction Programs: Methodologic Challenges and Recommendations. Journal of Adolescent Health 43:6, 529-539
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Jonathan M. Tan, Alex Macario. (2008) How to Evaluate Whether a New Technology in the Operating Room is Cost-Effective from Society's Viewpoint. Anesthesiology Clinics 26:4, 745-764
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Scott D Grosse. (2008) Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Review of Pharmacoeconomics & Outcomes Research 8:2, 165-178
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Mark Sculpher. (2008) Subgroups and Heterogeneity in Cost-Effectiveness Analysis. PharmacoEconomics 26:9, 799-806
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Duncan Mortimer. (2008) Modelling Downstream Effects in the Presence of Technological Change. PharmacoEconomics 26:12, 991-1003
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H. Melliez, D. Levybruhl, P.Y. Boelle, B. Dervaux, S. Baron, Y. Yazdanpanah. (2008) Cost and cost-effectiveness of childhood vaccination against rotavirus in France. Vaccine 26:5, 706-715
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C Orsi, B Bartolozzi, A Messori, A Bosi. (2007) Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplantation 40:7, 643-649
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Farooq A. Chaudhry, Ehtasham A. Qureshi, Siu-Sun Yao, Sripal Bangalore. (2007) Risk Stratification and Prognosis in Octogenarians Undergoing Stress Echocardiographic Study. Echocardiography 24:8, 851-859
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Wei-Shi Yeh, Edward P Armstrong, Grant H Skrepnek, Daniel C Malone. (2007) Peginterferon alfa-2a versus Peginterferon alfa-2b as Initial Treatment of Hepatitis C Virus Infection: A Cost-Utility Analysis from the Perspective of the Veterans Affairs Health Care System. Pharmacotherapy 27:6, 813-824
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Yan Gong, Amber L. Beitelshees, Jennifer Wessel, Taimour Y. Langaee, Nicholas J. Schork, Julie A. Johnson. (2007) Single nucleotide polymorphism discovery and haplotype analysis of Ca2+-dependent K+ channel beta-1 subunit. Pharmacogenetics and Genomics 17:4, 267-275
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Luciana Ogioni, Rosa Liperoti, Francesco Landi, Manuel Soldato, Roberto Bernabei, Graziano Onder. (2007) Cross-Sectional Association Between Behavioral Symptoms and Potential Elder Abuse Among Subjects in Home Care in Italy: Results From the Silvernet Study. American Journal of Geriatric Psychiatry 15:1, 70-78
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Mark J. Sculpher, Karl Claxton, Mike Drummond, Chris McCabe. (2006) Whither trial-based economic evaluation for health care decision making?. Health Economics 15:7, 677-687
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Thomas D. Szucs, Majbrit V. Holm, Matthias Schwenkglenks, Zefeng Zhang, William S. Weintraub, Michel Burnier, Paul Erne. (2006) Cost-Effectiveness of Eplerenone in Patients with Left Ventricular Dysfunction after Myocardial Infarction—An Analysis of the EPHESUS Study from a Swiss Perspective. Cardiovascular Drugs and Therapy 20:3, 193-204
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Bryan R. Luce, Josephine Mauskopf, Frank A. Sloan, Jan Ostermann, L. Clark Paramore. (2006) The Return on Investment in Health Care: From 1980 to 2000. Value in Health 9:3, 146-156
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Arthur M. Feldman, Gregory de Lissovoy, Michael R. Bristow, Leslie A. Saxon, Teresa De Marco, David A. Kass, John Boehmer, Steven Singh, David J. Whellan, Peter Carson, Audra Boscoe, Timothy M. Baker, Matthew R. Gunderman. (2005) Cost Effectiveness of Cardiac Resynchronization Therapy in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial. Journal of the American College of Cardiology 46:12, 2311-2321
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Gabriel Chodick, Shai Ashkenazi, Gilat Livni, Yehuda Lerman. (2005) Cost-effectiveness of varicella vaccination of healthcare workers. Vaccine 23:43, 5064-5072
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Michael F. Drummond. (2005) Economic Evaluation of Treatment Strategies in Gastroenterology. The American Journal of Gastroenterology 100:10, 2143-2145
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Krista F. Huybrechts, J. Jaime Caro, David A. Wilson, Judith A. O'Brien. (2005) Health and Economic Consequences of Sevelamer Use for Hyperphosphatemia in Patients on Hemodialysis. Value in Health 8:5, 549-561
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Jeffrey S. Brown, George Papadopoulos, Peter J. Neumann, Mark Friedman, Jeffrey D. Miller, Joseph Menzin. (2005) Cost-Effectiveness of Topiramate in Migraine Prevention: Results From a Pharmacoeconomic Model of Topiramate Treatment. Headache: The Journal of Head and Face Pain 45:8, 1012-1022
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Shelby D. Reed, Jasmina I. Radeva, Kevin P. Weinfurt, John J.V. McMurray, Marc A. Pfeffer, Eric J. Velazquez, Jennifer S. Allsbrook, Leah E. Masselink, Mary Ann Sellers, Robert M. Califf, Kevin A. Schulman. (2005) Resource use, costs, and quality of life among patients in the multinational Valsartan in Acute Myocardial Infarction Trial (VALIANT). American Heart Journal 150:2, 323-329
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Michael Drummond, Mark Sculpher. (2005) Common Methodological Flaws in Economic Evaluations. Medical Care 43:Supplement, II-5-II-14
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Markus Sagmeister, Beat Müllhaupt. (2005) Is living donor liver transplantation cost-effective?. Journal of Hepatology 43:1, 27-32
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Şule Apikoğlu Rabuş, Fikret Vehbi lzzettin, Mesut Sancar, Murat Bülent Rabuş, Cevat Kırma, Cevat Yakut. (2005) Cost-Effectiveness of Thrombolytics: A Simplified Model. Pharmacy World & Science 27:3, 243-248
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Padma Kaul, Paul W. Armstrong, Patricia A. Cowper, Eric L. Eisenstein, Christopher B. Granger, Frans Van de Werf, Daniel B. Mark. (2005) Economic analysis of the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-3) study: Costs of reperfusion strategies in acute myocardial infarction. American Heart Journal 149:4, 637-644
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Shelby D. Reed, Kevin J. Anstrom, Ameet Bakhai, Andrew H. Briggs, Robert M. Califf, David J. Cohen, Michael F. Drummond, Henry A. Glick, Ari Gnanasakthy, Mark A. Hlatky, Bernie J. O'Brien, Frank M. Torti, Anastasios A. Tsiatis, Andrew R. Willan, Daniel B. Mark, Kevin A. Schulman. (2005) Conducting economic evaluations alongside multinational clinical trials: Toward a research consensus. American Heart Journal 149:3, 434-443
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J Ruof, A Golay, C Berne, C Collin, J Lentz, A Maetzel. (2005) Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland. International Journal of Obesity
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Michael B. Rothberg, David N. Rose. (2005) Vaccination versus treatment of influenza in working adults: A cost-effectiveness analysis. The American Journal of Medicine 118:1, 68-77
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Shelby D. Reed, Kevin J. Anstrom, Jennifer A. Ludmer, G. Alastair Glendenning, Kevin A. Schulman. (2004) Cost-effectiveness of imatinib versus interferon-? plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer 101:11, 2574-2583
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David J. Cohen, Sabina A. Murphy, Donald S. Baim, Tara A. Lavelle, Ronna H. Berezin, Donald E. Cutlip, Kalon K.L. Ho, Richard E. Kuntz. (2004) Cost-effectiveness of distal embolic protection for patients undergoing percutaneous intervention of saphenous vein bypass grafts. Journal of the American College of Cardiology 44:9, 1801-1808
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Eric Eisenstein, Daniel Mark. Cost-Effectiveness of New Diagnostic Tools and Therapies for Acute Coronary Syndromes. In: Acute Coronary Syndromes, Third Edition. CRC Press, 2004:723-745.
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David F Kong, Eric L Eisenstein, Michael H Sketch, James P Zidar, Thomas J Ryan, Robert A Harrington, Mark F Newman, Peter K Smith, Daniel B Mark, Robert M Califf. (2004) Economic impact of drug-eluting stents on hospital systems: a disease-state model. American Heart Journal 147:3, 449-456
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D. R. Globe, R. G. Curtis, M. A. Koerper, . (2004) Utilization of care in haemophilia: a resource-based method for cost analysis from the Haemophilia Utilization Group Study (HUGS). Haemophilia 10:s1, 63-70
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Sixten Borg, Åsa Ericsson, Jadwiga Wedzicha, Amund Gulsvik, Bo Lundbäck, Gavin C. Donaldson, Sean D. Sullivan. (2004) A Computer Simulation Model of the Natural History and Economic Impact of Chronic Obstructive Pulmonary Disease. Value in Health 7:2, 153-167
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William Weintraub, Bengt J??nsson, Michel Bertrand. (2004) The Value of Clopidogrel in Addition to Standard Therapy in Reducing Atherothrombotic Events. PharmacoEconomics 22:Supplement 4, 29-41
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Andrew F. Shorr, Gregory M. Susla, Marin H. Kollef. (2004) Linezolid for treatment of ventilator-associated pneumonia: A cost-effective alternative to vancomycin*. Critical Care Medicine 32:1, 137-143
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Thomas Hanslik, Pierre-Yves Boëlle, Michael Schwarzinger, Fabrice Carrat, Kenneth A Freedberg, Alain-Jacques Valleron, Antoine Flahault. (2003) Varicella in French adolescents and adults: individual risk assessment and cost-effectiveness of routine vaccination. Vaccine 21:25-26, 3614-3622
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Tim Ibbotson, Jane K McGavin, Karen L Goa. (2003) Abciximab. Drugs 63:11, 1121-1163
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Susana Clemente Bautista, Luís Mendante Barrenechea, José Bruno Montoro Ronsano. (2003) Marco actual de los productos biotecnológicos según los estudios farmacoeconómicos disponibles. Medicina Clínica 120:13, 498-504
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Rochelle P. Walensky, A. David Paltiel, Kenneth A. Freedberg. (2002) AIDS Drug Assistance Programs: Highlighting Inequities in Human Immunodeficiency Virus–Infection Health Care in the United States. Clinical Infectious Diseases 35:5, 606-610
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