Reducing high blood cholesterol level with drugs. Cost-effectiveness of pharmacologic management

We performed a cost-effectiveness analysis of pharmacologic treatment of high blood cholesterol levels. Agents modeled were cholestyramine, colestipol, gemfibrozil, lovastatin, niacin, and probucol. Pharmacologic effectiveness was estimated from reported studies. Cost estimates reflect societal resource consumption. Annual costs for therapy ranged from $327 (niacin) to $1881 (lovastatin, 80 mg/d). Niacin was the most efficient agent for reducing low-density lipoprotein cholesterol levels, having an average cost over 5 years of $139 per percent reduction in low-density lipoprotein cholesterol level. Lovastatin (20 mg/d) was also efficient ($177 per percent reduction). Cholestyramine was least efficient at $347. For high-density lipoprotein cholesterol, niacin was most efficient, at $116 per percent increase in high-density lipoprotein cholesterol level, followed by gemfibrozil at $271. Analyses combining low-density lipoprotein cholesterol and high-density lipoprotein cholesterol effects suggest that niacin and lovastatin (20 mg/d) were most efficient for reducing cardiovascular risk.     

High fiber diet in hyperlipemia. Comparison with cholestyramine treatment in type IIA hyperlipoproteinemia

Fourteen patients with type IIa hyperlipoproteinemia were treated with a high fiber intake (powdered cellulose or soy hulls or both) for six months. Eight of the patients were treated with 16 g of cholestyramine resin daily without the high fiber intake for an additional six months. The cholesterol intake was comparable in both treatment programs. The mean serum cholesterol levels decreased during both, but the decrease occurred and was more pronounced in all patients treated with cholestyramine. Responsiveness to the high fiber diet was not related to an increased responsiveness to cholestyramine treatment. In most patients the serum triglyceride levels increased, and the fasting plasma glucose level did not change substantially during either treatment program. Both regimens were free of adverse side effects.     

The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. A dose-controlled study

Oat cereals rich in the water-soluble fiber beta-glucan have been studied as a dietary therapy for hypercholesterolemia. To determine the hypocholesterolemic response of beta-glucan in the diet, 156 adults with low-density lipoprotein cholesterol (LDL-C) levels above 4.14 mmol/L (160 mg/dL) or between 3.37 and 4.14 mmol/L (130 and 160 mg/dL) with multiple risk factors were randomized to one of seven groups. Six groups received either oatmeal or oat bran at doses (dry weight) of 28 g (1 oz), 56 g (2 oz), and 84 g (3 oz). A seventh group received 28 g of farina (beta-glucan control). At week 6 of treatment, significant differences were found for both total cholesterol and LDL-C levels among the farina control and the treatment groups who were receiving 84 g of oatmeal, 56 g of oat bran, and 84 g of oat bran, with decreases in LDL-C levels of 10.1%, 15.9%, and 11.5%, respectively. Fifty-six grams of oat bran resulted in significantly greater reductions in LDL-C levels than 56 g of oatmeal. Nutrient analysis shows no difference in dietary fat content between these treatment groups; therefore, the higher beta-glucan content of oat bran most likely explains the significantly greater LDL-C reductions. A dose-dependent reduction in LDL-C levels with oat cereals supports the independent hypocholesterolemic effects of beta-glucan.     

Cost-effectiveness of prescribing statins according to pharmaceutical benefits scheme criteria.

OBJECTIVES: (i) To analyse how well Pharmaceutical Benefits Scheme (PBS) criteria for prescribing lipid-lowering therapy identify people most at risk of coronary heart disease (CHD); and (ii) to determine the cost-effectiveness of primary prevention therapy with pravastatin according to these criteria in Australia. DESIGN: (i) Analysis of targeting of CHD risk according to PBS criteria; (ii) cost-effectiveness analysis for pravastatin as primary preventive therapy (40 mg/day), with a 20-year projection from 1999. PARTICIPANTS: (i) Men and women aged 25-69 years from the 1989 National Heart Foundation Risk Factor Prevalence Survey; (ii) Australian men and women, aged 25-85 years, excluding those with diabetes and existing CHD. MAIN OUTCOME MEASURES: (i) Proportion eligible for lipid lowering treatment according to PBS criteria within 15-year risk of CHD mortality groups; (ii) average net cost in Australian dollars ($) per year of life saved (YOLS), with 80% uncertainty ranges (UR). RESULTS: (i) PBS criteria do not adequately identify those most at risk of CHD, as only 61% of Australians (aged 25-69 years) with a greater than 10% 15-year risk of CHD mortality were eligible for treatment; and 11% of those at low risk of CHD mortality (< 2.5% over 15 years) were eligible for treatment. (ii) Cost-effectiveness of treatment according to PBS criteria was estimated at $110,000 (80% UR, $96,000-$150,000) per YOLS for men and $87,000 (80% UR, $80,000-$130,000) per YOLS for women. As an indicator of the likely recurrent annual costs, total first-year treatment costs (excluding the costs of non-compliers) were estimated at $940 million. Assuming compliance of 50%, cost-effectiveness of treatment was markedly improved using 32.5% 15-year risk of CHD mortality as a cut-off, with ratios of $31,000 (80% UR, $27,000-$40,000) per YOLS for men and $39,000 (80% UR, $33,000-$53,000) per YOLS for women. First-year treatment costs of $940 million were the same as treating according to PBS criteria, but absolute health impact in terms of deaths averted and years of life saved was more than doubled. CONCLUSIONS: While PBS criteria do target patients at risk of CHD, there is room for improvement in identifying those most at risk of CHD, and treatment according to PBS criteria is not likely to be the most cost-effective. For optimal cost-effectiveness, targeting of therapy for primary CHD prevention needs to be based on population-specific, multivariable risk.     

Cost-effectiveness of antihyperlipemic therapy in the prevention of coronary heart disease. The case of cholestyramine

Using cholestyramine as a model, we considered the cost-effectiveness of antihyperlipemic therapy in the primary prevention of coronary heart disease among men between 35 and 74 years of age with elevated levels of total plasma cholesterol. Our findings indicate that the cost-effectiveness of treatment varies substantially, ranging from about $36,000 to over $1 million per year of life saved. Cost-effectiveness was highest for younger patients, for those with additional coronary risk factors (eg, smoking or hypertension), and for those whose course of therapy is of less-than-lifelong duration. Conversely, it is lowest for older patients, for those with no additional coronary risk factors, and for those who are treated for a lifetime. Our results suggest that pharmacologic therapy may not be cost-effective for all patients with elevated cholesterol levels, especially those over 65 years of age. For many younger patients, however--those with additional coronary risk factors and more severe elevations in cholesterol levels--the cost-effectiveness of therapy may be comparable with other accepted medical practices.     

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

OBJECTIVE: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. DESIGN: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. PATIENTS AND SETTING: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. MAIN OUTCOME MEASURES: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. RESULTS: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107 730 (95% CI, $68 626-$209 881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). CONCLUSIONS: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.     

Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol.

OBJECTIVE: To examine whether a small dose of bile acid sequestrant used in combination with a hydroxymethylglutaryl coenzyme A reductase inhibitor is more effective in reducing serum and low-density lipoprotein (LDL) cholesterol levels than inhibitor used alone. DESIGN: A randomised, double-blind study. SETTING: Subjects receiving tertiary care at a hospital lipid clinic. PATIENTS: Subjects with severe primary hypercholesterolaemia (types IIa and IIb), already stabilised on a cholesterol-lowering diet, with serum cholesterol levels of 7.0 mmol/L or more and triglyceride levels of 6.0 mmol/L or less. Sixty-four subjects were randomly assigned to the treatment groups; three withdrew before any outcome observations; 61 completed the trial and their results were analysed. INTERVENTIONS: Subjects were randomly assigned to receive either colestipol placebo or colestipol 5 g or 10 g each morning in fixed dosage for 18 weeks. They simultaneously received incremental doses of simvastatin: placebo for six weeks, then 20 mg/night for six weeks, then 40 mg/night for a final six weeks. MAIN OUTCOME MEASURES: Lipids, lipoproteins, and haematological and biochemical safety parameters were measured at the end of each treatment period. Adverse events were monitored. RESULTS: Respective maximum reductions (95% confidence intervals) in serum cholesterol, LDL cholesterol and apolipoprotein B (apo-B) values in subjects taking combination therapy were 41% (38%-45%), 50% (46%-53%) and 43% (39%-46%), compared with lesser reductions of 32% (26%-37%), 38% (31%-45%) and 37% (32%-41%) in those taking simvastatin monotherapy. The percentage changes in LDL cholesterol with combination therapy were independent of baseline cholesterol level or lipid phenotype. Combination therapy reduced serum triglyceride levels by up to 24% (15%-32%) and increased high-density lipoprotein (HDL) cholesterol levels by up to 9% (3%-15%). Three subjects withdrew within a few weeks because of severe gastrointestinal side effects related to colestipol; 19 experienced milder gastrointestinal side effects, 15 were taking combination therapy. CONCLUSIONS: A combination of low-dose colestipol and simvastatin was found to be more effective in reducing serum and LDL cholesterol than simvastatin used alone. Such combination therapy offers the possibility of improved cholesterol lowering without the need for full dosage of either drug.     

Hepatitis C: an economic evaluation of extended treatment with interferon.

OBJECTIVES: To re-evaluate the cost effectiveness of treating hepatitis C virus (HCV) infection with interferon alfa (IF alpha) in Australia, taking into account changes in clinical practice. DESIGN: A decision-analytic method (Markov model) was used to simulate the costs and effects of 6 months and 12 months of treatment with IF alpha versus no treatment (conventional management). Both costs and effects were modelled over 30 years. DATA SOURCES: Published meta-analysis of the effectiveness of treatment, professional judgement about treatment protocols, scheduled medical fees, diagnosis-related costs for hospital admission, and a literature search for quality-of-life weights. PATIENTS: A hypothetical cohort of 1000 patients with chronic HCV infection aged 40 years at the start of treatment. MAIN OUTCOME MEASURES: Incremental costs per life-year gained and per quality-adjusted life-year (QALY) gained. RESULTS: Compared with no treatment, IF alpha treatment for 6 months results in an extra 94.2 life-years or 320.1 QALYs at an extra cost of $1.8 million (after discounting at 3%) in a cohort of 1000 patients. Discounted cost per life-year gained is $19,110, which is about a quarter of the cost reported in 1994. The discounted cost per QALY gained is $5625. Extended treatment for another 6 months results in an additional 89.0 life-years saved or 170.8 QALYs gained at an incremental discounted cost of $15,835 per life-year gained and $8250 per QALY gained. CONCLUSIONS: The cost effectiveness of IF alpha treatment for HCV infection has improved as a result of better patient selection, cost reductions and enhanced effectiveness of extended treatment. The results are sensitive to assumptions made about quality of life and the discount rate.     

Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer. Estimates using decision analysis while awaiting clinical trial results.

OBJECTIVE--To assess the efficacy and cost-effectiveness of standard chemotherapy and high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in metastatic breast cancer. DESIGN--Decision analysis model using a Markov process. SETTING--Response and recurrence rates from the published literature for standard therapy and from case series of ABMT. Costs were based on local charges and on adjusted Medicare data. PATIENTS--Hypothetical cohorts of women with metastatic breast cancer who had no bone marrow involvement and no comorbid illness. INTERVENTION--The standard chemotherapy cohort received cyclophosphamide, doxorubicin, and fluorouracil. The ABMT cohort was treated with intense induction chemotherapy, then additional high-dose chemotherapy following a remission, with ABMT support. MAIN OUTCOME MEASURES--Anticipated survival, incremental cost per year of life, and incremental cost per quality-adjusted year of life gained using a 5-year time horizon. Rigorous sensitivity analyses were done, including assessing a benefit "tail" of normal life expectancy for those free of disease after 5 years. RESULTS--ABMT was the preferred approach under almost all assumptions, but the size of the benefit varied greatly. ABMT had a survival benefit of 6.0 months at 5 years at an incremental cost of $115,800 per year of life saved. If patients who were free of disease after 5 years had normal survival, the benefit was 18.1 months at an incremental cost of $28,600 per year. The benefit of ABMT was primarily dependent on whether the recurrence risk was constant or decreases after a finite period of time. CONCLUSION--Using reasonable assumptions, ABMT provided a substantial benefit but at a cost that may be untenable. Decision analysis highlights the limitations in the currently available data and the assumptions made for the emotional question of using ABMT in metastatic breast cancer. The model supports the need for randomized clinical trials.     

Nonionic contrast media: economic analysis and health policy development.

The replacement of old radiologic contrast media with supposedly safer but more expensive media has created a dilemma for radiologists and hospital administrators. To quantitate the nature of this trade-off we performed a cost-utility analysis using optimistic assumptions that favoured the new media. A complete conversion to the new media would result in an incremental cost of at least $65,000 to gain 1 quality-adjusted life-year (QALY). For a selective strategy in which only high-risk patients would receive the new media the cost would be about $23,000 per QALY gained. However, the incremental cost for low-risk patients is over $220,000 per QALY gained. Conversion to the new contrast media, although not necessarily the most efficient use of scarce resources, has already occurred in Ontario, primarily because of press publicity, pressure from insurers and a political unwillingness of policymakers to decide the fate of identifiable victims. We found that funding of a new intervention associated with a high cost-utility ratio rather than interventions with lower ratios might save some identifiable victims at the expense of a larger number of unidentifiable ones.     

Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.

OBJECTIVE: To assess the efficacy, safety and tolerability of pravastatin over three years of treatment. DESIGN: An open, multicentre randomised study. SETTING: Subjects receiving tertiary care at three hospital lipid clinics. PATIENTS: Subjects with primary hypercholesterolaemia (type IIa) or combined hyperlipidaemia (type IIb), already stabilised on a cholesterol-lowering diet, with low density lipoprotein (LDL) cholesterol levels of greater than 4.7 mmol/L and triglyceride levels of less than 4.5 mmol/L. Sixty-one subjects were randomly assigned to the treatment groups: 60 completed 12 weeks and 46 completed 30-36 months of treatment. INTERVENTIONS: Subjects were randomly assigned to receive either pravastatin 20 mg/day, pravastatin 40 mg/day or cholestyramine 16 g/day for a period of 12 weeks. Subsequently, dose titration of pravastatin up to 40 mg/day was permitted, if required, and all groups received supplementary therapy with other lipid-lowering drugs. MAIN OUTCOME MEASURES: Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored. RESULTS: There were significant reductions in total and LDL cholesterol levels with all treatments over 12 weeks (P < 0.001). The mean reductions (+/- SD) in LDL cholesterol were 26% +/- 14% in the group taking pravastatin 20 mg/day (n = 21), 30% +/- 8% in the group taking pravastatin 40 mg/day (n = 21) and 34% +/- 13% in the group taking resin (n = 18). The percentage changes in LDL cholesterol were independent of age, baseline cholesterol level or lipid phenotype. High density lipoprotein (HDL) cholesterol levels were significantly increased, by 8%-18% with all treatments (P < 0.001). Triglyceride levels were reduced by high-dose pravastatin only (7% +/- 29%), but were found to increase with resin (45% +/- 63%). During long-term treatment over 36 months, still greater reductions in total and LDL cholesterol were found in patients taking pravastatin (n = 35), but not in those taking resin (n = 11). There was an apparent decrease in effect beyond 18 months in both groups, possibly related to reduced compliance with diet or cholestyramine intake. Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events). Adverse events during 12 weeks' monotherapy with pravastatin included central nervous system (CNS) symptoms (12%), gastrointestinal (GIT) symptoms (7%) and an acute hepatitic reaction (one subject). Of those in the resin therapy group, 22% developed GIT symptoms. Myalgia occurred in three subjects using a combination of pravastatin and clofibrate, but this resolved fully upon clofibrate withdrawal. CONCLUSIONS: Pravastatin was found to be a relatively effective, safe and well tolerated lipid-lowering drug. Still greater LDL reduction was achieved with pravastatin combination therapy and this was essentially maintained over three years.     

The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in homosexual and bisexual HIV-positive men.

CONTEXT: Homosexual and bisexual men infected with human immunodeficiency virus (HIV) are at increased risk for human papillomavirus-related anal neoplasia and anal squamous cell carcinoma (SCC). OBJECTIVE: To estimate the clinical benefits and cost-effectiveness of screening HIV-positive homosexual and bisexual men foranal squamous intraepithelial lesions (ASIL) and anal SCC. DESIGN: Cost-effectiveness analysis performed from a societal perspective that used reference case recommendations from the Panel on Cost-Effectiveness in Health and Medicine. A state-transition Markov model was developed to calculate lifetime costs, life expectancy, and quality-adjusted life expectancy for no screening vs several screening strategies for ASIL and anal SCC using anal Papanicolaou (Pap) testing at different intervals. Values for incidence, progression, and regression of anal neoplasia; efficacy of screening and treatment; natural history of HIV; health-related quality of life; and costs were obtained from the literature. SETTING AND PARTICIPANTS: Hypothetical cohort of homosexual and bisexual HIV-positive men living in the United States. MAIN OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy, quality-adjusted years of life saved, lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Screening for ASIL increased quality-adjusted life expectancy at all stages of HIV disease. Screening with anal Pap tests every 2 years, beginning in early HIV disease (CD4 cell count >0.50 x 10(9)/L), resulted in a 2.7-month gain in quality-adjusted life expectancy for an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year saved. Screening with anal Pap tests yearly provided additional benefit at an incremental cost of $16,600 per quality-adjusted life year saved. If screening was not initiated until later in the course of HIV disease (CD4 cell count <0.50 x 10(9)/L), then yearly Pap test screening was preferred due to the greater amount of prevalent anal disease (cost-effectiveness ratio of less than $25,000 per quality-adjusted life year saved compared with no screening). Screening every 6 months provided little additional benefit over that of yearly screening. Results were most sensitive to the rate of progression of ASIL to anal SCC and the effectiveness of treatment of precancerous lesions. CONCLUSIONS: Screening HIV-positive homosexual and bisexual men for ASIL and anal SCC with anal Pap tests offers quality-adjusted life expectancy benefits at a cost comparable with other accepted clinical preventive interventions.     

Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness.

CONTEXT: Cervical cancer is a leading cause of cancer-related death among women in developing countries. In such low-resource settings, cytology-based screening is difficult to implement, and less complex strategies may offer additional options. OBJECTIVE: To assess the cost-effectiveness of several cervical cancer screening strategies using population-specific data. DESIGN AND SETTING: Cost-effectiveness analysis using a mathematical model and a hypothetical cohort of previously unscreened 30-year-old black South African women. Screening tests included direct visual inspection (DVI) of the cervix, cytologic methods, and testing for high-risk types of human papillomavirus (HPV) DNA. Strategies differed by number of clinical visits, screening frequency, and response to a positive test result. Data sources included a South African screening study, national surveys and fee schedules, and published literature. MAIN OUTCOME MEASURES: Years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (cost per YLS). RESULTS: When analyzing all strategies performed as a single lifetime screen at age 35 years compared with no screening, HPV testing followed by treatment of screen-positive women at a second visit, cost $39/YLS (27% cancer incidence reduction); DVI, coupled with immediate treatment of screen-positive women at the first visit was next most effective (26% cancer incidence reduction) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit was least effective (19% cancer incidence reduction) at a cost of $81/YLS. For any given screening frequency, when strategies were compared incrementally, HPV DNA testing generally was more effective but also more costly than DVI, and always was more effective and less costly than cytology. When comparing all strategies simultaneously across screening frequencies, DVI was the nondominated strategy up to a frequency of every 3 years (incremental cost-effectiveness ratio, $460/YLS), and HPV testing every 3 years (incremental cost-effectiveness ratio, $11 500/YLS) was the most effective strategy. CONCLUSION: Cervical cancer screening strategies that incorporate DVI or HPV DNA testing and eliminate colposcopy may offer attractive alternatives to cytology-based screening programs in low-resource settings.     

Probucol (Lorelco) in treatment of hyperlipemia.

The chemical structure of probucol differs from that of other hypolipemic agents, and its mechanism of action is unknown. This agent lowers elevated serum cholesterol (and low-density lipoprotein) levels and appears to be effective when used as an adjunct to a low-cholesterol, low-saturated-fat diet for treatment of type IIa hyperlipoproteinimia in adults; however, it is less effective than cholestyramine resin in patients with familial type IIa disorder. Although probucol has no consistent effect on elevated triglyceride levels, it may be useful as an adjunct to other drugs that lower these concentrations in patients with types IIb, III, and IV hyperlipoproteinemia when hypercholesterolemia persists. Probucol is generally well tolerated.     

The cost of intensive and special care of the newborn

The cost of providing intensive (level-3) and special (level-2) care for newborn infants in a tertiary perinatal service was determined prospectively and was expressed in 1984 Australian dollars. Direct costs that were expressed per occupied bed-day were $690 for level-3, high-dependency care; $421 for level-3, low-dependency care; $544 for over-all level-3 care; $242 for level-2, high-dependency care; $170 for level-2, low-dependency care; and $201 for over-all level-2 care. Each level of care generated additional costs of $42 per occupied bed-day. Taking these additional costs into account, the over-all occupied bed-day cost of level-3 and level-2 neonatal care was $339. The major components of this over-all cost were: nursing staff members, 50%; medical staff members, 11%; consumable and recyclable items, 12%; and diagnostic services, 8%.     

Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement.

OBJECTIVE: To compare the efficacy and cost-effectiveness of enoxaparin, a low-molecular-weight heparin derivative, with that of low-dose warfarin in the prevention of deep-vein thrombosis (DVT) after total hip replacement. DATA SOURCES: English-language articles on enoxaparin and warfarin prophylaxis is patients undergoing total hip replacement published from January 1982 to December 1992. STUDY SELECTION: Four trials of enoxaparin (involving 567 patients) and six trials of warfarin (involving 630) met the following criteria: randomized controlled trial, prophylaxis started no later than 24 hours after surgery and continued for at least 7 days, warfarin dose monitored and adjusted appropriately, enoxaparin dosage 30 mg twice daily, and DVT confirmed by bilateral venography. DATA EXTRACTION: Rates of DVT, cost of prophylaxis, diagnosis and treatment per patient, rate of pulmonary embolism (PE), number of deaths and incremental cost-effectiveness (cost per life-year gained). DATA SYNTHESIS: The pooled rate of DVT was 13.6% with enoxaparin (95% confidence interval [CI] 10.9% to 16.3%) and 20.6% with warfarin (95% CI 17.4% to 23.8%). At a cost of $19.55 per day for enoxaparin the total cost per patient, including prophylaxis and management of DVT, exceeded that per patient receiving warfarin by about $121. For every 10,000 patients treated the use of enoxaparin will prevent 47 cases of DVT, 3 cases of PE and 4 deaths. Thus, the estimated incremental cost-effectiveness of enoxaparin is $29 120 per life-year gained. CONCLUSION: On the basis of current Canadian cost-effectiveness guidelines the results of this study would be considered moderate to strong evidence to adopt enoxaparin prophylaxis against DVT after total hip replacement. However, because of the limited data the estimates are uncertain. Future trials should compare enoxaparin and warfarin and incorporate a prospective economic appraisal.     

Benefits and costs of using HPV testing to screen for cervical cancer

CONTEXT: Despite quality assurance standards, Papanicolaou (Pap) test characteristics remain less than optimal. OBJECTIVE: To compare the societal costs and benefits of human papillomavirus (HPV) testing, Pap testing, and their combination to screen for cervical cancer. DESIGN, SETTING, AND POPULATION: A simulation model of neoplasia natural history was used to estimate the societal costs and quality-adjusted life expectancy associated with 18 different general population screening strategies: Pap plus HPV testing, Pap testing alone, and HPV testing alone every 2 or 3 years among hypothetical longitudinal cohorts of US women beginning at age 20 years and continuing to 65 years, 75 years, or death. MAIN OUTCOME MEASURE: Discounted costs per quality-adjusted life-year (QALY) saved of each screening strategy. RESULTS: Maximal savings in lives were achieved by screening every 2 years until death with combined HPV and Pap testing at an incremental cost of $76 183 per QALY compared with Pap testing alone every 2 years. Stopping biennial screening with HPV and Pap testing at age 75 years captures 97.8% of the benefits of lifetime screening at a cost of $70 347 per QALY. Combined biennial HPV and Pap testing to age 65 years captures 86.6% of the benefits achievable by continuing to screen until age 75 years. Human papillomavirus screening alone was equally effective as Pap testing alone at any given screening interval or age of screening cessation but was more costly and therefore was dominated. In sensitivity analyses, HPV testing would be more effective and less costly than Pap testing at a cost threshold of $5 for an HPV test. CONCLUSIONS: Screening with HPV plus Pap tests every 2 years appears to save additional years of life at reasonable costs compared with Pap testing alone. Applying age limits to screening is a viable option to maintain benefits while reducing costs.     

Are clinical trials a cost-effective investment?

To assess the economic attractiveness of clinical research, this study measures the cost-effectiveness of seven selected randomized trials. The model considers the cost of performing a trial and the benefits to the health status of a target population one could expect before the trial was performed. The incremental cost-effectiveness for performing the trials ranged from a low of $2 to $3 per life-year saved for a trial of aspirin in unstable angina to a high of $396 to $685 per life-year saved for the randomized trial portion of the Coronary Artery Surgery Study. These ratios were substantially lower (ie, more economically attractive) than the cost-effectiveness ratios associated with performing interventions of proved effectiveness. This study shows that a selected group of clinical trials, some of which were controversial and expensive, were indeed a good investment. This information may be helpful to policymakers who consider allocating funds to biomedical research.     

Long-term cost-effectiveness of various initial monotherapies for mild to moderate hypertension

To evaluate the comparative efficacy and cost-effectiveness of various antihypertensive medications in persons aged 35 through 64 years with diastolic blood pressure of 95 mm Hg or greater and no known coronary heart disease, we used the Coronary Heart Disease Policy Model, which is a computer simulation of overall mortality as well as the mortality, morbidity, and cost of coronary heart disease in the US population. From the pooled literature, we estimated the antihypertensive and total cholesterol effects of various antihypertensive regimens. For 20 years of simulated therapy from 1990 through 2010, the cost per year of life saved was projected to be $10,900 for propranolol hydrochloride; $16,400 for hydrochlorothiazide; $31,600 for nifedipine; $61,900 for prazosin hydrochloride; and $72,100 for captopril. Doubling the cholesterol effects of the agents under study did not significantly change their effectiveness because, in general, lowering diastolic blood pressure by 1 mm Hg was equivalent to lowering the cholesterol level by 6%. Although any projection requires multiple estimates, each of which may be open to debate, propranolol appears to be the preferred initial option under most of a variety of alternative assumptions.