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Drugs are becoming a particular target for health care cost containment measures, as part of the increasing pressure to improve the value for money from the use of health care resources. This has led to an exponential growth in the number of economic evaluations of pharmaceuticals, many of which have been funded by pharmaceutical companies. A review of the existing literature on economic evaluation of pharmaceuticals was conducted in order to classify studies and to document their results. The review identified 85 evaluations, published between 1986 and 1991, that were suitable for analysis. In most published studies it was found that in the treatment or prevention of a disease, a drug intervention was more cost-effective than no intervention and, in a number of cases, drug interventions were at least as cost-effective as other forms of intervention. In evaluating the published evidence it is important to note that positive studies are more likely to be published and that the quality of study methods varies. However, the studies can be of use to policy makers with an interest in securing more value for money, although economic assessments should be applied equally to all health technologies.

OBJECTIVE: Using data from the Canadian Bronchiolitis Epinephrine Steroid Trial we assessed the cost-effectiveness of treatments with epinephrine and dexamethasone for infants between 6 weeks and 12 months of age with bronchiolitis. METHODS: An economic evaluation was conducted from both the societal and health care system perspectives including all costs during 22 days after enrollment. The effectiveness of therapy was measured by the duration of symptoms of feeding problems, sleeping problems, coughing, and noisy breathing. Comparators were nebulized epinephrine plus oral dexamethasone, nebulized epinephrine alone, oral dexamethasone alone, and no active treatment. Uncertainty around estimates was assessed through nonparametric bootstrapping. RESULTS: The combination of nebulized epinephrine plus oral dexamethasone was dominant over the other 3 comparators in that it was both the most effective and least costly. Average societal costs were $1115 (95% credible interval [CI]: 919–1325) for the combination therapy, $1210 (95% CI: 1004–1441) for no active treatment, $1322 (95% CI: 1093–1571) for epinephrine alone, and $1360 (95% CI: 1124–1624) for dexamethasone alone. The average time to curtailment of all symptoms was 12.1 days (95% CI: 11–13) for the combination therapy, 12.7 days (95% CI: 12–13) for no active treatment, 13.0 days (95% CI: 12–14) for epinephrine alone, and 12.6 days (95% CI: 12–13) for dexamethasone alone. CONCLUSION: Treating infants with bronchiolitis with a combination of nebulized epinephrine plus oral dexamethasone is the most cost-effective treatment option, because it is the most effective in controlling symptoms and is associated with the least costs.

We describe a method we developed for estimating cancer costs from the perspective of patients and caregivers and evidence supporting validity of estimates obtained. To increase validity, interview questions were anchored to treatments; costs were divided into their components; most questions focused on facts; and the research team combined responses into cost estimates. Evidence for validity comes from a prospective study of breast cancer costs using this method. Estimates obtained using interview responses were similar to those from independent sources. Women reported being reimbursed $205 on average for prosthesis (government reimbursement = $200); paying $15.48 per night at cancer lodge (average rate = $17.52); receiving government illness insurance for 14.6 weeks at 53% of usual salary (governmental program covers 15 weeks at 55%). A priori hypotheses about relations of costs with other characteristics were also confirmed. For example, patients’ weekly travel costs increased as a function of distance from the radiotherapy center, with patients living

Hip fractures are a major cause of morbidity for older women, which result in impaired health related quality of life (HRQOL). Few studies have prospectively evaluated the effect of hip fractures in women on HRQOL with different health state preference measures. We compared how 4 different preference measures change in women post-hip fracture and evaluated the responsiveness of the preference measures. We also compared HRQOL in women with recent hip fractures to a control sample at baseline and to normative Canadian data at followup.Health status measures [the Medical Outcomes Study Short Form-36 (SF-36)] and preferences (direct and indirect) of women over age 50 years with hip fractures were measured at baseline and at 3 and 9 months. Baseline preferences [Health Utilities Index (HUI), Feeling Thermometer, Standard Gamble, and SF-36] were obtained from women without hip fractures for comparison. Independent sample t tests were used to compare baseline scores of fracture and nonfracture controls. Correlations between preference and health status measures were assessed and repeated measures ANOVA was used to assess change in health status and preferences over time.Health status and preference measures were lower in women with hip fractures in comparison to nonfracture controls. After 9 months, the SF-36, HUI, Feeling Thermometer, and SF-6D scores improved significantly. Values for the SF-36 remained lower than an age-matched normative sample. The HUI and SF-6D were sensitive to change over time, but the Standard Gamble was not.HRQOL and preference measures improve over time in women with recent hip fractures, with the majority of the change occurring in the initial 3 months. Our results suggest that the HUI and SF-6D are valid measures to assess change over time post-hip fracture.

Background Secondary prevention through cardiac rehabilitation (CR) has been recommended for most patients with coronary artery disease (CAD). Although generally reimbursed for 3 months, to date, optimal CR program duration and frequency of patient contact has yet to be identified. This study compared standard (33 sessions for 3 months) versus distributed (33 sessions for 12 months) CR for effects on exercise variables, risk factors, health-related quality of life (HRQL), depressive symptoms, and direct costs to the cardiac health care system. Methods We randomly assigned 392 patients to either standard CR (n = 196) or distributed CR (n = 196). Outcomes were cardiorespiratory fitness, daily physical activity, coronary risk factors, generic and heart disease HRQL, and depressive symptoms, measured 12 and 24 months after program intake. Secondary outcomes included these variables measured after 3 months. Costs to the cardiac health care system were determined 2 years after program initiation. Results Both groups showed improvements over time in cardiorespiratory fitness, daily physical activity, low-density lipoprotein cholesterol, generic and heart disease HRQL, and depressive symptoms. Over time, blood pressure and body mass index values worsened. Smoking status, high-density lipoprotein cholesterol, and triglyceride levels remained unchanged. There were no clinically meaningful or statistically significant between group differences for outcomes at 12 or 24 months. The costs of the programs to the cardiac health care system were not different. Conclusions From a clinical standpoint, this study indicates that both standard and distributed program formats serve patients with CAD equally well over the longer term. Programs could use either program delivery model (standard or distributed) depending on patient or program needs. Costs to the cardiac health care system are similar.

This Canadian hepatitis C model estimates economic burden of disease using Markov modeling to predict progression over 11 health states annually from 2001 to 2040. Incidence-based estimates help demonstrate the capability to determine cost-effectiveness of programs to prevent different proportions of incident cases. Benefits of prevention increase linearly with the number of incident cases prevented. The model forecasts annual health care costs for the treatment of HCV-related disease ranging from $103 to $158 million over time. Health care costs attributable to 2001 incidence cohort are forecast at $14.6 million for prevention. The increasing cost of HCV provides a framework for further analysis and implementation of long-term policies aimed at appropriate allocation of resources for health in Canada.

PURPOSE To evaluate patient safety, catheter rupture rates, and computed tomography (CT) image quality when using peripherally inserted central catheters (PICCs) in vivo for the power injection of CT contrast media at standard injection rates. MATERIALS AND METHODS A prospective study to evaluate the safety and effectiveness of power injection of contrast media via indwelling PICCs was performed. Single-lumen and double-lumen polyurethane PICCs (5 F) were injected in vivo with contrast media for clinical CT examinations at injection rates ranging from 1 mL/sec to 4 mL/sec. Data collected included PICC rupture rate, patient complications, injection rate, peak injection pressure, PICC length, PICC age, and quality of contrast enhancement on the CT images. RESULTS One hundred ten power injections of PICCs for CT examinations were performed. There were 12 injections of single-lumen PICCs and 98 injections of double-lumen PICCs. The most common injection rate was 2 mL/sec, accounting for 89 of the 110 injections (81%). Two PICCs ruptured during power injection, both as a result of operator error. One of the PICCs that ruptured was clamped at the time of injection and the other one was kinked at its venous entry site. One additional PICC showed evidence of dysfunction; it ballooned without actually rupturing. No significant patient complications occurred. Contrast enhancement of the CT images was subjectively rated as average or above average in 95% of cases. CONCLUSIONS Contrast media can be power-injected via PICCs for routine CT examinations at a rate of 2 mL/sec, yielding satisfactory image quality without exposing patients to significant additional risk. Power injection rates greater than 2 mL/sec, as are typically used in CT angiography applications, were not fully evaluated by this study.

Irbesartan has been shown to reduce the doubling of serum creatinine (a strong predictor of progression to end-stage renal disease), the onset of end-stage renal disease and all-cause mortality in patients with type 2 diabetes when compared with standard care and amlodipine.The present study assessed the cost effectiveness of irbesartan, an angiotensin II receptor antagonist, and amlodipine, a calcium channel blocker, in the treatment of Canadian patients with diabetic nephropathy and hypertension.The analysis was conducted based on a Markov model using Monte Carlo simulation analysis to estimate the expected values for outcomes of interest. Transition probabilities were obtained from a comparative trial of amlodipine, irbesartan and standard care (antihypertensive treatment excluding other angiotensin II receptor antagonists or calcium channel blockers) in patients with overt diabetic nephropathy and hypertension. Canadian costs for the health states studied were obtained from published data.Based on the results of the Monte Carlo simulation, irbesartan was dominant over standard care and amlodipine because it both reduces costs and leads to greater life expectancy. The incremental cost-effectiveness ratio for amlodipine in comparison with standard care was 102,000 dollars. Estimates of net benefit were correlated with transition probabilities relating to progression from the initial health state. The results were insensitive to univariate sensitivity analysis.Irbesartan use would lead to a reduction in medical costs and an increase in life expectancy when compared with amlodipine or standard care.

Rising health care costs, expensive new health care technologies and increasing patient expectations are placing huge pressures on the publicly funded health care system in Canada. As a result, policy makers need information on the cost and cost-effectiveness of new therapies in addition to their clinical benefits. In response to this need, the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) established a Working Group on Economic Analysis (WGEA) to provide advice on the economic evaluation of new cancer therapies. This article describes the WGEA's recommendations on which trials should be considered for concurrent analysis of economic, as well as related issues, such as the number of patients required for an economic analysis within a prospective clinical trial and the selection of participating centres. The recommendations in this document are meant to be pragmatic, as the WGEA recognizes that both the research funds and human resource capacity for this type of research in Canada are limited. These recommendations are currently guiding priority setting with regard to trials for economic evaluation in NCIC trials. Examples of how these recommendations have been applied to actual trials are presented.

Air pollution and premature death are important public health concerns. Analyses have repeatedly demonstrated that airborne particles are associated with increased mortality and estimates have been used to forecast the impact on life expectancy. In this analysis, we draw upon data from the American Cancer Society (ACS) cohort and literature on utility-based measures of quality of life in relation to health status to more fully quantify the effects of air pollution on mortality in terms of quality-adjusted life expectancy. The analysis was conducted within a decision analytic model using Monte Carlo simulation techniques. Outcomes were estimated based on projections of the Canadian population. A one-unit reduction in sulfate air pollution would yield a mean annual increase in Quality-Adjusted Life Years (QALYs) of 20,960, with gains being greater for individuals with lower educational status and for males compared to females. This suggests that the impact of reductions in sulfate air pollution on quality-adjusted life expectancy is substantial. Interpretation of the results is unclear. However, the potential gains in QALYs from reduced air pollutants can be contrasted to the costs of policies to bring about such reductions. Based on a tentative threshold for the value of health benefits, analysis suggests that an investment in Canada of over 1 billion dollars per annum would be an efficient use of resources if it could be demonstrated that this would reduce sulfate concentrations in ambient air by 1 microg/m(3). Further analysis can assess the efficiency of targeting such initiatives to communities that are most likely to benefit.

To determine whether statins are underprescribed in the Canadian military. The cost effectiveness of statin therapy in patients identified by the 1998 Canadian cholesterol interim guidelines was also explored.Charts of 1424 Canadian military personnel (age 45 or older) were reviewed at 11 Canadian bases. Risk factors and cholesterol values were used to identify drug therapy candidates. Cost effectiveness ratios and health benefits in terms of years of life saved for statin therapy were estimated for the candidates using a validated cardiovascular disease life expectancy model.Of the 1313 personnel not on lipid lowering medication, 172 were identified as drug therapy candidates. An average of 2.89 years of life saved was forecast for the identified personnel, at an average cost of less than 10,000 dollars per year of life saved.The health benefits of statin therapy in this population are substantial and the cost effectiveness is acceptable. Statin therapy warrants greater attention as a preventive strategy for coronary artery disease.

ObjectiveThe objective was to assess the impact of different levels of risk of disease on a woman's preferences for health states. Women were provided with health scenarios incorporating different levels of lifetime risks for breast cancer, hip fracture, and coronary heart disease (CHD). In this way, we were able to determine the incremental effect of changes in risks of each disease on preference values.Methods and DataPreference values and utility scores were obtained for six health scenarios by both the feeling thermometer (FT) and standard gamble (SG) methods. Scenarios presented the different lifetime risks of CHD, breast cancer, and hip fracture associated with and not associated with long-term use of hormone replacement therapy (HRT) and raloxifene. Risks of breast cancer were based on perceived risks and population risks. The sample population consisted of 40 healthy female volunteers aged between 45 and 65 years randomly selected from the Ottawa-Carleton district.ResultsBased on their perceived risk of breast cancer, the women had higher value scores for the raloxifene risk profile than for both HRT (p = .002) and no therapy (p = .003), with similar results for analyses based on population risks and from utility scores. Regression analysis showed that the risk of breast cancer (p

Rheumatoid arthritis is one of the most common chronic systemic inflammatory diseases, affecting approximately 1% of the adult population. Disease-modifying antirheumatic drugs (DMARDs) have been the mainstay of treatment for rheumatoid arthritis when combined with physical therapy and aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory drugs. Recently, a number of new biological therapies have been introduced for the treatment of this condition and will have a major impact on the future management of this disabling disease. In this review, we summarise data on the efficacy and tolerability of the currently available DMARDs, including gold compounds, antimalarials, penicillamine, cytotoxic drugs (azathioprine and cyclophosphamide), sulfasalazine, methotrexate, leflunomide, cyclosporin, anti-tumour necrosis factor agents, combination therapy and apheresis. A literature review and quality assessment of economic evaluations of DMARDs is presented, illustrating that there has been a paucity of economic evaluations on these agents and showing the variable quality of those studies that are available. The manuscript also addresses the pharmacoeconomic implications of the new agents for rheumatoid arthritis; the need for formal long term economic evaluations in order to determine the cost effectiveness of these costly, but highly effective, new treatments is emphasised.

Objective.To examine the effectiveness of a home visit program to improve home safety and decrease the frequency of injury in children. We examined the effects of the program on 1) parental injury awareness and knowledge; 2) the extent that families used home safety measures; 3) the rate of injury; and 4) the cost effectiveness of the intervention.Design.A randomized, controlled trial.Setting.A multicenter trial conducted at 5 hospitals in 4 Canadian urban centers.Participants.Children Intervention.Subsequent to a home inspection conducted to determine baseline hazard rates for both groups, participants in the intervention group received a single home visit that included the provision of an information package, discount coupons, and specific instruction regarding home safety measures.Main Results.The median age was 2 years, with males comprising ∼60% of participants. The experimental groups were comparable at outset in terms of case-control status, age, gender, and socioeconomic status. Parental injury awareness and knowledge was high; 73% correctly identified injury as the leading cause of death in children, and an intervention effect was not demonstrated. The adjusted odds ratios (ORs) for the home inspection items indicated that significant safety modifications only occurred in the number of homes having hot water not exceeding 54°C (OR: 1.31, 95% confidence interval [CI]: 1.14, 1.50) or the presence of a smoke detector (OR: 1.45, 95% CI: 0.94, 2.22). However, the intervention group reported home safety modifications of 62% at 4 months and significantly less injury visits to the doctor compared with the nonintervention group (rate ratio: 0.75; 95% CI: 0.58, 0.96). The total costs of care for injuries were significantly lower in the intervention group compared with the nonintervention group with a cost of $372 per injury prevented.Conclusions.An intervention using a single home visit to improve the extent to which families use safety measures was found to be insufficient to influence the long-term adoption of home safety measures, but was effective to decrease the overall occurrence of injuries. Future programs should target a few, well-focused, evidence-based areas including the evaluation of high-risk groups and the effect of repeated visits on outcome.

Objectives: Assessments of health technologies increasingly include economic evaluations conducted alongside clinical trials. One particular concern with economic evaluations conducted alongside clinical trials is the generalizability of results from one setting to another. Much of the focus relating to this topic has been on the generalizability of results between countries. However, the characteristics of clinical trial design require further consideration of the generalizability of cost data between centers within a single country, which could be important in decisions about adoption of the new technology.Methods: We used data from a multicenter clinical trial conducted in the United Kingdom to assess the degree of variation in costs between patients and between treatment centers and the determinants of the degree of such variation.Results: The variation between patients was statistically significant for both the experimental and conventional treatments. However, the degree of variation between centers was only statistically significant for the experimental treatment. Such variation appeared to be a result of hospital practice, such as payment mechanisms for staff and provision of hostel accommodation, rather than variations in physical resource use or substantive differences in cost structure.Conclusions: Multicenter economic evaluations are necessary for determining the variations in hospital practice and characteristics that can in turn determine the generalizability of study results to other settings. Such analyses can identify issues that may be important in adopting a new health technology. Analysis is required of similar large multicenter trials to confirm these conclusions.

Objective: The objective of this study was to assess the cost effectiveness of using epoetin-α (erythropoietin) to augment preoperative autologous donation (PAD) of blood prior to elective cardiac surgery. Design and setting: We designed a decision-analytic model incorporating the risk of receiving allogeneic blood, the costs of blood products, the likelihood of developing transfusion-related diseases, the costs of transfusion-related diseases and their impact on life expectancy, and the effect of epoetin-α on the probability of transfusion. Interventions: The efficacy of epoetin-α was derived from data from a meta-analysis of published randomised trials comparing the use of epoetin-α to augment PAD with the use of PAD alone. Estimates for the other parameters were obtained by a systematic review of the literature. Main outcome measures and results: The use of epoetin-α reduced the proportion of patients receiving allogeneic transfusions by 60% (from 31.6 to 12.7%). However, this led to only a modest benefit of 0.000035 life years gained per patient and an incremental cost per life year gained of $Can44.6 million (1998 Canadian dollars). A detailed sensitivity analysis confirmed that the cost-effectiveness ratio was larger than that which is generally considered acceptable. Conclusions: Our study indicates that the use of epoetin-α to reduce perioperative allogeneic transfusions in cardiac surgery is not cost effective.

Background. Decision analysis (DA) and the probability-tradeoff technique (PTOT) are patient preference-based methods of determining optimal therapy for individuals. Using aspirin therapy for the primary prevention of stroke and myocardial infarction (MI) in elderly persons as an example, the objective of this study was to determine whether group-level treatment thresholds and individual-level treatment recommendations derived using PTOT are identical to those of DA incorporating the patients' own values. Methods. Persons in a pilot study of the efficacy of aspirin in the prevention of stroke and MI were asked to participate. Participant values and utilities for pertinent health states (e.g., minor and major stroke, MI, major bleeding episode) were determined. Then, in three hypothetical clinical situations in which the chance of stroke or MI was varied, PTOT was used to directly determine treatment thresholds for aspirin therapy (i.e., the smallest reduction in MI or stroke risk for which participants would be willing to take aspirin). Using DA modeling, with the same probabilities of events as in the PTOT exercise and incorporating participants' own values, treatment thresholds for the three clinical situations were determined. The thresholds determined by the two approaches were compared. Finally, based on these treatment thresholds, using the best estimates of the efficacy of aspirin to prevent first-time stroke and MI, PTOT and DA treatment recommendations for individual participants were compared. Results. The 42 participants reported that a major stroke was the least desirable health state, followed by MI, minor stroke, and major bleeding. The minimum risk reduction required to take aspirin was greater for MI prevention compared with stroke prevention. For the two clinical situations in which the hypothetical efficacy of aspirin to prevent stroke was varied, treatment thresholds for the PTOT versus DA approaches differed (p < 0.04), but this difference was not significant (p = 0.19) for the MI-based clinical situation. Using the best estimate of the efficacy of aspirin to prevent first-time stroke and MI, PTOT and DA treatment recommendations whether or not to take aspirin were discordant for 38% of participants (16 of 42) (p < 0.001). Conclusions. Patient preference-based group-level treatment thresholds and individual-level treatment recommendations can differ significantly depending on whether PTOT or DA is used, apparently because the two emphasize different aspects of the decision-making process. DA theory assumes that effective therapeutic decision making should maximize both quality and quantity of life; with PTOT, the emphasis for effective clinical decision making allows patients to be fully engaged in the process, thus hopefully leading to fully informed decisions that may result in satisfaction and compliance. Key words: decision making; decision analysis; patient preferences; treatment thresholds. (Med Decis Making 2000;20:394-403)

Background: Best supportive care has long been considered to be the standard therapy for metastatic non-small-cell lung cancer (NSCLC). There is now evidence from randomized trials that a number of chemotherapy regimens can palliate cancer-related symptoms and modestly improve survival. We show how cost-effectiveness analyses can be used to make choices between different (ambulatory) chemotherapy regimens. Methods: Clinical algorithms describing the diagnosis, staging, and treatment of metastatic NSCLC were incorporated into Statistics Canada’s Population Health Model. Using consistent methodology, we assessed the costeffectiveness of several chemotherapeutic interventions: a combination of vindesine (VDS) plus cisplatin, etoposide (VP-16) plus cisplatin, vinblastine (VLB) plus cisplatin, vinorelbine (Navelbine; NVB) plus cisplatin, paclitaxel (Taxol) plus cisplatin, and gemcitabine (GEM) and NVB alone. We calculated the total chemotherapy costs in 1995 Canadian dollars, the cost per case, the average life-years saved, and the cost per life-year saved. Using the Population Health Model, we then constructed an advanced decision framework that rank-ordered the various treatment regimens so as to optimize benefit below various cost-effectiveness thresholds. Results: One regimen (VLB plus cisplatin) appears to result in better survival and lower health care expenditures than best supportive care. By use of costeffectiveness thresholds of $25 000 and $50 000 per life-year gained, NVB plus cisplatin is the preferred regimen. When quality of life is considered, however, GEM is preferred to NVB plus cisplatin at a threshold value of $50 000. At thresholds of $75 000 and $100 000, paclitaxel plus cisplatin at a dose of 135 mg/m 2 is the preferred regimen. At thresholds of $50 000 and above, best supportive care is the least preferred regimen. Conclusions: This decision framework allows the comparison of different treatment regimens based on various cost-effectiveness thresholds. Our analysis also supports the use of chemotherapy regimens and the abandonment of best supportive care as the standard of care for patients with advanced NSCLC. [J Natl Cancer Inst 2000;92:1321–9].

Objectives: Due to the paucity and incompleteness of routine databases, many areas of health services research rely on the accuracy of individuals' recollections of health service encounters. The objective of this study is to explore differences between patient and physician recall of health care resource use by employing data from two randomized controlled trials. Methods: Data on the frequency of use of community-based health services were reported by both patients and their general practitioners (GPs) at three-month intervals for the first year after randomization. Analysis compared the completeness of data collected, the level of agreement between GPs and patients and differences in the estimated cost of community services. Further analysis assessed the impact of patient characteristics on reporting. Results: Data provided by GPs were less likely to be complete than patient data. There were significant differences between GPs and patients in their reported use of certain community services, particularly in relation to GP—patient contacts. However, this did not lead to significant differences in estimates of costs. Patient characteristics influenced the level of agreement with GPs, but not the proportion of forms completed. Conclusions: In research in which the use of community resources is a major component of costs, differential estimates of resource use may influence study results. Further research is required to identify optimal data collection methods for health service encounters. Where possible, studies should incorporate estimates of resource use from a variety of sources and conduct sensitivity analyses to assess the robustness of the results.

Background: The objective was to determine the average cost per quality-adjusted life year (QALY) gained of treating trauma victims at a tertiary trauma hospital and to determine the cost-effectiveness of trauma care at this center. The setting was a tertiary trauma center in the province of Ontario, Canada. The study population consisted of consecutive trauma admissions with ISS > 12 from April, 1994 to April, 1996. The study was of a retrospective cohort design with a cross-sectional survey. Methods: The hospital perspective was taken. Costs were determined from a retrospective cohort using a hospital-based case-costing system. Utility estimates for calculation of QALYs gained were obtained using a cross-sectional survey design. Cost-effectiveness was determined by estimating the incremental cost/QALY attributable to treatment at the trauma center. Sensitivity analysis was employed to vary assumptions about the proportion of costs and increased survival. Results: 484 patients with a median age of 39 years and a median ISS of 22 were studied. The average cost per QALY was $1,721, with a maximum value of $3,861. The increase in cost per QALY gained for treatment in a tertiary care center as opposed to a nontrauma center was $4,303, assuming a 20% increase in survival and assuming that the existence of the center increased the cost of care by 50%. The incremental cost/QALY ranged from $191 to $15,492 in the sensitivity analysis varying assumptions about the increased proportion of costs and survival attributable to care at the tertiary trauma center. Conclusions: This is the first economic evaluation of tertiary trauma care which includes both costs as opposed to charges as well as estimates of the QALYs gained. The results suggest that tertiary trauma care is cost-effective and less costly than treatment programs for other disease conditions when the quality-adjusted life years gained are included in the evaluation.

This chapter is concerned with the provision of palliative care. Palliative derives from the Latin word pallium, meaning a cloak or cover. In this context it refers to the provision of active care for a person whose condition is not responsive to curative treatment. A more developed definition is that palliative care is

Importance Future funding for new treatments in venous thromboembolism will be guided by cost-utility analyses. There is little available information on the utility of acute venous thromboembolism, limiting the validity of economic analyses. Objective To measure the quality of life in the health states relating to thromboembolism cost-utility analyses. Design A prospective cohort study. Setting A single-center, university-affiliated thrombosis clinic. Participants Two hundred sixteen thrombosis clinic patients with a history of lower limb deep vein thrombosis (DVT) or pulmonary embolism (PE). Exposures Participants consented to take a standard gamble interview. Each participant rated the quality of life in acute DVT, acute PE, and bleeding complication health states. Main Outcomes and Measures The standard gamble measured quality of life (utility value) for acute DVT, acute PE, major intracranial bleeding event, minor intracranial bleeding event, and gastrointestinal bleeding event. Results Two hundred fifteen responses were included in the analysis. Twenty-six percent had experienced both PE and DVT; 54%, DVT alone; and 20%, PE alone. Forty-two percent had experienced more than 1 episode of thrombosis, and 23% had had cancer-associated thrombosis. We found the median utility for acute DVT was 0.81 (interquartile range [IQR], 0.55-0.94); acute PE, 0.75 (IQR, 0.45-0.91); major intracranial bleeding event, 0.15 (IQR, 0.00-0.65); minor intracranial bleeding event, 0.75 (IQR, 0.55-0.92); and gastrointestinal bleeding event, 0.65 (IQR, 0.15-0.86). The median length of symptoms for DVT or PE was 1 week (IQR, Conclusions and Relevance To our knowledge, this is the largest published study on utilities in which the participants had personal experience of venous thromboembolism. We present unique information for economic analyses but have also identified future challenges for research in this area. Our summary results differ from those previously published, and we found wide variation in individual responses.

Arguments are being made more frequently to incorporate economic evaluations and quality of life assessments into clinical trials. Using two randomised, multicentre trials of radiotherapy for cancer as an example, this paper outlines: (1) the importance of including such assessments; (2) the practical considerations associated with the design of such trials; (3) the methods for collecting resource use and quality of life data; and (4) how such data can be used. Finally, it is emphasised that the anticipated benefits of collecting data relating to resource use and quality of life should outweigh the associated costs to research funding organisations.

Although there is a substantial amount of literature recording the increasing number of economic evaluations of health care interventions, there is little discussion of the level of impact such studies have had on decision-making. In this paper the evidence relating to impact which does exist is examined. The implication from this is that social science research has made little direct impact on health care decision-making. Theories relating to the process of research utilisation in decision-making are examined to ascertain why research may fail to be of influence. This leads to the conclusion that a major determinant of the level of impact made by research are the actions of the researchers. This paper concludes with the recommendations to researchers on how to increase the level of influence made by studies.

In most economic evaluations, future monetary costs and benefits and future health benefits are discounted at the same rate. The purpose of this article is to question such current practice. The primary reason behind discounting costs and benefits is to allow for individuals' preferences over the timing of such events, i.e. to represent social time preference. We argue that the social time preference rate for health benefits is unlikely to be the same as that for monetary costs and benefits. The results of a sensitivity analysis of pharmacoeconomic analyses of drug treatments for hypertension illustrate how the choice of discount rate can affect the conclusions. As no definite conclusions can be drawn regarding the magnitude of the discount rate for health benefits, we recommend that analysts conduct sensitivity analyses employing differential discount rates for health benefits as well as monetary costs and benefits.

AC proph after OS results in a decrease in the incidence of VTE with an associated increase in the risk of major bleeding (MB). Several AC agents and schedules are used; however the optimal timing of initiation has not been determined. It is likely that the proximity to the time of surgery might influence both the efficacy and safety of the AC thus altering their risk-benefit profile. Using a clinical cost-effectiveness approach we compared different AC and timings of VTE proph in patients undergoing OS. A meta-analysis of 55 randomized trials was done to estimate the risk (MB) and benefit (averted VTE) of proph in OS using placebo (plac) or different AC (ximelagatranxim, low molecular weight heparin-LMWH, unfractionated heparin-UFH, warfarin-warf and fondaparinux-fonda) and timings of initiation (defined as preoperative (preop) if the first dose of the AC was administered >2 hrs before surgery, perioperative (periop)if between 2 hrs before or up to 12 hrs after the surgery and postoperative (postop) if starting 12 hrs or more after surgery). Means and variances of the MB and VTE estimates were used to parameterize Monte Carlo simulations for a beta distribution using 1,000 replications. Incremental risk, benefit and risk-benefit ratios (compared to placebo) were calculated from the replications. All AC/timing combinations were compared across a range of benefit-risk tradeoff values (risk acceptance) by calculating the percentage of replications with the highest net clinical benefit (NCB; e.g. incremental benefit - incremental risk · tradeoff) for each AC/timing combination. A higher NCB represents a better risk-benefit profile. In addition all anticoagulants were pooled together according to the initial timing of administration and NCB was calculated using random re-sampling of the replications. Analyses were done separately for major VTE (mVTE; proximal deep vein thrombosis (DVT) + pulmonary embolism), and total VTE (tVTE; mVTE + distal DVT) and a sensitivity analysis was done after excluding xim. The reference tradeoff was estimated from the case-fatality rate-ratios of VTE to MB (mVTE/MB=0.39; tVTE/MB=0.10). At the reference tradeoff value, the AC/timing combination with the highest probability of having the best risk-benefit profile was postop xim analyzed by both mVTE and tVTE (99 and 58%, respectively). After excluding xim the AC/timing combination of choice was postop LMWH if analyzed by mVTE (60%) or preop LMWH if analyzed by tVTE (59%). When all AC were pooled those administered postop had the highest probability of having the best risk-benefit profile analyzed by mVTE (48%) and the choice was indifferent between preop (45%) and postop (40%) if analyzed by tVTE. After excluding xim from the pooled analysis the choice was indifferent between preop (40%) and postop (35%) if analyzed by mVTE and if analyzed by tVTE the choice was preop (55%) followed by postop (27%). Our results suggest that: postop administration of AC proph has the best risk-benefit profile; the results are influenced by the event defining benefit (mVTE or tVTE); in some analyses preop administration was best, and; periop administration always had the worst risk-benefit profile. We conclude that periop AC proph after OS should not be used.

Background Previous trials have evaluated the effects of aerobic training alone and of resistance training alone on glycemic control in type 2 diabetes, as assessed by hemoglobin A1c values. However, none could assess incremental effects of combined aerobic and resistance training compared with either type of exercise alone. Objective To determine the effects of aerobic training alone, resistance training alone, and combined exercise training on hemoglobin A1c values in patients with type 2 diabetes. Design Randomized, controlled trial. Setting 8 community-based facilities. Patients 251 adults age 39 to 70 years with type 2 diabetes. A negative result on a stress test or clearance by a cardiologist, and adherence to exercise during a 4-week run-in period, were required before randomization. Interventions Aerobic training, resistance training, or both types of exercise (combined exercise training). A sedentary control group was included. Exercise training was performed 3 times weekly for 22 weeks (weeks 5 to 26 of the study). Measurements The primary outcome was the change in hemoglobin A1c value at 6 months. Secondary outcomes were changes in body composition, plasma lipid values, and blood pressure. Results The absolute change in the hemoglobin A1c value in the combined exercise training group compared with the control group was -0.51 percentage point (95% CI, -0.87 to -0.14) in the aerobic training group and -0.38 percentage point (CI, -0.72 to -0.22) in the resistance training group. Combined exercise training resulted in an additional change in the hemoglobin A1c value of -0.46 percentage point (CI, -0.83 to -0.09) compared with aerobic training alone and -0.59 percentage point (CI, -0.95 to -0.23) compared with resistance training alone. Changes in blood pressure and lipid values did not statistically significantly differ among groups. Adverse events were more common in the exercise groups. Limitations The generalizability of the results to patients who are less adherent to exercise programs is uncertain. The participants were not blinded, and the total duration of exercise was greater in the combined exercise training group than in the aerobic and resistance training groups. Conclusion Either aerobic or resistance training alone improves glycemic control in type 2 diabetes, but the improvements are greatest with combined aerobic and resistance training. ClinicalTrials.gov registration number: NCT00195884.

9000 Background: Wage losses after breast cancer may result in considerable financial burden. More women now participate in the workforce and breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated the burden from wage losses and determinants among Canadian women in the first 12 months after newly diagnosed non-metastatic breast cancer. Methods: This prospective cohort study was conducted among 800 women from 8 hospitals (participation 83%) of whom 459 were working at diagnosis. For these latter women, information on potential determinants of wage losses, work absences, compensation received and perception of financial situation was collected by 3 telephone interviews over the year. Information on medical characteristics came from medical files. The main outcome was the relative loss, namely wages lost divided by annual wages the woman would have earned had she not been absent from work. ANOVA was used to identify determinants. Results: The median relative loss in the first year after diagnosis for the 403 women reporting an absence or reduced work hours was 19% or $5,502 (Can dollars). Multivariate analysis showed that the mean relative loss was 13% for women who reported that breast cancer was not at all costly compared to 22%, 33% and 38% among women who said that breast cancer was a bit, quite or very costly, respectively (ptrend No significant financial relationships to disclose.

Major VTE is the most frequent complication of OS. Current recommendations are to administer prophylaxis with an anticoagulant agent for at least 7–10 days. Numerous studies have evaluated different agents for this purpose. Although the most recent studies are usually methodologically sound, several studies have been hampered by inappropriate designs and insufficient sample sizes. In order to help with the design of future trials we conducted a systematic review of randomized trials evaluating short-term (< 15 days) administration of anticoagulants for VTE prophylaxis in OS and performed a MA of simple proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), and major bleeding episodes (as defined by the authors and defined using a definition similar to the one proposed by the International Society on Thrombosis and Haemostasis-ISTH). We included randomized trials comparing different drugs for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, tomographic angiography, or ventilation perfusion lung scan). Heterogeneity of proportions was evaluated using a chi ² test and pooled estimates of proportions were obtained using a fixed or a random effects model as appropriate. In the latter the weights were estimated as proposed by Laird and Mosteller. We retrieved 55 studies (135 research arms) which enrolled 42,131 patients. The percentage and variance of major and total VTE and major bleeding are shown in table 1. The total number of events and the number of evaluable patients are shown in table 2. We found differences in the percentage of clinical outcomes associated with the use of different agents for VTE prophylaxis after OS, however, because of the analytical strategy used no estimation of odds or risk reduction can be derived from this data. We believe that these estimates will be of help for the design of future studies.

665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the results of preliminary research (Grunfeld, BMJ 1996;313:665), we hypothesized that routine follow-up in primary care is a safe and acceptable alternative to follow-up in specialist care. Methods: Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer center according to usual practice (CC arm) or follow-up from their family physician (FP arm). Patients in the FP arm were referred back to the cancer center if diagnosed with recurrence or a new primary cancer. The primary outcome was a comparison of the rate of ‘serious clinical events’ (SCE) defined as any one of the following: spinal cord compression, pathological fractures, hypercalcaemia, uncontrolled local recurrence, brachial plexopathy, or poor functional status (Karnofs...

© 2012 Lazo-Langner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery. Methods. Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding. Results: The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement. Conclusions: Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance. During the conduction of this work Dr. Alejandro Lazo-Langner was supported by a Graduate Scholarship from Consejo Nacional de Ciencia y Tecnología (CONACyT), México, an International Fellowship awarded by the University of Ottawa and by Program Grant PRG 5513 of the Heart and Stroke Foundation of Ontario. Dr. Marc A. Rodger is supported by a Career Scientist Research award from the Heart and Stroke Foundation of Ontario. Dr. Philip S. Wells is supported by the Canada Research Chairs Program.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The prevalence of physician-diagnosed-asthma has risen over the past three decades and misdiagnosis of asthma is potentially common. Objective: to determine whether a secondary-screening-program to establish a correct diagnosis of asthma in those who report a physician diagnosis of asthma is cost effective.Method: Randomly selected physician-diagnosed-asthmatic subjects from 8 Canadian cities were studied with an extensive diagnostic algorithm to rule-in, or rule-out, a correct diagnosis of asthma. Subjects in whom the diagnosis of asthma was excluded were followed up for 6-months and data on asthma medications and heath care utilization was obtained. Economic analysis was performed to estimate the incremental lifetime costs associated with secondary screening of previously diagnosed asthmatic subjects. Analysis was from the perspective of the Canadian healthcare system and is reported in Canadian dollars.Results: Of 540 randomly selected patients with physician diagnosed asthma 150 (28%; 95%CI 19-37%) did not have asthma when objectively studied. 71% of these misdiagnosed patients were on some asthma medications. Incorporating the incremental cost of secondary-screening for the diagnosis of asthma, we found that the average cost savings per 100 individuals screened was $35,141 (95%CI $4,588-$69,278).Conclusion: Cost savings primarily resulted from lifetime costs of medication use averted in those who had been misdiagnosed. This work was funded by the Canadian Institute of Health Research, Canada and the University Of Ottawa Division Of Respiratory Medicine.