Cost-effectiveness of a primary care intervention to treat obesity.

BACKGROUND: Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant. METHODS: We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (UC; quarterly visits with their primary care provider); Brief Lifestyle Counseling (BLC; quarterly provider visits plus monthly weight loss counseling visits) or Enhanced Brief Lifestyle Counseling (EBLC; all above interventions, plus choice of meal replacements or weight loss medication). A health-care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality-adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY. RESULTS: Weight losses after 2 years were 1.7, 2.9 and 4.6 kg for UC, BLC and EBLC, respectively (P=0.003 for comparison of EBLC vs UC). The incremental cost per kilogram-year lost was $292 for EBLC compared with UC (95% confidence interval (CI): $219-$437). The short-term incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short-term cost per kg with published estimates of longer-term cost per QALY suggested that the intervention could be cost-effective over the long term (≥ 10 years). CONCLUSIONS: A primary care intervention that includes monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity.

Direct medical cost of overweight and obesity in the USA: a quantitative systematic review.

To estimate per-person and aggregate direct medical costs of overweight and obesity and to examine the effect of study design factors. PubMed (1968-2009), EconLit (1969-2009) and Business Source Premier (1995-2009) were searched for original studies. Results were standardized to compute the incremental cost per overweight person and per obese person, and to compute the national aggregate cost. A total of 33 US studies met review criteria. Among the four highest-quality studies, the 2008 per-person direct medical cost of overweight was $266 and of obesity was $1723. The aggregate national cost of overweight and obesity combined was $113.9 billion. Study design factors that affected cost estimates included use of national samples vs. more selected populations, age groups examined, inclusion of all medical costs vs. obesity-related costs only, and body mass index cut-offs for defining overweight and obesity. Depending on the source of total national healthcare expenditures used, the direct medical cost of overweight and obesity combined is approximately 5.0% to 10% of US healthcare spending. Future studies should include nationally representative samples, evaluate adults of all ages, report all medical costs and use standard body mass index cut-offs.

Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study.

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed. For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region. SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400-123,500 USD). Estimates for Salm versus P (197,000 USD) and FP versus P (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFC versus P, the cost per QALY was 77,100 (46,200-241,700) USD compared to 24,200 (15,200-56,100) USD in Western Europe. Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.

Economic analysis of conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer.

We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.

A comparison of scoring weights for the EuroQol derived from patients and the general public.

OBJECTIVE: General health state classification systems, such as the EuroQol instrument, have been developed to improve the systematic measurement and comparability of health state preferences. In this paper we generate valuations for EuroQol health states using responses to this instrument's visual analogue scale made by patients enrolled in a randomized clinical trial evaluating tirilazad mesylate, a new drug used to treat subarachnoid haemorrhage. We then compare these valuations derived from patients with published valuations derived from responses made by a sample from the general public. METHODS: The data were derived from two sources: (1) responses to the EuroQol instrument from 649 patients 3 months after enrollment in the clinical trial, and (2) from a published study reporting a scoring rule for the EuroQol instrument that was based upon responses made by the general public. We used a linear regression model to develop an additive scoring rule. This rule enables direct valuation of all 243 EuroQol health states using patients' scores for their own health states elicited using a visual analogue scale. We then compared predicted scores generated using our scoring rule with predicted scores derived from a sample from the general public. RESULTS: The predicted scores derived using the additive scoring rules met convergent validity criteria and explained a substantial amount of the variation in visual analogue scale scores (R(2)=0.57). In the pairwise comparison of the predicted scores derived from the study sample with those derived from the general public, we found that the former set of scores were higher for 223 of the 243 states. Despite the low level of correspondence in the pairwise comparison, the overall correlation between the two sets of scores was 87%. CONCLUSIONS: The model presented in this paper demonstrated that scoring weights for the EuroQol instrument can be derived directly from patient responses from a clinical trial and that these weights can explain a substantial amount of variation in health valuations. Scoring weights based on patient responses are significantly higher than those derived from the general public. Further research is required to understand the source of these differences.

Quantifying stochastic uncertainty and presenting results of cost-effectiveness analyses.

In the last decade, major advances have been made in the statistical methods for quantifying uncertainty in stochastic cost-effectiveness studies. In this paper, we provide a guide to the literature in which we highlight the preferred methods for confidence interval estimation, new developments in the formulation of the cost-effectiveness problem, suggested ways for presenting results and the areas in which future research may develop. The overall approach taken is nontechnical, with an emphasis on graphical rather than algebraic presentation of methods.

Predicting 10-year care requirements for older people with suspected Alzheimer's disease.

OBJECTIVE: To describe the types and costs of care received for 10 years after the identification of an older person with suspected Alzheimer's disease (AD) by using data from 3254 patients with suspected AD who participated in the National Long Term Care Survey (NLTCS). METHODS: By using a Markov model derived using grade of membership techniques, the following were determined: survival probabilities at 10 years; years of survival during the 10 years; years in institutions; years with two or more impairments in basic activities of daily living; hours of paid and informal care while the older person lived in the community; and costs of paid community, institutional, and medical care. RESULTS: Greater degrees of cognitive impairment present when AD was identified were associated with reduced predicted probability of surviving 10 years, increased predicted number of years spent in institutions, increased hours of care required while affected individuals remained in the community, and increased costs of paid community, institutional, and medical care. Substantial differences between men and women were seen: severity-adjusted 10-year costs were almost two times higher for women with AD than for men ($75,000 compared with $44,000); according to sensitivity analysis, average 10-year costs might be as high as $109,000 for women and $67,000 for men. CONCLUSIONS: AD imposes a substantial burden on older persons. Interventions that slow the progression of the disease may therefore affect community survival as well as healthcare costs.

Determining an episode of care using claims data. Diabetic foot ulcer.

OBJECTIVE: Amid changes in the organization and financing of health care, health care decision makers are increasingly interested in episodes of care. We sought to determine an episode of care for diabetic foot ulcer using an administrative claims database. RESEARCH DESIGN AND METHODS: We used 1993-1995 claims data to assess resource utilization for privately insured patients with diabetic foot ulcers. Over a 26-week period, we determined the episode length by comparing differences in average daily charges and proportion of patients with charges before and after foot ulcer diagnosis. All 13 weeks before diagnosis were used to calculate baseline values. Significance was determined by CIs, which were calculated by a nonparametric bootstrap technique. Costs associated with the episode were also calculated. A sensitivity analysis using weeks with highest and lowest values as baseline was also conducted. RESULTS: Based on average daily charges, the episode of care for diabetic foot ulcer was 5 weeks. Using proportion of patients with charges, the episode was longer than 13 weeks. The cost for an episode of care ranged from $900 to $2,600. In the sensitivity analyses, episodes of care ranged from 1 to 13 weeks. CONCLUSIONS: Episodes of care can be defined by the period beginning with increased resource consumption and ending when resource consumption returns to baseline levels. With the growth of managed care and disease management programs, episode-of-care analysis may have an increasingly important role in health care provision and delivery.

Analytic approaches for the evaluation of costs.

Currently, economic evaluation of new medical therapies is conducted routinely. Development of an analysis plan before performance of the analysis is a first step in the analysis of data from such evaluations. Univariate analysis of costs can be performed with both parametric and nonparametric tests. Potential multivariable analyses include ordinary least squares regression, nonparametric hazard models, parametric failure time models, Cox semiparametric regression, and joint distributions of survival and cost. In addition to developing point estimates for economic outcomes, 95% confidence intervals for cost-effectiveness ratios should be developed to evaluate the level of uncertainty that surrounds these estimates. Sensitivity analysis should be used to address other sources of uncertainty.

A comparison of preference assessment instruments used in a clinical trial: responses to the visual analog scale from the EuroQol EQ-5D and the Health Utilities Index.

OBJECTIVES: To compare preference assessments that were made by using the EuroQol EQ-5D and the Health Utilities Index Mark II. SUBJECTS: 561 patients in a randomized trial of tirilazad mesylate for aneurysmal subarachnoid hemorrhage. MEASURES: Three preference assessments (a value score for the EuroQol instrument and value and utility scores for the Health Utilities Index) made three months after randomization. The averages for each of the three scores, stratified by clinical outcomes and attributes of the Health Utilities Index health status classification system, were compared. To evaluate potential sources of difference between the instruments, the authors estimated two alternative Health Utilities Index scoring rules that were based on patient responses to the EuroQol instrument. RESULTS: Patients' ratings of their current health made by using the 100-point visual analog scale from the EuroQol instrument were more similar to the utility scores for the Health Utilities Index than they were to the value scores for the Health Utilities Index. The biggest differences between the visual analog scores for the EuroQol instrument and the utility scores for the Health Utilities index were seen at higher levels of functioning. CONCLUSION: For states representing higher levels of functioning, differences were seen between patients' self-ratings obtained by using the EuroQol instrument and the patients' utility scores on the Health Utilities Index; for states representing lower levels of functioning, substantial agreement was observed between these two scores. Differences observed at the higher levels of functioning suggest that further research is needed to determine whether the Health Utility Index's assignment of a score of 1.0 to the reference state representing being healthy is appropriate.

Clinical economics in clinical trials: the measurement of cost and outcomes in the assessment of clinical services through clinical trials.

As the population ages and more expensive high-technology services become available, health care costs continue to spiral upward. Because the financial resources for health care are limited, economic analysis can help to evaluate expenditures and set priorities. Economic analysis of medical technology or medical care evaluates a medical service by comparing its dollar cost with its dollar benefit (cost-benefit), by measuring its dollar cost in relation to its outcomes (cost-effectiveness) as well as in relation to its utility or quality-adjusted outcomes (cost-utility), or simply by tabulating the costs involved (cost-identification). Direct costs are generated as services are provided. In addition, patients' productivity is affected, and these costs can be considered, especially in determining the benefit of a service that decreases morbidity or mortality. Intangible costs are those of pain, suffering, and grief. The point of view, or perspective, of the study determines the costs and benefits that will be measured in the analysis. Sensitivity analysis, which can evaluate the stability of the conclusions to the data used, is an important assessment within economic analysis. Economic analysis of new pharmaceutical therapies is increasingly being incorporated into clinical trials. Although there are some limitations of pharmacoeconomic information in clinical studies of drug safety and efficacy, these trials are often the only opportunity for economic data collection before adoption and reimbursement decisions are made. Validation after the drug has been introduced should complement economic information developed from clinical trials.

Clinical and economic impact of a combination Haemophilus influenzae and Hepatitis B vaccine: estimating cost-effectiveness using decision analysis.

BACKGROUND: Compliance with hepatitis B virus (HBV) vaccine remains suboptimal, despite a recommendation by the Advisory Committee on Immunization Practices of the US Public Health Service that all newborns be vaccinated. Although a combined HBV-Haemophilus influenzae type b (Hib) vaccine may improve acceptance of the HBV vaccine, the clinical and economic consequences of this intervention are uncertain. OBJECTIVES: To compare the health impact and cost-effectiveness of the following 2 immunization strategies: current practice of administering HBV vaccine separately (75% compliance) and Hib vaccine alone or as part of a multivalent vaccine (95% compliance); and strategy of delivering a combined HBV-Hib vaccine (95% compliance). DESIGN: A Markov model simulated the natural history of acute and chronic HBV and Hib disease in a cohort of US newborns. Clinical and economic variables were obtained from published reports. RESULTS: The Hib-related outcomes were the same in both strategies, because the efficacy and compliance with Hib vaccine were assumed to be equivalent in both. A 53% reduction in the number of cases of HBV infection with the combination strategy (n = 8541) was estimated when compared with current practice (n = 18 044), along with 205 fewer HBV-related deaths per 1 million infants. Immunization costs of the combination strategy were $11.5 million higher than for current practice ($108.4 million compared with $96.9 million), whereas the cost of HBV-related disease was $4.0 million lower than in current practice. The incremental cost-effectiveness ratio for the combination strategy was $17700 per year of life saved. CONCLUSION: An HBV-Hib vaccine in US infants yields substantial benefits, with a cost-effectiveness ratio that is lower than that of many commonly used medical interventions.

Estimating country-specific cost-effectiveness from multinational clinical trials.

Because costs and outcomes of medical treatments may vary from country to country in important ways, decision makers are increasingly interested in having data based on their own country's health care situations. This paper proposes methods for estimating country-specific cost-effectiveness ratios from data available from multinational clinical trials. It examines how clinical and economic outcomes interact when estimating treatment effects on cost and proposes empirical methods for capturing these interactions and incorporating them when making country-specific estimates. We use data from a multinational phase III trial of tirilazad mesylate for the treatment of subarachnoid haemorrhage to illustrate these methods. Our findings suggest that it is possible for meaningful country-by-country differences to be found in such trial data. These differences can be useful in informing reimbursement, utilization, and other decisions taken at the country level.

Empirical criteria for the selection of quality-of-life instruments for the evaluation of peripheral blood progenitor cell transplantation.

We propose a method for selecting quality-of-life instruments for use in phase III trials using the convergent validity of patient responses collected in phase I and II clinical trials. Two generic and two disease-specific instruments were administered to patients with breast cancer undergoing peripheral blood progenitor cell mobilization and transplantation. They included the visual analog scale from the EuroQoL EQ5D instrument, the SF-36, the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30, and the Functional Assessment of Cancer Therapy instrument. No single instrument was found to have superior convergent validity in all domains, but the EORTC-QLQ-C30 seemed to perform better than the SF-36.

Prospective economic evaluation accompanying a trial of GM-CSF/IL-3 in patients undergoing autologous bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. IL-3 BMT Study Team.

Our objective was to assess the economic impact of a new cytokine therapy that was being compared to standard therapy as supportive care in patients receiving autologous bone marrow transplantation for treatment of lymphoma. We performed an economic study accompanying a multicenter, randomized, controlled clinical trial in academic medical centers. One hundred and fifteen patients consented to participate in a parallel economic study of a randomized controlled trial of sequential IL-3 followed by GM-CSF vs GM-CSF alone after autologous bone marrow transplantation. We measured costs and quality-adjusted survival over a 13-month follow-up period. For the 13-month study period, the total cost estimates were $79892 (95% CI $69343 to $90544) for patients receiving GM-CSF alone and $89651 (95% CI $79769 to $102114) for patients receiving IL-3/GM-CSF. The difference was not statistically significant. During the 13-month study period, the total number of quality-adjusted life-months in the GM-CSF arm was 6.67 (95% CI 5.75 to 7.56) months, while the total number of quality-adjusted life-months in the IL-3 arm was 6.26 (95% CI 5.34 to 7.15) months. The difference in quality-adjusted life-months between the two treatment arms was not statistically significant. We conclude that economic analysis of a phase III clinical trial of IL-3/GM-CSF compared with GM-CSF alone showed no significant effect of IL-3 on the costs of care for patients undergoing bone marrow transplantation for a period of up to 13 months after the procedure. This study demonstrates the feasibility of prospective economic evaluation within phase III trials of new cancer therapies. Data from this type of economic protocol could be used to help physicians, patients and managed care organizations understand the effect of new treatments from both a clinical and an economic perspective.

Comparison of the use of medical resources and outcomes in the treatment of aneurysmal subarachnoid hemorrhage between Canada and the United States.

OBJECTIVE: Using data from a randomized trial of tirilazad mesylate, we assessed the differences between Canada and the United States in the use of medical resources and outcomes in the treatment of aneurysmal subarachnoid hemorrhage during the first 90 days after admission to the hospital. METHODS: Of the 877 patients for whom economic data were available, 194 were enrolled in Canada and 683 were enrolled in the United States. The differences between the countries in patient characteristics, use of medical resources, and outcomes were analyzed by comparing means and the 95% confidence intervals (CIs) around the differences in means. These differences also were predicted with use of multivariable regression analysis. RESULTS: The average hospital stay was 4.2 days longer (95% CI, 1.3 to 7.1 days) in Canada, but most of the extra stay was among patients admitted to the study in poor neurological condition. In general, however, hospital stays in Canada were substantially less intensive. Patients treated in Canada spent 3.7 fewer days (95% CI, 1.2 to 6.1 days) in nursing homes and rehabilitation centers than did patients in the United States. No statistically significant differences were seen for Glasgow Outcome Scale score, death, and occurrence of vasospasm. CONCLUSIONS: For patients admitted to the study in good neurological condition, the apparent difference in length of stay between Canada and the United States was caused by a shift in the sites of formal care rather than to the length of this care. For those admitted in poor neurological condition, both the length and sites of care differed between the two countries. No significant difference in outcomes appeared to justify these differences in the use of medical resources.

The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction.

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (> or = 140 mm Hg) or diastolic (> or = 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.

Confidence intervals for cost-effectiveness ratios: a comparison of four methods.

We evaluated four methods for computing confidence intervals for cost-effectiveness ratios developed from randomized controlled trials: the box method, the Taylor series method, the nonparametric bootstrap method and the Fieller theorem method. We performed a Monte Carlo experiment to compare these methods. We investigated the relative performance of each method and assessed whether or not it was affected by differing distributions of costs (normal and log normal) and effects (10% absolute difference in mortality resulting from mortality rates of 25% versus 15% in the two groups as well as from mortality rates of 55% versus 45%) or by differing levels of correlation between the costs and effects (correlations of -0.50, -0.25, 0.0, 0.25 and 0.50). The principal criterion used to evaluate the performance of the methods was the probability of miscoverage. Symmetrical miscoverage of the intervals was used as a secondary criterion for evaluating the four methods. Overall probabilities of miscoverage for the nonparametric bootstrap method and the Fieller theorem method were more accurate than those for the other the methods. The Taylor series method had confidence intervals that asymmetrically underestimated the upper limit of the interval. Confidence intervals for cost-effectiveness ratios resulting from the nonparametric bootstrap method and the Fieller theorem method were more dependably accurate than those estimated using the Taylor series or box methods. Routine reporting of these intervals will allow individuals using cost-effectiveness ratios to make clinical and policy judgments to better identify when an intervention is a good value for its cost.

Routine portable chest radiographs in the medical intensive care unit: effects and costs.

OBJECTIVE: To determine the effects and net costs of routine chest radiographs in a medical intensive care unit (ICU). DESIGN: A prospective, cohort study. A survey of experts in critical care and pulmonary diseases was undertaken to assess the effect of routine radiographs on patient management. SETTING: Medical ICU of a university hospital. PATIENTS: Eighty randomly selected patients admitted to a medical ICU. Two hundred fourteen experts were surveyed; 118 (55%)/214 responded. MEASUREMENTS AND MAIN RESULTS: Daily interviews with medical ICU clinicians were conducted to assess the radiographic findings in the routine radiographs and actions taken based on these findings. Experts evaluated the findings, their importance, the actions taken, and the probability of complications if the actions had not been taken at that time. Experts also predicted increases in length of stay associated with these complications. Presence of radiographic findings, changes in management because of the findings, net costs of routine chest radiographs, cost per finding that prompted an action, and expected changes in length of stay resulting from the actions were also assessed. Seventy-two (33%) of 221 routine radiographs (95% confidence interval: 25% to 39%) had findings, of which 44 (61%) were judged important, and 18 (8%, 95% confidence interval: 5% to 12%) prompted actions. Experts predicted that each action averted, on average, 2.1 +/- 1.7 days (SD) in the medical ICU. Mean savings per routine radiograph was $98. Net savings from routine chest radiographs remained after sensitivity analysis for expected change in length of stay, percentage of patients with routine radiographs, and percentage of routine radiographs that produce changes in management. CONCLUSION: The policy of obtaining routine chest radiographs in the medical ICU is effective and results in net savings.