Ignoring study design heterogeneity in meta-analyses.
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Atrial Fibrillation↗
Biomedical subjects
Krista F Huybrechts
Publications and source records attributed to Krista F Huybrechts.
Budgetary impact of treating acute bipolar mania in hospitalized patients with quetiapine: an economic analysis of clinical trials.
OBJECTIVE: To present a tool that allows estimation of the budget impact of treatments for acute mania in bipolar I disorder from a US healthcare payer perspective. METHODS: Using discrete event simulation, the course of individuals is simulated beginning with hospitalization. Discharge depends on symptom level measured by the Young Mania Rating Scale (YMRS). The treatment effect is determined using time-dependent regression equations derived from trial data, and decision rules obtained from clinical experts. Outcomes include: time to response and symptom resolution; proportion of subjects reaching each outcome; number of adverse events. Costs were obtained from hospital discharge databases, the National Medicare Physician Fee Schedule and RedBook. Different scenarios are examined, each describing the proportion of subjects on the various treatments (lithium, divalproex sodium, olanzapine, risperidone, and quetiapine--monotherapy and in combination with lithium). Analyses are intention-to-treat over 100 days, corresponding to follow-up in mania trials. Despite its flexibility and structural adaptability, the model has some important limitations related to the characteristics of the clinical trials. These include focus on inpatient management of acute mania, use of the YMRS as the model driver, polypharmacy restricted to two-drug regimens, no explicit consideration of titration and dose changes, and relatively short time horizon. RESULTS: Scenarios with a greater proportion of quetiapine users (5% vs. 40% and 100%) result in a smaller impact on the healthcare budget (6912, 6277, and 5525 dollars per patient, respectively) and improvements in patient outcomes (e.g., 43%, 47%, and 54% responding at day 21; 74%, 77%, and 80% remitting by day 84). Sensitivity analyses showed that the budget impact is influenced by drug prices, discharge criteria and side-effect management. CONCLUSION: Results suggest that increased use of quetiapine for bipolar mania in the US is economically justified and improves health outcomes. In addition, this model illustrates that discrete event simulation is a useful and versatile tool for budget impact analyses.
Antipsychotic Agents↗
Assessment of compliance with osteoporosis treatment and its consequences in a managed care population.
OBJECTIVE: To evaluate non-compliance with osteoporosis medications as well as its implications for health and economic outcomes in actual practice. STUDY DESIGN: Data on demographics, prescription drug dispensing, physician services and hospitalizations were obtained from a US managed care database for women with osteoporosis who were dispensed an osteoporosis medication between 1997 and 2002. METHODS: Each subject's pattern of osteoporosis medication use was reconstructed using dispensing records. Subjects were considered compliant over a given period if their medication possession ratio (MPR) was >or=80% and gradients of compliance (<50% poor, 50-80% medium, 80-90% good, >90% excellent) were also examined. Using proportional hazards, the association between compliance over time and fracture rates was examined; Poisson regression was used for hospitalization and log-linear regression for medical costs. RESULTS: 38,120 women with osteoporosis were identified with a mean age of 66 years and an average follow-up of 1.7 years. Three quarters of them had an MPR below 80% when their entire follow-up was considered. Low compliance was associated with a 17% (95% CI 9-25%) increase in the fracture rate, adjusting for other known risk factors. Controlling for the specific drug regimen did not alter the association. Low compliance was also associated with a 37% (95% CI 32-43%) increase in the risk of all-cause hospitalization; and average monthly costs for all medical services combined were higher: 600 US dollars vs. 340 US dollars (P < 0.0001). Similar associations were observed when using the gradients of compliance. CONCLUSIONS: The desired goal of keeping patients with osteoporosis on chronic treatment is not being achieved adequately in actual practice and the potential social and economic implications of this behavior are substantial. Until compliance is improved, society will continue to fail in meeting an important public health goal.
Aged↗
Modeling the implications of changes in vascular calcification in patients on hemodialysis.
BACKGROUND: The Treat-to-Goal Study found that sevelamer slowed the progression of coronary calcification in patients on hemodialysis compared to calcium-based phosphate binders. To understand the implications of this effect for cardiovascular events, risk equations are needed. METHODS: Data on 179 patients on hemodialysis treated at one center in France included biochemical values during the year prior to study entry, patient characteristics, and cardiovascular events over an average of 4 years. As arterial calcification was evaluated ultrasonographically and quantified using a 0 to 4 score, an equation relating this to the electron-beam tomography (EBT)-based calcification score used in the trial was developed and applied to all patients. The estimated scores were then used in survival and Cox proportional hazards analyses of cardiovascular events in relation to the degree of calcification, controlling for other characteristics. RESULTS: Mean age at inclusion was 54 years, dialysis vintage 70 months, average follow-up 49 months; 32% suffered an event. The calcification score, diabetes, C-reactive protein (CRP), diastolic blood pressure, gender, smoking and hypertension are independent predictors of cardiovascular risk. The resulting equation indicates that, relative to a calcification score below 400, the risk of an initial event increases 44% for a score of 600, and more than doubles for a score of 1000. CONCLUSION: In the absence of long-term follow-up studies, these equations permit quantification of the expected long-term clinical consequences of the impact of various phosphate binders on vascular calcification. Together with resource use and cost information, these equations are key inputs for formal cost-effectiveness analyses.
Blood Pressure↗
The impact of compliance with osteoporosis therapy on fracture rates in actual practice.
BACKGROUND: Clinical trials have demonstrated that drug therapy can reduce osteoporosis-related fracture risk in women over 50 years of age. Noncompliance could considerably limit the effectiveness observed in actual practice, however. The objective of this study was therefore to estimate fracture risk in relation to compliance with osteoporosis medication in actual practice. METHODS: Demographic, prescription drug use, physician services, and hospitalization information for women with osteoporosis who were dispensed an osteoporosis medication between 1996 and 2001 was obtained from the Saskatchewan health data files. Compliance to treatment was defined as drug available to cover 80% of the time. Subsequent fractures were identified via hospitalizations or physician contacts with a relevant diagnostic or procedure code. The risk of fractures in relation to compliance was examined using a Cox proportional hazards model with time-dependent covariates. The impact of other patient characteristics, including age, having suffered a prior fracture, and prior use of osteoporosis medication and steroids, was also examined. RESULTS: 11,249 women suffering from osteoporosis were identified with a mean age at the time of the index prescription of 68.4 years and average follow-up of 2 years. The overall fracture rate was 4.5% per year. Patients who complied experienced a 16% lower fracture rate. This association was maintained within subgroups and after controlling for other patient characteristics that independently predict the fracture rate. CONCLUSION: These results indicate that improving compliance in actual practice may significantly decrease osteoporosis-related fracture risk.
Age Factors↗
Allocating funds for cardiovascular disease prevention in light of the NCEP ATP III guidelines.
BACKGROUND: Controversy persists about the most efficient allocation of healthcare funds for cardiovascular disease prevention. Previous economic analyses have generally focused on primary or secondary prevention as discrete categories. OBJECTIVES: To address the information required by decision-makers to distribute budgets optimally across an entire population at risk in view of recommendations promulgated by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). STUDY DESIGN AND METHODS: The Continuum of Risk Evaluation (CORE) model is an individual patient simulation of the occurrence of cardiovascular disease allowing for analyses over a broad range of risk. All events are tallied, costs are applied, and survival is modified accordingly. Disaggregated presentation of the results allows decision-makers to evaluate the budgetary implications and cost effectiveness of different strategies according to the risk at which treatment is initiated. This process is illustrated for the United States using information from the 1988-1994 National Health and Nutrition Examination Survey and pravastatin trials. RESULTS: Secondary prevention with pravastatin costs dollar 2900 per life-year gained for men and dollar 1100 per life-year gained for women. Lowering the treatment threshold to incorporate primary prevention yields cost-effectiveness ratios that remain below dollar 25 000 per undiscounted life-year gained until a 10-year cardiovascular disease risk of 14.4%. Cost savings are possible for very high-risk patients. CONCLUSIONS: The economic impact of an integrated approach to prevention of cardiovascular disease has not been thoroughly explored. CORE permits realistic analysis of policy decisions involving the entire continuum of risk rather than isolated consideration of specific disease stages, and thus provides a unique tool for assessing the full implications of treatment guidelines such as those of the NCEP ATP III.
Adult↗
Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review.
BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using chi2. RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis - despite its limitations - should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients.
Journal Article↗
Long term cost-of-illness in stroke: an international review.
An international review of the costs of stroke was conducted to explore data sources, and cost variables as well as to compare estimates of the annual aggregated cost (prevalence-based) and total per patient long-term cost (incidence-based) of care. Dutch, English, French, German, Italian and Spanish literature was searched using the keywords stroke, ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, cerebral infarction, cost(s), economics, and cost analysis. Criteria for study inclusion were: provides estimates of direct and/or indirect costs of stroke, published after 1989, methods described in adequate detail, and for studies of long-term costs, estimates based on a minimum 5 years of care following the event. Cost estimates are presented in original currencies and US dollars. Among studies representing Australia, New Zealand, Western Europe and North America, six prevalence studies reported total annual aggregated costs of US dollars 7,975 (1988 values) to US dollars 54,546 (1993 values) per patient; eight incidence-based studies reported total long-term per patient costs of US dollars 18,538 (1991 values) to US dollars 228,038 (1990 values). Identifiable factors underlying variation included: perspective employed, cost variables considered, and exclusion of comorbidities. Although lack of uniformity hampers inter-study comparisons, it is evident that stroke poses a significant economic burden. Consensus on standard cost variables and methods for projections of resource use and survival over time are clearly warranted.
Cost of Illness↗
Health and economic consequences of sevelamer use for hyperphosphatemia in patients on hemodialysis.
OBJECTIVES: The safety and efficacy of sevelamer hydrochloride in binding phosphate in patients with end-stage renal disease and its ability to attenuate the progression of cardiac calcification have been well documented but not the longer-term health and economic implications. Thus, a model of the predicted long-term consequences of sevelamer compared with calcium-based binders (acetate and carbonate) was developed. METHODS: Long-term cardiovascular implications of 1 year of treatment with phosphate binders in patients on hemodialysis are estimated based on the patient's demographics, comorbidities, and physiologic and renal parameters. The initial calcification score and expected changes over 1 year are derived using regression equations developed from the Treat-to-Goal study and translated to cardiovascular disease risk based on equations developed from a long-term cohort study. In this article, the implications of cardiovascular disease for life expectancy and medical costs are accounted for from a US payer perspective. RESULTS: The cardioprotective effect of sevelamer over 1 year is estimated to result in a 12% reduction in cardiovascular events compared with calcium acetate. In a population of 100 patients, the savings of 205,600 dollars accrued due to avoiding nine cardiovascular events with sevelamer, largely offset the increased binder costs, leading to a favorable cost-effectiveness ratio of about 2200 dollars per (discounted) life-year gained. CONCLUSIONS: Although both binders provide equivalent phosphate binding capacity, the results indicate that the advantage of 1 year of treatment with sevelamer in attenuating the progression of calcification has important clinical and economic consequences, suggesting that this provides good value for money.
Acetates↗