Health Preference Research in Europe: A Review of Its Use in Marketing Authorization, Reimbursement, and Pricing Decisions-Report of the ISPOR Stated Preference Research Special Interest Group.

OBJECTIVE: This study examines European decision makers' consideration and use of quantitative preference data. METHODS: The study reviewed quantitative preference data usage in 31 European countries to support marketing authorization, reimbursement, or pricing decisions. Use was defined as: agency guidance on preference data use, sponsor submission of preference data, or decision-maker collection of preference data. The data could be collected from any stakeholder using any method that generated quantitative estimates of preferences. Data were collected through: (1) documentary evidence identified through a literature and regulatory websites review, and via key opinion leader outreach; and (2) a survey of staff working for agencies that support or make healthcare technology decisions. RESULTS: Preference data utilization was identified in 22 countries and at a European level. The most prevalent use (19 countries) was citizen preferences, collected using time-trade off or standard gamble methods to inform health state utility estimation. Preference data was also used to: (1) value other impact on patients, (2) incorporate non-health factors into reimbursement decisions, and (3) estimate opportunity cost. Pilot projects were identified (6 countries and at a European level), with a focus on multi-criteria decision analysis methods and choice-based methods to elicit patient preferences. CONCLUSION: While quantitative preference data support reimbursement and pricing decisions in most European countries, there was no utilization evidence in European-level marketing authorization decisions. While there are commonalities, a diversity of usage was identified between jurisdictions. Pilots suggest the potential for greater use of preference data, and for alignment between decision makers.

Multiple criteria decision analysis for health technology assessment.

OBJECTIVES: Multicriteria decision analysis (MCDA) has been suggested by some researchers as a method to capture the benefits beyond quality adjusted life-years in a transparent and consistent manner. The objectives of this article were to analyze the possible application of MCDA approaches in health technology assessment and to describe their relative advantages and disadvantages. METHODS: This article begins with an introduction to the most common types of MCDA models and a critical review of state-of-the-art methods for incorporating multiple criteria in health technology assessment. An overview of MCDA is provided and is compared against the current UK National Institute for Health and Clinical Excellence health technology appraisal process. A generic MCDA modeling approach is described, and the different MCDA modeling approaches are applied to a hypothetical case study. RESULTS: A comparison of the different MCDA approaches is provided, and the generic issues that need consideration before the application of MCDA in health technology assessment are examined. CONCLUSIONS: There are general practical issues that might arise from using an MCDA approach, and it is suggested that appropriate care be taken to ensure the success of MCDA techniques in the appraisal process.

Estimating the health benefits and costs associated with ezetimibe coadministered with statin therapy compared with higher dose statin monotherapy in patients with established cardiovascular disease: results of a Markov model for UK costs using data registries.

BACKGROUND: Ezetimibe has been reported to improve lipid control in patients with established cardiovascular disease (CVD). OBJECTIVE: The aim of this study was to estimate the potential long-term impact on health status of prescribing ezetimibe in combination with statin therapy in patients with established CVD and evaluate its cost-effectiveness in a health economic model. METHODS: A Markov model was used to compare ezetimibe and statin combination therapy with statin monotherapy. A published relationship linking changes in low-density lipoprotein cholesterol and cardiovascular events was used to estimate the cardiovascular events avoided through lipid-lowering therapies. The model was populated using results of extensive literature searches and a meta-analysis of clinical evidence. An adjustment was applied to model second-line lipid-lowering benefits. Conservative assumptions were used to extend the patient pathway beyond the clinical evidence. The analysis took the perspective of the UK Department of Health; therefore, only direct costs were included. Costs were calculated as year-2006 British pounds. RESULTS: For a cohort of 1,000 hypothetical male patients aged 55 years, ezetimibe coadministered with current statin therapy was estimated to prevent a mean of 43 nonfatal myocardial infarctions, 7 nonfatal strokes, and 26 cardiovascular deaths over a lifetime, compared with doubling the current statin dose. The events avoided would provide a mean of 134 additional quality-adjusted life-years (QALYs). With a mean incremental cost of pound 3,693,000, the lifetime discounted cost per QALY gained would be pound 27,475 (95% CI, pound 27,331- pound 27,620) and would rise to pound 32,000 for men aged 75 years. CONCLUSIONS: The results suggest that, in some instances, ezetimibe coadministration may be cost-effective compared with statin monotherapy, but there are several limitations with this model. The economic effects of ezetimibe must be revisited when long-term effectiveness and safety data become available.

Cost effectiveness of ezetimibe in patients with cardiovascular disease and statin intolerance or contraindications: a Markov model.

OBJECTIVE: To evaluate the cost effectiveness of long-term ezetimibe monotherapy in patients with established cardiovascular disease (CVD) who do not tolerate statins or in whom they are contraindicated. METHODS: A Markov model was used to estimate the potential costs and benefits associated with ezetimibe monotherapy compared with no treatment. The benefits associated with ezetimibe treatment were informed by a systematic review of clinical evidence and a published relationship linking changes in low-density lipoprotein cholesterol (LDL-C) levels to cardiovascular events. RESULTS: In the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid levels were used as indicators of clinical outcomes. A meta-analysis of seven placebo-controlled trials included in the review showed that ezetimibe was associated with a statistically significant mean reduction (from baseline to endpoint) in LDL-C of 18.56% (95% CI -19.68, -17.44; p < 0.00001) compared with placebo. Using 10,000 Monte Carlo simulations, it is estimated that ezetimibe monotherapy would prevent an average of 49 nonfatal myocardial infarctions, 11 nonfatal strokes, and 37 cardiovascular deaths in a cohort of 1,000 patients aged 55 years with a baseline LDL-C concentration of 4.0 mmol/L. Events avoided provide an additional 211 quality-adjusted life-years (QALYs) over the 45 years modeled. With a mean incremental cost of pound 4,861,000 (year 2006 value), the discounted cost per QALY is pound 23,026 (Jackknife CI 22 979, 23 074). The model is reasonably robust to variations in key parameters. Incremental cost-effectiveness ratios fall below pound 20,000 per QALY for cohorts with baseline LDL-C values >4.5 mmol/L. CONCLUSION: Ezetimibe monotherapy compared with no treatment is a cost-effective alternative for individuals with a history of CVD and high LDL-C levels, who do not tolerate statins or in whom they are contraindicated.

[Incidence and risk factors for bacteremia on pediatric patients with burns in a specialized care center in Mexico]. / Incidencia y factores de riesgo para bacteriemia en pacientes pediátricos con quemaduras en un Centro de Atención Especializado en México.

BACKGROUND: Bacteremia events are frequent cause of mortality in burn patients and may originate from infected wounds, by bacterial translocation of endogenous microorganisms, from invasive devices or contaminated intravenous solutions. OBJECTIVE: To quantify the incidence of bacteremia in pediatric patients with burns and to identify risk factors. MATERIAL AND METHODS: A prospective cohort study was performed in pediatric patients with burns of Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". Bacteremia was diagnosed by blood cultures in patients with clinical manifestations of sepsis. Risk factors were investigated by multivariate analysis with Cox regression. RESULTS: Were included in the cohort 260 patients, median age 3 years. The incidence of bacteremia was 9.6 events per 1,000 days patient. The most frequently isolated bacteria were Enterobacteriaceae (41.9%), Staphylococcus aureus (22.6%) and Pseudomonas aeruginosa (22.6%). Factors associated with bacteremia were: bums ≥ 20% TBSA (HR 11.06; 95% CI 4.8-25.4), deep second degree bums or higher (HR 6.9; 95% CI 2.0-23.3) and have had two or less debridement (HR 26.4; 95% CI 8.0-87.7). CONCLUSIONS: Patients with more extensive and deep burns with fewer debridement are at increased risk of bacteremia.

Cost-effectiveness of a cardiovascular disease primary prevention programme in a primary health care setting. Results of the Polish part of the EUROACTION project.

BACKGROUND: Well designed cardiovascular disease (CVD) prevention programmes appear to be generally applicable and effective in reducing exposure to risk factors and the incidence of disease. However, introducing them broadly into clinical practice would have a significant impact on the healthcare budget, and requires careful consideration. AIM: The purpose of this health economic analysis was to assess the potential cost-effectiveness of the model nurse-led, comprehensive CVD primary prevention programme which was prepared and introduced in the EUROACTION project, in high-risk patients in Poland. METHODS: A Markov model was developed to assess the long-term costs of preventive intervention. The health states modelled were: event-free (all patients at the beginning of observation), stable angina first year, acute myocardial infarction, stable angina subsequent year, myocardial infarction subsequent year, CVD death, and other causes of death. Health benefits from the reduction in risk factors were estimated based on Framingham risk function assuming the probability of defined health states according to British registers. The time horizon of the analysis was ten years, and one Markov cycle length was one year. The analysis was prepared from the healthcare payer's perspective. A willingness to pay threshold of three gross domestic product (GDP) per capita / quality-adjusted life years (QALY) was used. Univariate sensitivity analysis was conducted. Results were presented as an incremental cost-effectiveness ratio (ICER) expressed as an incremental cost per QALY. RESULTS: In Poland, EUROACTION intervention resulted mainly in reductions in the prevalence of smoking (by 14%) and high blood pressure (by 7%). Intervention on other risk factors, including blood lipids, was found to be less effective. Estimated ICERs were 19,524 PLN for men and 82,262 PLN for women. The programme was even more cost-effective in smokers i.e. estimated ICERs were 12,377 PLN in men and 53,471 PLN in women. The results were most sensitive to variations in health states utilities and cost value range as well as the duration of treatment effect. CONCLUSIONS: The model nurse-led, comprehensive CVD primary prevention programme developed in the EUROACTION project appears to be potentially highly cost-effective for high-risk male patients in Poland (below 1 GDP per capita per QALY). For women, the cost-effectiveness was less but still below the acceptable threshold (below three GDP per capita per QALY), although the sensitivity analysis showed that results were a subject of some uncertainty.

Incidencia y factores de riesgo para bacteriemia en pacientes pediátricos con quemaduras en un Centro de Atención Especializado en México / Incidence and risk factors for bacteremia on pediatric patients with burns in a specialized care center in Mexico

Background: Bacteremia events are frequent cause of mortality in burn patients and may originate from infected wounds, by bacterial translocation of endogenous microorganisms, from invasive devices or contaminated intravenous solutions. Objective: To quantify the incidence of bacteremia in pediatric patients with burns and to identify risk factors. Material and Methods: A prospective cohort study was performed in pediatric patients with burns of Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". Bacteremia was diagnosed by blood cultures in patients with clinical manifestations of sepsis. Risk factors were investigated by multivariate analysis with Cox regression. Results: Were included in the cohort 260 patients, median age 3 years. The incidence of bacteremia was 9.6 events per 1,000 days patient. The most frequently isolated bacteria were Enterobacteriaceae (41.9%), Staphylococcus aureus (22.6%) and Pseudomonas aeruginosa (22.6%). Factors associated with bacteremia were: bums ≥ 20% TBSA (HR 11.06; 95% CI 4.8-25.4), deep second degree bums or higher (HR 6.9; 95% CI 2.0-23.3) and have had two or less debridement (HR 26.4; 95% CI 8.0-87.7). Conclusions: Patients with more extensive and deep burns with fewer debridement are at increased risk of bacteremia.

Introducción: Los eventos de bacteriemia son causa frecuente de mortalidad en pacientes con quemaduras y pueden originarse en heridas infectadas, por translocación bacteriana de microorganismos endógenos, por dispositivos invasores o por soluciones intravenosas contaminadas. Objetivo: Cuantificar la incidencia de bacteriemia en pacientes pediátricos con quemaduras e identificar los factores de riesgo. Material y Métodos: Estudio de cohorte prospectivo, en población pediátrica con quemaduras del Hospital Civil de Guadalajara "Dr. Juan I. Menchaca". En pacientes con manifestaciones clínicas de sepsis se diagnosticó bacteriemia mediante cultivos de sangre. Se indagaron factores de riesgo con análisis multivariado con regresión de Cox. Resultados: Se incluyeron en la cohorte 260 pacientes, mediana de edad 3 años. La incidencia de bacteriemia fue de 9,6 eventos por 1.000 días paciente. Las bacterias más frecuentes aisladas fueron enterobacterias (41,9%), Staphylococcus aureus (22,6%) y Pseudomonas aeruginosa (22,6%). Los factores asociados a bacteriemia fueron: quemaduras ≥ 20% de superficie corporal quemada (HR 11,06; IC 95% 4,8-25,4), quemaduras de segundo grado profundo o mayores (HR 6,9; IC 95% 2,0-23,3) y haber tenido dos o menos desbridamientos (HR 26,4; IC 95% 8,0-87,7). Conclusiones: Pacientes con quemaduras más extensas y profundas, con menor número de desbridamientos presentan mayor riesgo de bacteriemia.