Estimating preference-based single index measures for dementia using DEMQOL and DEMQOL-Proxy.

OBJECTIVE: Although condition-specific measures are commonly used in dementia, they cannot be used in analyses of cost per quality-adjusted life-year because they do not incorporate preferences. We addressed this gap by estimating two preference-based single index measures: the DEMQOL-U from the self-report DEMQOL (mild-to-moderate dementia severity) and the DEMQOL-Proxy-U from the carer-report DEMQOL-Proxy (all levels of dementia severity). METHODS: We conducted valuation studies on 593 members of the general population (306 for the DEMQOL-U, 287 for the DEMQOL-Proxy-U) using the time trade-off elicitation technique. We then fitted a range of mean and individual-level multivariate regression models to the valuation data to derive preference weights for each measure. We applied the estimated weights to a large, clinically representative sample. RESULTS: Mean observed time trade-off values ranged from 0.18 to 0.95 for DEMQOL-U and from 0.33 to 0.96 for DEMQOL-Proxy-U. The best performing models for each measure were main effects models estimated using individual-level data. DEMQOL-Proxy-U had inconsistent but insignificant coefficient estimates for one dimension. Models were estimated to remove these inconsistencies. CONCLUSION: Preference-based single index measures from DEMQOL and DEMQOL-Proxy for use in economic evaluation will enable economic evaluation using quality-adjusted life-years to be undertaken for people across the full range of dementia severity. Future research will examine how the utilities from each measure can be used and combined to populate cost-effectiveness models.

Cost-effectiveness of Evolocumab in Patients With High Cardiovascular Risk in Spain.

PURPOSE: Our objective was to assess the cost-effectiveness of evolocumab in patients at high risk of cardiovascular (CV) events from the Spanish National Health System perspective. METHODS: A Markov model was used to assess the cost-effectiveness (incremental [∆] cost per ∆ quality-adjusted life-year [QALY]; or cost utility) of evolocumab plus standard of care (SoC; statins) versus SoC, assuming lifetime treatment. Cohorts with baseline LDL-C >100 mg/dL and familial hypercholesterolemia (FH) or CV event history (secondary prevention [SP]) were considered. Lifetime CV event rates were predicted either (1) using risk equations considering local risk factors (Spanish Familial Hypercholesterolemia Cohort Study) adjusted to reflect the increased risk of FH patients or (2) using CV event rates from local registries (Information System for the Development of Research in Primary Care) for SP patients. LDL-C relative reductions from evolocumab trials (Evolocumab 140 mg Q2W (bi-weekly) and 420 mg QM (monthly)) were converted into CV event reductions using rate ratios per millimole per liter (mmol/L; 38.67 mg/dL) from a meta-analysis of statin trials (Cholesterol Treatment Trialists' Collaboration). FINDINGS: Predicted 10-year/lifetime CV risks were 50%/95% (FH) and 62%/82% (SP) for SoC and 27%/83% (FH) and 44%/69% (SP) for evolocumab plus SoC. Predicted 10-year/lifetime major CV event risks were 42%/86% (FH) and 47%/67% (SP) for SoC and 21%/68% (FH) and 31%/52% (SP) for evolocumab plus SoC. Predicted per patient-year rates of non-fatal/fatal CV events were 2.2/0.8 (FH) and 1.1/0.6 (SP) for SoC and 1.2/0.6 (FH) and 0.7/0.5 (SP) for evolocumab plus SoC. Predicted CV event reductions per mmol/L were 17% (FH) and 15% (SP). Evolocumab treatment was associated with increased QALYs and costs compared with SoC (FH: ∆cost, €65,369; ∆QALY, 2.12; incremental cost-effectiveness ratio [ICER], €30,893; SP: ∆cost, €42,266; ∆QALY, 0.93; ICER, €45,340). IMPLICATIONS: Evolocumab plus to SoC may provide a cost-effective option for LDL-C lowering in FH and SP patients in Spain.

Dynamic microsimulation to model multiple outcomes in cohorts of critically ill patients.

BACKGROUND: Existing intensive care unit (ICU) prediction tools forecast single outcomes, (e.g., risk of death) and do not provide information on timing. OBJECTIVE: To build a model that predicts the temporal patterns of multiple outcomes, such as survival, organ dysfunction, and ICU length of stay, from the profile of organ dysfunction observed on admission. DESIGN: Dynamic microsimulation of a cohort of ICU patients. SETTING: 49Forty-nine ICUs in 11 countries. PATIENTS: One thousand four hundred and forty-nine patients admitted to the ICU in May 1995. INTERVENTIONS: None. MODEL CONSTRUCTION: We developed the model on all patients (n=989) from 37 randomly-selected ICUs using daily Sequential Organ Function Assessment (SOFA) scores. We validated the model on all patients (n=460) from the remaining 12 ICUs, comparing predicted-to-actual ICU mortality, SOFA scores, and ICU length of stay (LOS). MAIN RESULTS: In the validation cohort, the predicted and actual mortality were 20.1% (95%CI: 16.2%-24.0%) and 19.9% at 30 days. The predicted and actual mean ICU LOS were 7.7 (7.0-8.3) and 8.1 (7.4-8.8) days, leading to a 5.5% underestimation of total ICU bed-days. The predicted and actual cumulative SOFA scores per patient were 45.2 (39.8-50.6) and 48.2 (41.6-54.8). Predicted and actual mean daily SOFA scores were close (5.1 vs 5.5, P=0.32). Several organ-organ interactions were significant. Cardiovascular dysfunction was most, and neurological dysfunction was least, linked to scores in other organ systems. CONCLUSIONS: Dynamic microsimulation can predict the time course of multiple short-term outcomes in cohorts of critical illness from the profile of organ dysfunction observed on admission. Such a technique may prove practical as a prediction tool that evaluates ICU performance on additional dimensions besides the risk of death.

Interim EQ-5D-5L Value Set for Poland: First Crosswalk Value Set in Central and Eastern Europe.

OBJECTIVE: To estimate an interim five-level EuroQol five-dimensional (EQ-5D-5L) value set for Poland on the basis of the crosswalk methodology developed by the EuroQol Group. METHODS: On the basis of data from 3691 respondents from six European countries, the EuroQol Group has developed a method of obtaining interim value sets for the EQ-5D-5L by means of mapping to the available three-level EuroQol five-dimensional (EQ-5D-3L) value sets ("crosswalk" methodology). A significant part of the data in this study came from Polish respondents (n = 972; 26.3%). Poland is the first Central European country with EQ-5D-3L time trade-off-based social value set published. To obtain an interim EQ-5D-5L value set, we applied the crosswalk methodology to the Polish EQ-5D-3L value set. RESULTS: Estimated Polish values for 3125 EQ-5D-5L health states are presented. Both EQ-5D-5L and EQ-5D-3L value sets have the same range (from -0.523 to 1.000), but different means (0.448 vs. 0.380) and medians (0.483 vs. 0.403), respectively. Proportionately fewer states worse than dead were observed in the EQ-5D-5L (5.4%) value set than in the EQ-5D-3L (13.2%) value set. CONCLUSIONS: The crosswalk-based value set is available for use in EQ-5D-5L studies in Poland to calculate health state utilities. It should be considered an interim value set until values based on preferences elicited directly from a sample representative of the Polish general population become available. This study helps users of the crosswalk algorithm understand the properties of the EQ-5D-5L values generated using this method, in comparison to EQ-5D-3L values obtained with the Polish time trade-off value set. It is likely that similar results would be observed for values sets in other countries because the same crosswalk methodology applies across all countries.

[Cost-effectiveness of clopidogrel vs. aspirin treatment in high-risk acute coronary syndrome patients in Denmark]. / Omkostningseffektivitet ved clopidogrel- versus acetylsalicylsyrebehandling af højrisikopatienter med akut koronarsyndrom i Danmark.

INTRODUCTION: The aim of this study was to estimate the cost-effectiveness of clopidogrel versus aspirin (ASA) in Denmark in the secondary prevention of cardiovascular events in three high-risk CAPRIE populations: (1) patients with a history of coronary artery bypass grafting, (2) patients with a history of ischemic events and (3) patients with multiple vascular territory involvement. Additionally, the cost-effectiveness of clopidogrel versus no treatment in ASA-intolerant patients was estimated. MATERIALS AND METHODS: Clinical, epidemiological and cost data (Danish estimates) were combined in a Markov model. Estimates of transition probabilities were derived from post hoc analyses of the CAPRIE database. RESULTS: Cost-effectiveness (CE) ratios ranged from 25,445 Danish kroner per LYG (life year gained) in patients with a history of CABG to 55,503 Danish kroner per LYG in patients with multiple vascular territory involvement. The estimated cost-effectiveness ratio of clopidogrel in ASA-intolerant patients was significantly lower (3,093 Danish kroner per LYG). Sensitivity analyses showed that the order of magnitude of these CE ratios is unaffected by changes in model assumptions. CONCLUSION: In a Danish setting, clopidogrel may be considered a cost-effective treatment alternative to ASA for the secondary prevention of cardiovascular events in high-risk populations. Clopidogrel is also an effective and cost-effective treatment for ASA-intolerant patients.

Direct stenting with the Bx VELOCITY balloon-expandable stent mounted on the Raptor rapid exchange delivery system versus predilatation in a European randomized Trial: the VELVET trial.

AIMS: This study examined the six-month angiographic results of direct coronary stenting, and compared the nine-month safety, efficacy and cost of this strategy versus stenting after balloon predilatation. METHODS: In phase I of VELVET, 122 patients (mean age = 62.3 +/- 10.1 years, 77% male, 11% with diabetes) with angina pectoris or myocardial ischemia resulting from a single de novo 51% to 95% coronary stenosis underwent direct stenting. The endpoints of phase I included angiographic findings and rates of major adverse cardiac events up to six months of follow-up. In phase II, 401 patients (mean age = 61.3 +/- 10.8 years, 79% male, 16% with diabetes) with angina pectoris or documented myocardial ischemia resulting from single or multiple, de novo or restenotic, coronary lesions were randomized between direct stenting and stenting after predilatation. The immediate angiographic results, and clinical outcomes and costs associated with the two treatment strategies up to nine months of follow-up were compared. RESULTS: In phase I the mean diameter stenosis immediately before and after the procedure, and at six months was 61.7+/-9.4%, 13.5+/-6.3%, and 33.6+/-16.2%, respectively. The six-month binary restenosis rate was 11%. The overall rate of major adverse cardiac events, including two non-cardiac deaths, was 9.8%. In phase II, the success rates of the intended delivery strategies were 87.9% and 97.9% for direct stenting and predilatation, respectively (p < 0.001), while the procedural success rates were similar (93.9% vs 96.5%). Over a follow-up period of nine months, major adverse cardiac events rates were 12.0% and 10.9% in patients randomized to direct stenting and predilatation, respectively (non-significant). Analyses of the costs incurred up to nine months in each treatment group revealed a mean saving of e362 per patient in favor of the direct stenting strategy (non-significant). CONCLUSIONS: Compared with a strategy of stenting preceded by balloon dilatation, direct stenting was associated with an equivalent procedural success rate, equivalent clinical results up to nine months of follow-up, and a reduction in procedural and in-hospital costs (p < 0.0001 and p < 0.001, respectively), that was no longer significant after nine months.