Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

How strong is the evidence for the use of perioperative blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials

Objective To determine the effect of perioperative blocker treatment in patients having non-cardiac surgery. Design Systematic review and meta-analysis.Data sources Seven search strategies, including searching two bibliographic databases and hand searching seven medical journals.Study selection and outcomes We included randomised controlled trials that evaluated blocker treatment in patients having non-cardiac surgery. Perioperative outcomes within 30 days of surgery included total mortality, cardiovascular mortality, non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke, congestive heart failure, hypotension needing treatment, bradycardia needing treatment, and bronchospasm. Results Twenty two trials that randomised a total of 2437 patients met the eligibility criteria. Perioperative blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative blockers showed a relative risk for bradycardia needing treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27 (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66). Conclusion The evidence that perioperative blockers reduce major cardiovascular events is encouraging but too unreliable to allow definitive conclusions to be drawn...