Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis

Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding.The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement.Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance.In daily clinical practice clinicians are frequently presented with multiple competing treatment alternatives for the same clinical situation. In general it is accepted that when comparing several therapeutic alternatives the best evidence is derived from randomized trials. However, randomized trials are usually conducted comparing only two (or seldom three) options because inclusion of more treatment groups would require prohibitively large sample sizes and substantial increases in research costs and as a consequence, studies comparing all available treatment options at the sa