Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis
1 Department of Medicine, University of Western Ontario, 800 Commissioners Rd E, London ON, N6A 5W9, Canada
2 Department of Oncology, University of Western Ontario, 800 Commissioners Rd E, London ON, N6A 5W9, Canada
3 Department of Epidemiology and Biostatistics, University of Western Ontario, 800 Commissioners Rd E, London ON, N6A 5W9, Canada
4 Department of Medicine, University of Ottawa, 501 Smyth Road, Ottawa ON, K1H 8L6, Canada
5 Department of Epidemiology and Community Medicine, University of Ottawa, 451 Smyth Road, Ottawa ON, K1H 8M5, Canada
6 Clinical Epidemiology Program, Ottawa Health Research Institute, 725 Parkdale Ave, Ottawa ON, K1Y 4E9, Canada
7 Chalmers' Research Group, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Rd, Ottawa ON, K1H 8L1, Canada
BMC Medical Research Methodology 2012, 12:3 doi:10.1186/1471-2288-12-3Published: 10 January 2012
To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery.
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.