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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, University of Western Ontario, London ON, Canada. alejandro.lazo@alumni.uottawa.ca
Alejandro
A
Lazo-Langner
Marc A
MA
Rodger
Nicholas J
NJ
Barrowman
Tim
T
Ramsay
Philip S
PS
Wells
Douglas A
DA
Coyle
D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000191:economics; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000191:economics; D001499:Bayes Theorem; D003362:Cost-Benefit Analysis; D003657:Decision Making; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D015201:Meta-Analysis as Topic; D009010:Monte Carlo Method; D009985:Orthopedics / Q000191:economics / Q000379:methods; D010314:Partial Thromboplastin Time; D010919:Placebos; D019106:Postoperative Hemorrhage / Q000209:etiology; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010919:Placebos