Advances in risk-benefit evaluation using probabilistic simulation methods: an application to the prophylaxis of deep vein thrombosis

• Published in: Journal of clinical epidemiology Vol. 57; no. 8; pp. 795 - 803
• Main Authors: Lynd, Larry D., O'Brien, Bernie J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-08-2004; Elsevier; Elsevier Limited
• Subjects: Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Confidence intervals; Data interpretation; Decision Support Techniques; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug therapy; Enoxaparin - adverse effects; Enoxaparin - therapeutic use; Epidemiology; Estimates; General aspects; Hemorrhage - chemically induced; Heparin - adverse effects; Heparin - therapeutic use; Humans; Hypotheses; Hypothesis testing; Medical sciences; Methodology; Methods; Molecular weight; Monte Carlo Method; Monte Carlo simulation; Mortality; Preferences; Probability; Prophylaxis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Random variables; Risk; Risk assessment; Risk Assessment - methods; statistical; Studies; Thromboembolism; Uncertainty; Venous Thrombosis - prevention & control; Monte Carlo method; Risk; Uncertainty; Risk assessment; Data interpretation; Human; statistical; Methodology; Deep vein thrombosis; Cardiovascular disease; Epidemiology; Venous disease; Vascular disease; Prevention; Benefit risk analysis; Simulation; Risk factor; Application method; Probabilistic model; Public health
• ISSN: 0895-4356; 1878-5921
• DOI: 10.1016/j.jclinepi.2003.12.012

To demonstrate the use of probabilistic simulation modeling to estimate the joint density of therapeutic risks and benefits. Published data are used to introduce the risk–benefit acceptability curve as a novel method of illustrating risk–benefit analysis.
Using published data, we performed a second-order Monte Carlo simulation to estimate the joint density of major bleeding and deep vein thrombosis (DVT) secondary to enoxaparin or unfractionated heparin. Within a Bayesian framework, beta-distributions for the probabilities of experiencing a DVT and major bleed were derived from the clinical trial, and incremental probabilities were calculated.
The incremental risk–benefit pairs from 3,000 simulations are presented on a risk–benefit plane. To accommodate different risk preferences, the results are also illustrated using a risk–benefit acceptability curve, which incorporates different risk–benefit acceptability thresholds (μ), or the number of major bleeds one is willing to accept in order to avert one DVT. Finally, a net-benefit curve is used to illustrate the risk–benefit ratio and the derivation of 95% confidence intervals around the ratio.
Modern simulation methods permit the estimation of the joint density of risks and benefits with their associated uncertainty, and within a Bayesian framework, facilitate the estimation of the probability that a therapy is net-beneficial over different preference thresholds for risk–benefit trade-offs.