Continuous infusion chemotherapy as a radiation-enhancing agent for yttrium-90-radiolabeled monoclonal antibody therapy of a human tumor xenograft

The motivation behind the creation of the International Normalized Ratio (INR) was to improve interlaboratory comparison for patients on anticoagulation therapy. In principle, a laboratory that reports the prothrombin time (PT) as an INR can standardize its PT measurements to an international reference thromboplastin. Using probability theory, the authors derived the equation for the probability distribution of the INR based on the PT, the International Sensitivity Index (ISI), and the geometric mean PT of the reference population. With Monte Carlo and numeric integration techniques, the model is validated on data from three different laboratories. The model allows computation of confidence intervals for the INR as a function of PT, ISI, and reference mean. The probabilistic model illustrates that confidence in INR measurements degrades for higher INR values. This occurs primarily as a result of amplification of between-run measurement errors in the PT, which is inherent in the mathematical transformation from the PT to the INR. The probabilistic model can be used by any laboratory to study the reliability of its own INR for any measured PT. This framework provides better insight into the problems of monitoring oral anticoagulation.