Dose Selection for Drug Trials Using Wolfram SystemModeler and Mathematica
Explore the contents of this article with a free Wolfram SystemModeler trial. During the last decades, the development and use of therapeutic monoclonal antibodies (mAbs) have grown rapidly. Today, more than 30 different mAbs are successfully used in the clinic—playing important roles in treating complex diseases such as cancers and auto-immune disorders—and more than 200 are in clinical trials. The history of mAbs has, however, not been without problems. In 2006, a first-in-human clinical trial of an mAb, aimed at treating leukemia and rheumatoid arthritis, went terribly wrong. Although the trial was run according to an approved protocol, all volunteers receiving the drug had severe inflammatory reactions and multiple organ failure. The tragic event shocked the medical community and highlighted a very important issue: how do you select a safe starting dose in first-in-human trials? Now, as you may guess, the complete answer to this question is not an easy one. It's also beyond the scope of this blog post. However, as a consequence of the dramatic happenings in 2006, the European Medicines Agency (EMEA) recently published new guidelines to address the issue of starting dose selection in first-in-human trials. Interestingly, the guidelines recommend that the use of modeling and simulation should play an integral part in the selection process, and in this post I thought we would study what such an approach might look like using Wolfram SystemModeler and Mathematica.