Biomarkers in Drug Development and Pharmacometric Modeling

The use of biomarkers in conjunction with pharmacometric models has the potential to improve the drug development process and pharmacotherapy. Biomarkers serve several purposes such as stratification of patients for clinical trials, predict patient response, serve as links between exposure and clinical endpoint in clinical trial simulation, and serve as a surrogate endpoint in a clinical trial when validated. Biomarkers may mature from being a natural history marker to eventually become a surrogate endpoint. In some disease states where the observation of the final clinical endpoint is delayed, it is desirable to use a surrogate endpoint to expedite the drug development process. The establishment of a biomarker as a surrogate endpoint requires several characteristic and must meet statistical criteria. An example of combining a biomarker with a PK-PD-Outcomes model to determine the structure of a phase 3 clinical trials is presented.