Population PK studies are integral components of clinical trials with many patients, such as a Phase 3 trial, and these studies involve collection of a few blood samples from each trial participant or from a smaller subgroup of participants selected at random. Computer simulation studies are conducted in advance to describe the number of samples that will be collected from participants and the collection time and frequency of blood sample collection. Population PK studies do not require extensive criteria for design compared to other methods, and these studies are readily adaptable to clinical settings. Population PK modeling provides a means to obtain PK data after administration of a drug from a limited amount of data collected from a population of treated participants. Population PK modeling provides a capability in excess of statistical modeling of sparse data, and it is a powerful tool that can be used to investigate variables affecting inter-individual PK parameter variability. PK data derived from populations can be used to derive the most efficacious and safe dosing regimens. The advantages of population PK/PD modeling and simulation for drug combinations include: 1) clinical trial design optimization for efficacy assessment of drug combination partners; 2) population PK/PD model development validation using limited internal data; 3) PK/PD model external validation utilizing data derived from independent studies; and 4) prospective clinical drug evaluation. PK/PD model outputs can be used to optimize specific drug dosing regimens that can be used to develop guidelines for dosing other drugs, either on market or newly developed, with similar drug mechanism of action or disposition. While the need to conduct modeling to describe drug disposition through profiling PK parameters is clearly established as an essential tool, there is also a need for population level modeling, particularly incorporating effect pathways of drug combination.
Keywords: Children, drug combination, phase 2 clinical trials, phase 3 clinical trials, population, population evaluation, population PD, population PD modeling, population PK, population PK modeling, population PK/PD, population PK/PD modeling.