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.
