CRED Understanding Clinical Development 2024

08/10/2024

PK modelling

• Almost all PIPs include some form of modelling

Main functions are:

•

• Prediction of appropriate paediatric starting doses

• Confirmation that the doses given result in appropriate exposure

• Population-based modelling (PopPK) scales downwards from adult data

• Typically most useful from adolescents down to 2 years of age

• Physiologically-based modelling (PBPK) may be more suitable for immature organ systems

• Typically most useful from birth to <2 years

PK modelling is a specialist discipline likely to require expert input

The Organisation for Professionals in Regulatory Affairs

21

Extrapolation

• Purpose is to facilitate conclusions on benefit-risk with limited paediatric clinical data (partial extrapolation) or no paediatric clinical data at all (full extrapolation) in the age group concerned

• Must establish that the “extrapolation concept” is valid

•

Disease is similar across age groups

• Relationship between dose, exposure, PD effects and clinical responses is understood

Propose an “extrapolation plan”

•

• What paediatric data will be generated?

• How will those data be used to infer (or reject) the validity of extrapolation?

• What will the acceptance / rejection criteria be?

Not easy and not necessarily cheap…

…but you can do a lot of extrapolation work for the time, effort and cost of studying children in clinical trials

Still an evolving field

The Organisation for Professionals in Regulatory Affairs

22

11