Module 9 2021

19/03/2021

Drug Development and Model Building Learning and confirming

Continuum of learn/confirm/predict at each decision point

M&S

M&S

M&S

M&S

M&S

Preclinical

Phase 1

Phase 3

Phase 4

Phase 2b

Registration Labelling

Phase 2a

FIH

POC Confirmatory

Therapeutic Index

Results relative to competitors, regional differences, therapeutic index

Efficacy

Toleration

Efficacy and safety

Toxicology

Human PK & PD

Dose/exposure-response

Covariate effects

PK-PD

Dose adjustments

Confidence in drug and disease

Uncertainty

M&S: Modelling and simulation; FIH: First-in-human; POC: Proof of concept; PK: Pharmacokinetics; PD: Pharmacodynamics

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Adapted from Lalonde RL et al. (2007) Clin.Pharmacol.Ther. 82:21-32

The Organisation for Professionals in Regulatory Affairs

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Clinical Development

Constantly seeking ways to improve the efficiency of clinical development of IMPs ● Adaptive Trial Designs of Phase 1-2 studies – Initial safety/tolerability, proof-of-concept (POC), dose finding – Where feasible, investigate as many PD parameters as possible – Continually assessing the uncertainty – Ability to modify depending upon the outcome of the assessment of uncertainty ● Modelling and simulation – Based upon PK and PD results – Informs on the IMP throughout clinical development to progress to the next phase – Used to optimise the dose and dosing regimen – Assists to design more efficient POC

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The Organisation for Professionals in Regulatory Affairs

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