CRED Understanding Clinical Development 2024

11/10/2024

Pharmacodynamic study designs

Study Type

Example

PD measures

FIH

SAD/MAD in healthy subjects

Natural biomarkers Ex vivo stimulation Response to challenge Oral glucose test Iohexol measured GFR

DDI

Metformin with transporter inhibitors Scopolamine injection in healthy seniors to mimic Alzheimer's

Disease model

EEG, cognitive tests

Study in patients

Any type

Mechanism related biomarkers to correlate with clinical endpoints Mechanism related biomarkers to measure relative responses in vivo Search for additional prognostic or predictive biomarkers, DNA, etc.

Comparison study

Comparison with similar drug

Exploratory study

Add-on biomarker samples for retrospective analysis

The Organisation for Professionals in Regulatory Affairs

15

Definition of Biomarkers

Biomarker: “ a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention ”

Type 0 – markers of natural history of a disease, correlate with symptoms

Type I – based on mechanism of action of the drug, may not be associated with the clinical outcome

Type II – predict clinical outcome, surrogate endpoints (a biomarker is intended to substitute for clinical endpoint)

The Organisation for Professionals in Regulatory Affairs

Frank R, Hargreaves R. 2003.

16

8