Study DesignGlossary Term
ICH E4
The study of how a drug affects the body, including its mechanism of action, biochemical and physiological effects, and the relationship between drug concentration and effect.
Pharmacodynamics examines the relationship between drug exposure and biological response, characterizing what a drug does to the body rather than what the body does to the drug. This discipline encompasses the drug's mechanism of action at the molecular level, its effects on cellular and organ function, and the relationship between concentration and response. While pharmacokinetics asks how much drug reaches the site of action, pharmacodynamics asks what happens when it gets there.
Pharmacodynamic assessments employ biomarkers to measure drug effects at various biological levels. Molecular biomarkers might include receptor occupancy, enzyme inhibition, or gene expression changes. Cellular biomarkers could measure changes in cell signaling, proliferation, or death. Physiological biomarkers assess functional effects such as blood pressure reduction, glycemic control, or tumor shrinkage. These measurements establish proof of mechanism, demonstrating that the drug engages its intended target, and proof of concept, showing that target engagement produces the desired biological effect.
The integration of pharmacokinetics and pharmacodynamics through PK/PD modeling provides powerful tools for dose optimization. By mathematically relating drug exposure to biological response, these models can predict the effects of different dosing regimens, identify the exposure levels associated with efficacy and toxicity, and support dose selection for subsequent trials. This quantitative approach to dose-response characterization has become increasingly important in modern drug development, enabling more efficient clinical programs and more rational dose selection than traditional empirical approaches.
Target engagement
"Pharmacodynamic assessments using positron emission tomography confirmed greater than 90% receptor occupancy at the proposed therapeutic dose, establishing proof of mechanism for the novel antipsychotic."
PK/PD modeling
"The integrated PK/PD model demonstrated a clear exposure-response relationship for the diabetes drug, predicting that trough concentrations above 50 ng/mL were associated with clinically meaningful HbA1c reductions."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.
ICH E4
The study of how a drug affects the body, including its mechanism of action, biochemical and physiological effects, and the relationship between drug concentration and effect.
Pharmacodynamics examines the relationship between drug exposure and biological response, characterizing what a drug does to the body rather than what the body does to the drug. This discipline encompasses the drug's mechanism of action at the molecular level, its effects on cellular and organ function, and the relationship between concentration and response. While pharmacokinetics asks how much drug reaches the site of action, pharmacodynamics asks what happens when it gets there.
Pharmacodynamic assessments employ biomarkers to measure drug effects at various biological levels. Molecular biomarkers might include receptor occupancy, enzyme inhibition, or gene expression changes. Cellular biomarkers could measure changes in cell signaling, proliferation, or death. Physiological biomarkers assess functional effects such as blood pressure reduction, glycemic control, or tumor shrinkage. These measurements establish proof of mechanism, demonstrating that the drug engages its intended target, and proof of concept, showing that target engagement produces the desired biological effect.
The integration of pharmacokinetics and pharmacodynamics through PK/PD modeling provides powerful tools for dose optimization. By mathematically relating drug exposure to biological response, these models can predict the effects of different dosing regimens, identify the exposure levels associated with efficacy and toxicity, and support dose selection for subsequent trials. This quantitative approach to dose-response characterization has become increasingly important in modern drug development, enabling more efficient clinical programs and more rational dose selection than traditional empirical approaches.
Target engagement
"Pharmacodynamic assessments using positron emission tomography confirmed greater than 90% receptor occupancy at the proposed therapeutic dose, establishing proof of mechanism for the novel antipsychotic."
PK/PD modeling
"The integrated PK/PD model demonstrated a clear exposure-response relationship for the diabetes drug, predicting that trough concentrations above 50 ng/mL were associated with clinically meaningful HbA1c reductions."
The fraction of an administered dose of a drug that reaches the systemic circulation unchanged, and the rate at which this occurs.
A group of participants in a clinical trial who receive a comparator treatment, placebo, or no treatment to serve as a baseline for evaluating the effects of the investigational intervention.
A clinical trial design in which participants receive multiple treatments in sequence, with each participant serving as their own control by receiving all study treatments during different periods.
A systematic approach to increasing the dose of an investigational product during a clinical trial, typically employed in early-phase studies to identify safe and potentially effective dose levels.
A clinical trial in which both the participants and the investigators are unaware of the treatment assignments, providing maximal protection against bias in the conduct and assessment of the study.