Defining drug response for stratified medicine.

Area of Science:

• Pharmacogenomics
• Clinical Pharmacology
• Biomarker Discovery

Background:

• Stratified medicine aims to improve drug benefit:risk by identifying patient groups with varied responses.
• Biomarkers are crucial for targeted prescribing, but variability in drug efficacy and safety poses challenges.
• Inadequate characterization of response variability can limit the clinical utility of identified biomarkers.

Purpose of the Study:

• To discuss the complexities in investigating variability of drug efficacy and safety.
• To highlight the importance of a priori consideration of these complexities.
• To emphasize how standardizing phenotypes enhances biomarker discovery for clinical impact.

Main Methods:

• Review and discussion of factors contributing to inter-individual variability in drug response.
• Analysis of challenges in biomarker identification for stratified medicine.
• Exploration of strategies to improve the efficiency of patient stratification.

Main Results:

• Variability in drug efficacy and safety is multifactorial, impacting biomarker utility.
• Standardized phenotypes are essential for robust biomarker discovery.
• Proactive consideration of variability enhances the efficiency of stratification.

Conclusions:

• Addressing the complexities of drug response variability is critical for successful stratified medicine.
• Standardization of phenotypes and a priori investigation of variability improve biomarker identification.
• This approach increases the likelihood of identifying clinically impactful biomarkers.