Reliable diagnostic, prognostic, predictive, pharmacodynamic, and pharmacokinetic biomarkers are critical to assure correct patient selection, drug dosing, and monitoring. Being able to identify the most effective biomarkers and then utilize them to stratify patients and evaluate therapeutic benefit can reduce both drug development time, clinical trial sizes and facilitate more rapid regulatory approvals and time to market. As such, in the early stages of drug development, a drug developer should begin to evaluate biomarkers for potential diagnostic application in parallel with the development of the therapeutic drug itself. Early research will focus on identifying potential biomarkers based on knowledge of the drug’s mechanism of action. The goal is to identify measurable analytes that accurately correlate to an early biological effect; i.e., a measurable change in normal biology. The quality of the biomarker assay need only fulfil the requirements necessary for internal decision-making. How a biomarker assay is further applied to a drug's development, e.g., as a clinical endpoint (primary, secondary or exploratory) in a clinical protocol, will determine when an assay should evolve from research quality to a clinical diagnostic test or even a Companion Diagnostic (CDx). This presentation will provide guidance on how to navigate through this process.
1. How do you determine what level of validation is required to measure a biomarker?
2. Recommendation for assay validation of a biomarker method supporting:
i. An exploratory endpoint
ii. A pharmacodynamic endpoint
iii. Patient selection, decisions, or safety endpoint