A perspective on challenges and issues in biomarker development and drug and biomarker codevelopment

Abstract

A workshop sponsored by the National Cancer Institute and the US Food and Drug Administration addressed past lessons learned and ongoing challenges faced in biomarker development and drug and biomarker codevelopment. Participants agreed that critical decision points in the product life cycle depend on the level of understanding of the biology of the target and its interaction with the drug, the preanalytical and analytical factors affecting biomarker assay performance, and the clinical disease process. The more known about the biology and the greater the strength of association between an analytical signal and clinical result, the more efficient and less risky the development process will be. Rapid entry into clinical practice will only be achieved by using a rigorous scientific approach, including careful specimen collection and standardized and quality-controlled data collection. Early interaction with appropriate regulatory bodies will ensure studies are appropriately designed and biomarker test performance is well characterized.

Figure 1

Considerations for drug and biomarker codevelopment. The schematic encompasses the entire life cycle for codevelopment of a drug and biomarker combination from early selection and validation of the biomarker target through preclinical and nonclinical development of the drug and biomarker assay to clinical evaluation of the drug and biomarker assay combination. The center of the diagram lists major steps in the process for the biomarker and assay (left) and the drug (right). The boxes on the left list considerations for the biomarker and biomarker assay at the various phases of development. The boxes on the right list considerations for the drug and drug–biomarker diagnostic combination. The considerations include recommendations for moving development forward and factors that should be taken into account in formulating the development strategy. As an assay and agent progress through the phases of development, continued codevelopment depends on greater confidence in the robustness and performance characteristics of the assay and stronger evidence for correlation of the biomarker with clinical benefit from the agent. At each stage in the development process, there may be different expectations for the marker (its “fitness for purpose”); as development progresses, so do the risks and therefore the expectations and requirements for the marker increase. FDA = Food and Drug Administration.