P227: Clinical Biomarkers: Implementing the Principles of Context-Of-Use for Biomarker Bioanalysis in Support of Drug Development
Poster Presenter
Sam Willcox
Section Manager - Large Molecule Bioanalysis
ACM Global Laboratories United Kingdom
Objectives
Biomarkers play an integral role in all phases of drug development, it is vital that the context of use for the bioanalytical data is established and is made known to all stakeholders to ensure that biomarker assays are characterized and validated/qualified accordingly.
Method
Biomarker data at ACM global laboratories is generated by a number of platforms/techniques such as colorimetric and electrochemiluminescence based ligand binding assays, liquid chromatography–mass spectrometry and luminex immunoassays.
Results
Biomarkers can fall into many classes such as diagnostic, predictive, pharmacodynamics, safety monitoring or susceptibility biomarkers. The context of use for pharmacokinetic assays is always clear, however for biomarker assays the scientific or safety decision that will be made from the data produced, needs to be determined to ensure the appropriate data is collected and utilised effectively. This can often differ for the same biomarker in different clinical situations. Once a context of use has been established, the bioanalytical strategy can be assessed and a decision made on the platform, characterisation, sensitivity requirements and assay validation/qualification approach. Establishing a context of use and applying this to the bioanalytical strategy is critical to ensure the right assays are set up, used and validated/qualified to the appropriate level, the broad application of the PK validation approach used by many within the industry is not only incorrect but also unachievable in many cases. As a CRO, offering multiple service lines in the bioanalysis of biomarkers whilst working with stakeholders to evaluate the context of use of can help identify at an early stage of drug development the most appropriate data set to provide to be used to make ongoing clinical decisions. The context of use of a biomarker within a particular setting can change over time and it is important this is acknowledged and communicated correctly and effectively throughout the drug development lifecycle. Results from biomarker assays can give researchers and clinicians evidence about the safety and efficacy of treatments. They can be used in the initial drug discovery and development phase to help identify likely treatment candidates to surrogate endpoints in clinical trials helping to reduce the risk of harm to subjects. The quality of those results depends entirely on the bioanalytical strategy and how it is executed.
Conclusion
Evaluation of the context of use for a biomarker assay requires a definition of the purpose for which the data is to be generated. This can include understanding the pharmacological effect and expected biological variance in addition to what the data will actually be used for e.g. a primary or secondary endpoint in clinical trials. The discussion around implementing a context of use strategy has been at the forefront of industry discussion within the European Union for a number of years. It is important all stakeholders in drug development from clinical pharmacologists to health authorities, bioanalysts to statistical teams, understand the significance of how the data produced and its appropriateness for the associated decision making it is supporting.
The context of use is for biomarker data often difficult to establish where multiple stakeholders are involved and key experts are not included within decision making processes. However, the way biomarker data is utilised and interpreted is critical for patients. If no context of use is established or if the incorrect context of use is applied, this will influence the bioanalytical strategy implemented, and ultimately the quality of the data produced. This can lead to unsuitable platform selection, inappropriate sensitivity, incorrect application of acceptance criteria, poor precision and reproducibility, a waste of resources and critical patient samples; it can cause wrong decisions and ultimately negatively affect drug development. Having an upfront context-of-use or a strategy to determine this means the most appropriate bioanalytical strategy can be selected. This can streamline analysis and give all stakeholders confidence in the data generated which can be used in support of efficacious safe drugs for patients.
