A former boss of mine used to compare tackling the bioanalysis of biomarkers to a soldier in trench warfare jumping on an unexploded grenade to save their comrades. While I may not be that brave or sacrificial, I do feel compelled to commend a recent paper from the European Bioanalysis Forum (EBF) on this topic. Specifically, the EBF's recommendations on requiring a context-of-use (CoU) statement for the successful development and validation of biomarker assays. You can find the White Paper at https://doi.org/10.1080/17576180.2024.2376436, K.J. Cowan et al., Bioanalysis Vol 16 (16), pp. 835-842.
This isn't the first paper on CoU in biomarker bioanalysis, as we've been discussing the concept for over a decade. Early in the paper, the authors address the dilemma of "what is slowing down the implementation of CoU principles for biomarker application," a question that bioanalysts should carefully consider. The reason proposed is that we don’t typically have a useful and comprehensive CoU statement that enables an appropriate bioanalysis strategy. A key element of this paper is its practical guidance on deriving such a CoU statement. To put it simply, deriving a CoU statement should be the first step in any biomarker bioanalysis program.
This resonated with me because I've often seen bioanalysts struggle to develop and validate biomarker assays without a clear understanding of the intended use of the data. The challenge is frequently to validate the assay to "fully validated BMV criteria" with the best possible sensitivity. This becomes even more complicated with fit-for-purpose terminology, leading us to optimize an assay to the nth degree without knowing if it will meet the intended purpose or if it will overperform for the end use.
The paper outlines six key elements (plus a seventh on communicating the outcome) that should be included in a CoU statement: 1) identifying the biomarker, 2) categorizing it, 3) defining its use/purpose, 4) explaining the biological context, 5) specifying the change or treatment effect, and 6) conveying the impact the biomarker measurement will have on any decisions made with the data. These six steps provide a template for creating a CoU statement.
Another crucial takeaway from the paper is the question of who owns the CoU statement. Spoiler alert: it's NOT the bioanalyst. The bioanalyst's role is to develop a bioanalytical strategy based on the CoU statement. The paper compellingly argues that the stakeholders who will use the biomarker data (clinicians, pharmacologists, biomarker team leads, or others) should write the CoU statement based on the six key elements mentioned.
Overall, I highly recommend this paper if you are involved in regulated bioanalysis. It offers a practical perspective that extends beyond biomarkers and provides an alternative to PK-based a priori criteria, which are not universally appropriate for biomarker assays. There's no need for me to dissect the paper further—go read it. It's an accessible and very helpful guide for discussions about what is appropriate for your next biomarker bioanalysis assay development and validation.