Since Crystal City VI in 2015 when the phrase 'Biomarker assays are not PK assays' was first presented, and thereafter uttered countless times, there have been numerous scientific forums devoted to highlighting that biomarker assays need to be developed and validated to meet their specific context of use and therefore require a different approach from PK assays which serve a singular context of use. For those who have been deeply entrenched in these discussions it feels as though that there can be nothing more to say on this issue. Unfortunately, the reality remains that a large proportion of biomarker assays are still developed and validated according to PK assay approaches and guidance. Indeed, solution providers continue to publish lists of 'validated' biomarker assays on their websites, even though prospective clients will use those assays to support a variety of contexts of use, each of which could require completely different assay performance characteristics.
A misperception that persists among many is that fit-for-purpose biomarker assay validation implies inferior rigor and that validation performed as for a PK assay somehow constitutes 'full validation' that will serve all contexts of use. This is untrue and can result in generation of misleading or erroneous data and subsequent misinterpretation or overinterpretation of biomarker data, negatively impacting the course of drug development. Although assay performance parameters of interest are quite similar for (relative) quantitative biomarker assays and PK assays, the approaches used to interrogate these parameters for PK assays is fundamentally incorrect for biomarker assays.
This presentation will provide clarity for scientists seeking to develop, validate and implement biomarker assays, and the regulators who review them by highlighting the what, why and how that differentiate PK and biomarker assays. • What - the key assay performance parameters of interest for both PK and biomarker assays will be described, highlighting the parallels between them. • Why - why these parameters are important for both (relative) quantitative biomarker and PK assays will be explained with emphasis on why the approaches to evaluate these parameters are different for biomarker assays. • How - how to evaluate each parameter for biomarker assays and how the differences in approach for biomarker assays ensure that the data generated are able to meet the needs of the specific context of use will be outlined. Additionally, in cases where context of use may initially be unknown, how to leverage the demonstrated assay performance data to inform the assay's suitability for potential future contexts of use will be presented.
Learning Objectives:
Understand the key assay performance parameters that need to be evaluated to develop and validate biomarker assays suited for their specific context of use
Apply appropriate scientific approaches to interrogate key assay parameters and demonstrate suitability for context of use
Understand how to analytically characterize assay performance for a biomarker assay in the absence of context of use and how that informs future contexts of use that may be supported