From Biomarker Discovery to Clinical Use

As development progresses, the clinical specificity and sensitivity of the biomarker is continuously evaluated. A great point to consider in this regard is the value of biobanking for retrospective analyses and potential discovery of novel biomarkers. During the development process, it is important to consider pre-analytical factors which can influence the process and integrity of the biomarker. These include status of the patient from which the sample is derived, biospecimen collection, handling and storage, and attention to freeze-thaw cycles of the sample.

Analytical validation is characterized by analysis of the biomarker assay performance with the goal of ensuring a repeatable measurement with low variance and good sensitivity and specificity. Multiple parameters are assessed during this phase, including selectivity, accuracy, precision, recovery, sensitivity, reproducibility, and stability. Depending on the intended use of the biomarker assay certain standards must be met, such as the Clinical Laboratory Improvement Amendments (CLIA) for assays to be used for testing human samples.

A biomarker validation according to the Clinical Laboratory and Standards Institute (CLSI) guidelines can further reduce the risk of a technical or analytical failure, thus increasing the utility of the biomarker assay, and is required for qualification and approval of the biomarker assay.

It is important to consider that most biomarkers often do not make it through discovery, validation and implementation due to various reasons. Biomarker development may fail both because of technical and hypothesis-driven failures. The cost of bringing a biomarker to the market is extremely high, and often needs a co-development process including a drug.

Many drugs unfortunately fail in development due to lack of demonstrating efficacy, and so do biomarker candidates. In addition, changing clinical practice is a big hurdle, which takes many years, thus the return-of-investment from investing in both biomarkers and drug development is often lacking for biomarkers with limited investments.

Additionally, it is easier to do biomarker discovery with a bigger platform such as SomaScan and Olink, but the investment taken from discovery to refinement over many studies, with CLSI technical validation along the way (Figure 1), is long and costly. Moreover, submission to regulatory agencies in relation to formal qualification of biomarkers is long, expensive and requires substantial data to be generated, which further complicates the possibilities for smaller companies and research groups.