The subtle differences between biomarkers, diagnostics, surrogate endpoints and companion diagnostics in terms of regulatory requirements can be confusing, and nearly any misstep in the development process can lead to failure.
Methods: Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume 82 cm3 were analyzed. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints.If the chosen regulatory path for a biomarker is as a companion diagnostic or surrogate endpoint, biomarker validation is a requirement.Validation through clinical trials provides evidence that the methods used for a particular analyte support the intended use of the marker with sufficient statistical power to be approved by the FDA (or other international regulatory agencies) before entering the market.The use of specific biomarkers as endpoints in clinical trials is only justified when well characterised and the analytical methodology validated to the appropriate level to ensure key biomarker data is reliable.
The need for a standardised approach towards validation is becoming increasingly important given this recent surge in the biomarker development pipeline.
The scale on the bottom indicates the relationship between increased signal intensity and color.
Characteristic protein expression patterns are observable in individual cells, communities of cells, organs, and whole organisms.
Guidance for Industry: Pharmacogenomic Data Submissions The use of "companion diagnostics" to drive molecularly targeted drug development also requires that the "diagnostic" be clinically validated through the FDA's PMA or 510(K) process.
In both of these instances the biomarker must be analytically validated (inclusive of the test platform, reagents, etc.).
Scientists at PNNL are developing antibody microarray technology for the validation of biomarker profiles.