In drug development, biomarker assays may serve purposes other than the ones they serve in clinical studies. This possibility has been explored by John L. Allinson, vp of biomarker laboratory services at ICON’s development solutions service division. “While diagnostic assays are used for the purpose of routine safety or efficacy assessments (under recognized global clinical laboratory accreditation schemes), there are many other uses that their versatility lends them to,” says Allinson. “These include, but are not limited to, drug candidate attrition and refinement, protocol design, dose selection, PK/PD modeling, patient stratification, companion diagnostics, post-approval surveillance, and market differentiation.
“With such a wide range of applications, often the biomarker assay may not require as much development or long-term robustness (sometimes known as ‘exploratory’ markers and assays), while other uses may actually require more intensive attention to things like precision in parts of the analytical range not associated with significant diagnostic assessment but where more subtle changes need to be characterized, for instance, due to pharmacodynamic effects of specific drugs.”
Allinson says that, therefore, in drug development biomarker assays, more or less attention can be applied to certain assay performance characteristics such as precision and limits of quantification. This leads to a tiered approach to assay validation in drug development assays versus a very well-established and standardized approach to diagnostic assays, which is required for their accreditation.
Biomarker assays are not usually off-the-shelf services. “To be absolutely certain that assays are fit-for-purpose, that is, appropriate for their intended use, there must be people in the service provision who understand the assay’s clinical utility. Matching assay and technology choice to attain a suitable assay performance that enables the correct interpretation of the results to be made is absolutely critical to providing a suitable biomarker assay service. Once these decisions are made, applying a suitable fit-for-purpose validation approach to each assay is the next critical component.”
When these careful and methodical approaches are not followed, trouble can ensue. “During my 20 years in contract research, I personally acquired knowledge of the many ways laboratories may produce data that leads to incorrect clinical decisions,” recalls Allinson. “Laboratories may modify diagnostic assays without understanding how those assays were developed.
“An example is the replacement of calibration reference material with substances that are not recognized international reference materials. If the substances behave differently from the appropriate reference material, they can give rise to different concentration data. Depending on the use of the results, erroneous data can have very serious consequences.”