Biomarkers are increasingly becoming popular among clinicians to predict, assess and treat diseases and medical conditions. As the name suggests, biomarkers are biological markers that can be objectively measured and evaluated as indicators of pathogenic or normal biological processes or responses to a therapeutic drug. Hence, proteins and genes or routine measurements such as blood pressure and blood flow can be biomarkers. Moreover, imaging findings such as MRI and X-rays qualify as biomarkers.
In some diseases, such as cancer, biomarkers often help clinicians make informed decisions regarding chemotherapy and other available treatment options. Therefore, it is crucial that biomarkers should not only be reliable indicators but highly accurate also. This need for accuracy has made biomarker assay development and validation one of the most vital aspects of biomarker analysis. That said, in this series of posts, titled “CRO in 2022”, we shall explore the importance of biomarker validation in drug discovery.
What is biomarker validation, and how its importance continues to grow in drug discovery?
Biomarker validation comprises the testing of potential biomarkers for accuracy and consistency. It also refers to the ability of a biomarker to provide crucial indicators about health or diseases. Although biomarker validation does not have a single measure to determine its validity, there are specific criteria that biomarker services need to accomplish to determine its clinical validity. Out of the several validation parameters, specificity, sensitivity, analytical and clinical validity are the four critical components for biomarker validation. Let us explore these parameters in detail and understand how attaining them will help the drug discovery process.
Biomarker specificity and sensitivity are two sides of the same coin. Hence, most often, they are considered together in biomarker analysis. During drug discovery, a test is considered specific if it shows a positive result only in the presence of the biomarker of interest and negative when the biomarker is absent. On the other hand, sensitivity refers to the ability to provide accurate results when the test is performed for a biomarker.
Analytical validity ensures that a particular test measures the intended target biomarker. Hence, specificity and sensitivity are core components of analytical validity. Any assay intended to measure the target biomarker must demonstrate analytical validity for its usefulness in routine analysis. Generally, for a newly developed test in drug discovery, the analytical validity is assessed by comparing it with the best available test for that biomarker.
Clinical validity forms another crucial aspect of biomarker validation. Clinical validity ensures that a test can predict a clinical outcome. Generally, a clinically valid test is associated with improvement in patient health. However, if a test is highly sensitive but not specific enough, it will be of no use in drug discovery. Hence, biomarker CROs ensure that a generated test is both analytically and clinically valid.
The road ahead
With technological advances, bioanalytical companies and research organizations are going to grow their databases with robust biomarkers. However, to use them in clinical settings, these biomarkers should be adequately validated. Eventually, biomarkers reaching clinical settings will be backed by thorough biomarker validation.