Biomedical research is increasingly being dominated by omics, which stem from genomics, or the study of the genome, and now include smaller areas of investigation such as phosphoproteomics, clinomics, and immunomics. A previous commentary (IVD Technology, March 2005) examined using proteomic technology to develop IVDs, and placed some emphasis on applying this technology to identify biomarkers. This article also discussed that using proteomic technology did not ensure success, that any direct application of proteomic technology in IVDs is unlikely in the next decade, and that proteomics could be useful in identifying and validating biomarkers for use in laboratory diagnostics. The following article further dwells on biomarkers and biomarker development, and suggests that biomarkers are in fact diagnostic analytes with a new spin (or old wine in new bottles).
Patricia M. Wagner is an assistant professor of English at Victor Valley College (Victorville, CA). She is also active with extramural continuing education courses on technical writing in the United States and Europe. She can be reached at firstname.lastname@example.org.
A biomarker is defined as “a substance used as an indicator of the presence of material of biological origin, a specific organism, or a physiological condition or process; a diagnostic indicator of a predisposition to a medical condition.” While this definition would seem to relate logically to the medical field, that is not necessarily always the case. For example, a large amount of work involving biomarkers is found in the geological literature concerning compounds found in crude oil that are derived from once-living organisms. Nonetheless, the term biomarker is more prevalently used in biomedical research in which a biomarker can be defined as a substance or event within an organism that can be used in a prognostic or diagnostic manner. With the recent exuberance in using the term biomarker, it is easy to forget that this term has been used for at least 30 years. Even though the term biomarker is neither new nor unique, this does not mean that the concept is not valuable. However, just because a biomarker is identified by using an omics technology, there is no reason to assume that it does not have to follow the rules of diagnostic product development, including design control.
From Identification to Diagnostic Use
With the exception that mass spectrometric pattern recognition such as surface-enhanced laser desorption and ionization (SELDI) may be useful, a discovery technology, mass spectrometry, and orthogonal separation techniques are unlikely to form the technical basis of an assay. It will be increasingly difficult to defend such specialty laboratories focusing on molecular diagnostics, and a new assay will be more successful if it fits into an existing laboratory format. In other words, the assays that form the basis of molecular diagnostics will become increasing useful, but will have maximum value within the existing clinical laboratory structure. Within the context of the current discussion, using a newly discovered biomarker as a laboratory analyte in a clinical lab will likely involve developing an immunoassay or other type of binding assay. Finally, coupling a new biomarker with an existing biomarker will add considerable power to an assay. Using pattern recognition employing SELDI technology is an example of using multiple biomarkers.
It is encouraging to see investigators recognizing the need to place more rigor on using proteomics to identify biomarkers for use in diagnostics. The biggest challenge is using sufficient numbers of samples to determine normal values. Even though proteomic experiments take time and money, that does not relieve the investigators from the responsibility of following certain rules. Thirty years ago, 200 independent subjects would have been required to obtain a normal value. More recently, the concept of normal is more complex, and has been replaced by concepts of a reference interval and a relevant set of reference values.
It is a bit of a mistake to think that describing a clinical laboratory analyte (old wine) as a biomarker (new bottle) does anything for the quality of a diagnostic product, except perhaps provide confusion. As such, it is critical to recognize that the old rules still apply. Investigators using proteomic technology to identify biomarkers should clearly recognize the concept of design control in their experimental design to assure that there is an effective diagnostic resulting from the basic research. While new analytes, or biomarkers, are critical to address problems such as ovarian cancer, the use of the term biomarker does not endow the analyte with superior qualities.