A reality check for molecular diagnostics in clinical practice.

Molecular diagnostics, while still evolving, has had a major impact on the practice of laboratory medicine. Overall, the technologies that define molecular pathology as a discipline are universally applied to support clinicians in their healthcare delivery. The molecular pathology laboratory began with the transition of a few molecular biology research tools into the clinical laboratory to the more recent development of new technologies and instrumentation solely for clinical laboratory practice. Concomitantly, the demands for expanded applications to address diagnostic/prognostic, risk assessment, predisposition, and therapeutic testing have far outnumbered the capacity of laboratory delivery systems. As this discipline continues to mature, we must be willing to address issues pertaining to clinical utility, financial responsibility, advanced technologies, training and education. In light of the successes of the Human Genome Project and other genome projects, the number of potential nucleic acid targets for molecular diagnostics continues to increase. Given the current technologies, it is possible for a laboratory to develop ‘in-house’ or ‘laboratory developed’ assays on a routine basis for the purpose of diagnostic testing. In addition, industry is rapidly providing reagents under the analyte specific reagent (ASR) rule of the US Food & Drug Administration (FDA). The critical question is which of these nucleic acid targets will be most useful in patient care? In order for this discipline to move forward, we must better understand the clinical utility of tests offered in the laboratory. For example, most infectious diseases have been characterized by the fulfillment of Koch’s postulates which have most often associated a specific organism with a pathologic process. Therefore, identifying this organism in a patient specimen should indicate the presence of disease. However, molecular diagnostic testing has an unprecedented level of sensitivity and specificity. Latent or dormant infections, the presence of normal flora, and co-infections are all issues related to the clinical utility of a molecular microbiologic test. As another example, through genetic testing or genotyping, we are able to identify a gene target in a patient specimen. This qualitative type of data may not be sufficient without supportive clinical outcomes data. We must better understand mutation spectra, the penetrance of a specific mutation, the role of polymorphisms in normal and disease processes, as well as the association of haplotypes with disease processes. A laboratory test is only as meaningful as its interpretation. In this growing arena of molecular diagnostic tests, the paradigm has shifted from that of a technologic/scientific concern to one of a financial concern. Clearly, molecular diagnostic testing has proven itself. Yet, the addition of highly complex testing in conjunction with lack of replacement of traditional testing is viewed as an increase in laboratory costs. Keep in mind that under certain circumstances, an increase in laboratory cost may in fact result in decreased overall institutional healthcare costs. Reimbursement for molecular diagnostic testing varies considerably from state to state and is dependent upon payor mix and capitation rates.