Laboratory-Developed Tests in Molecular Diagnostics

Abstract

One of the fastest growing areas in clinical laboratory testing is molecular diagnostics. This growth has been in part the result of the tremendous amount of knowledge gained in the last decade from the Human Genome Project regarding organization, regulation, and expression of genomic information in humans and microbes. This knowledge has allowed us to better understand the pathogenesis of many diseases at the molecular level. As a consequence, diseases are being increasingly defined in terms of their molecular pathogenesis. This has lead to the development of new clinical molecular assays for diagnosis, prognosis, selection of therapeutic modalities, and monitoring of diseases. Until a few years ago, practical laboratory methods for detecting differences in nucleic acid sequences were not sufficiently simple or robust for the clinical laboratory. Recent advances in new technology, instrumentation, and efforts in standardization have overcome many of these limitations. The development and introduction of new technologies that allow automation of the testing process, as well as higher-throughput testing, have improved the diagnosis of diseases and patient care. In addition to the increasing number of kits and reagents used for molecular diagnostics approved by the Food and Drug Administration (FDA), a large number of molecular tests are still manufactured in-house by different clinical laboratories. In its role supporting US science and industry, the National Institute of Standards and Technology (NIST), a nonregulatory agency of the US Department of Commerce, provides physical and chemical standards in support of national commerce, manufacturing, and science (3). These materials are available internationally as Standard Reference Materials (SRMs) for use by industry developing assays and/or technology platforms for diagnostic use, by regulatory agencies ensuring the quality and efficacy of these assays, and by clinical laboratories providing diagnostic tests for patients. Traditionally, NIST responds to standard needs as defined by these communities. Consensus is developed through NIST workshops attended by representatives of these communities as well as direct request by other governmental agencies. Specific examples of ongoing programs within the Biotechnology Division at NIST are described in this chapter.