The Science of "Omics:" Regulating Bioinformatic Tests in Medicine

The rapid development of new genetic tests and the expansion of commercial genetic testing reflect the years of molecular research that has uncovered genes, proteins, RNA and metabolites that are implicated in disease processes.  Widely known are, for example, the single gene tests that allow a patient to be tested for a genetic predisposition to disease based on whether she has a mutation in the relevant gene (e.g., BRCA1 testing for breast/ovarian cancer).  But these conceptually simply tests are rapidly being supplemented by the next wave of clinical molecular medicine. The collection of fields now known collectively as “omics” represent molecular science as it now seeks to explain biological phenomena through the collective behavior of multiple genes or proteins (essentially looking for patterns in large datasets). These become the fields of genomics, proteomics, metabolomics, etc. Because of the large data volumes, they lie at the intersection of biotechnology and computer science (i.e., bioinformatics). One commercially available example is the Mammaprint genetic test, which tests 70 genes in a breast cancer patient genes to develop a genetic “signature” that indicates the likelihood of recurrence (and the advisability of further treatment). Such a test requires the collection of accurate biological data accompanied by a computational model that integrates the profile information to arrive at a clinically relevant conclusion. Some of these tests to date have been regulated by the Food and Drug Administration as in vitro diagnostics (IVD), but there is no coherent regulatory scheme for genetic laboratory science that integrates the oversight of single-gene genetic tests with the more complex genetic signature tests. However, due to a recent case at Duke University where a researcher had engaged in the use of faulty gene pattern tests as the basis for decision-making in providing chemotherapy to cancer patients in clinical trials, the National Cancer Institute asked the Institute of Medicine (IOM) to review how “omics” tests are developed, validated and regulated. In the report recently issued, Evolution of Translational Omics: Lessons Learned and the Path Forward, the IOM has called for improvements in the way these "omics" tests are peer-evaluated, but also asks for the developers of such genetic tests to consult with the FDA prior to using such tests in clinical trials.These developments are very significant because we expect that the potential uses of molecular patterns to inform clinical decisions are numerous but potentially susceptible to irregular development and even (unintentional) misuse. The uneven involvement of the FDA in the regulation of genetic testing has contributed to the chaotic environment in which these technologies are entering clinical trials, and later, the marketplace. The real world consequence is that patients could be given faulty clinical information regarding their diagnosis, prognosis or treatment options. While the incentives to produce gene or protein signatures of clinical significance will increase, the consequences of misinformed clinical care are very real. A the IOM report concludes, all of this argues for a institutional culture – government, funders, universities, journals – that appreciate the novel, interdisciplinary nature of these laboratory tests and provide assessments that match their complexity.