What the U.S. Government Thinks Is a Priority for Personalized Medicine to Happen

These are excerpts from http://www.ostp.gov/galleries/PCAST/pcast_report_v2.pdf.

• “The Federal government should make critical investments in the enabling tools and resources essential to moving beyond genomic discoveries to personalized medicineproducts and services of patient and public benefit.”
• “FDA should implement a more transparent, systematic, and iterative approach to the regulation of genomics-based molecular diagnostics.”

“Molecular diagnostics can be used in a variety of ways to inform personalized medicine

• Assess the likely efficacy of specific therapeutic agents in specific patients.
• Identify patients who may suffer disproportionately severe adverse effects from a given treatment
  or dosage.
• Determine optimal dosages for drugs whose therapeutic effect is known to vary widely.
• Assess the extent or progression of disease – Molecular diagnostics have the potential to provide more accurate and timely information on disease prognosis or treatment effectiveness than the imaging and pathology methods currently used for this purpose, though future diagnostic approaches may integrate all of these methods.
• Examine surrogate measures for clinical outcomes – Researchers are investigating whether  biomarker-based molecular diagnostics can provide reliable proxies for longterm outcomes such as relapse or survival. Such tests could be used to shorten the length and expense of clinical trials.
• Identify patients who can benefit from specific preventive measures

Clinical Decision Support

• To date, few genomics-based diagnostic tests have reached the market, and these few products have been targeted primarily at clinical specialists and subspecialists who have been able to assimilate them into practice without special measures. However, if the number of innovative personalized medicine diagnostics and linked diagnostic therapeutic combinations reaching the market increases substantially, widespread adoption of these products

Molecular Diagnostics

• The ability to generate genetic profiles using microarrays and sequence-based approaches promises to expand greatly the utility of genetic tests in clinical medicine. This is because human diseases resulting from a single genetic alteration are rare. Most common diseases including cancer, cardiovascular disease, and diabetes result from a variety of genetic changes acting in concert. Moreover, the exact combination of genetic factors resulting in a specific disease often varies among individuals. To address this complexity, many companies and academic groups are developing complex molecular diagnostics (including IVDMIA tests based on microarrays) with the goal of establishing correlations between a specific pattern of genetic modification and/or gene expression and disease outcomes such as progression, response to therapy, or adverse reactions. In some cases, these correlations and their predictive value are strong enough that the tests can have clinical utility even in the absence of a full understanding of the effects of and interactions among the component genes. As with genome-wide association studies, there are many pitfalls in establishing robust and reliable disease correlations for genomic profiling tests.46, 47 Reproducible sample collection and processing is essential to avoid artifacts in gene expression patterns due to cell population subtypes or effects of processing on the apparent levels of expression. Standards for the measurement, analysis, and reporting of biomarker data are essential to allow data to be compared across different studies and different laboratories and reduce duplication in defining assay methods and data requirements. Complicated statistical methodologies are required because probing the expression of 10,000 or more genes can lead to spurious correlations simply by chance. Moreover, these studies require not only large sample sizes but also validation using independent sample sets.