The National Academies Press

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1 Introduction
Pages 17-32

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From page 17... ... By measuring, in each patient sample, thousands of genetic variations, mutations, or changes in gene and protein expression and activity, scientists are identifying previously unknown, molecularly defined disease states and searching for complex biomarkers that predict responses to therapy and disease outcome. This new understanding is beginning to shape both the ways in which diseases are managed and how new drugs and tests are being developed and used. Read the entire page →
From page 18... ... Recently, the scientific community raised serious concerns about several omics-based tests developed to predict sensitivity to chemotherapeutic agents, developed by investigators at Duke University. The initial papers describing these omics-based tests garnered extensive attention because results suggested a potential major advance in the discovery and use of omics-based tests to direct choice of therapy for individual cancer patients. Read the entire page →
From page 19... ... Dr. Varmus asked the IOM to conduct an independent analysis of the omics-based tests developed at Duke and define evaluation criteria for ensuring high standards of evidence for the development of omics-based tests prior to their use in clinical trials. Read the entire page →
From page 20... ... Department of Veterans Affairs, the American Society for Clinical Pathology, and the College of American Pathologists, an IOM committee was charged to identify appropriate evaluation criteria for developing clinically applicable omics-based tests and to recommend an evaluation process for determining when predictive tests using omics-based technologies are fit for use in clinical trials, especially those in which the assay is used to direct patient care (Box 1-1) Read the entire page →
From page 21... ... The process of taking an omics-based test into clinical trials to evaluate a test for clinical utility and use is described, but no recommendation is made on how, finally, to take a test from the clinical trial setting into clinical practice. However, discussion of this step is critical for understanding the recommendations of the committee because this step may involve using an omics-based test to direct patient management in clinical trials, which is within the charge of the committee. Read the entire page →
From page 22... ... Effect Modifier: A measure that identifies patients most likely to be sensitive or resistant to a specific treatment regimen or agent. An effect modifier is particularly useful when that measure can be used to identify the subgroup of patients for whom treatment will have a clinically meaningfully favorable benefit-to-risk profile. Read the entire page →
From page 23... ... Ideally, this involves assuring that the test can accu rately predict the clinical outcome of interest in an independent set of samples that were not used in developing the test. Such validation is particularly important as omics tests typically involve computational models whose parameters can be over fit in any single dataset, leading to an overly optimistic sense of the test's accuracy. Read the entire page →
From page 24... ... . Uses intended for clinical practice include risk assessment, screening, diagnosis, prognosis, prediction of response to therapy (effect modifiers) Read the entire page →
From page 25... ... tive or resistant to a specific treatment regimen or agent. Effect modifiers are particularly useful when they can be used to identify the subgroup of patients for whom treatment will have a clinically meaningful favorable benefit-to-risk profile. Read the entire page →
From page 26... ... More detailed descriptions of biomarker types and examples, as well as the types of clinical studies and trials in which biomarkers are developed, are given in Appendix C Evaluation of Biomarkers and Surrogate Endpoints As outlined in the statement of task, this committee was charged with identifying appropriate evaluation criteria for tests based on omics technologies, including criteria for the analytical validation, qualification, and Read the entire page →
From page 27... ... . The 2010 committee recommended a three-step biomarker evaluation framework consisting of analytical validation, qualification, and utilization, and intended the framework to be applicable to a diverse range of biomarker uses, including panels of biomarkers. Read the entire page →
From page 28... ... Because the regulatory and oversight requirements for clinical laboratory tests are both different and less clear than for drugs, a greater burden is placed on the institutions to oversee biomarker-based test research and development. While pharmaceutical companies follow well-established drug development pathways and have many process controls in place for strong oversight of drug development and manufacturing, academic institutions are not as accustomed to overseeing the development of medical products. Read the entire page →
From page 29... ... These responsible parties include the biomedical and clinical research community, investigators, institutions -- public and private, commercial and nonprofit -- funders of omics research, and journals that publish the results of omics research and clinical trials. Finally, the general public, as potential clinical trial participants and the beneficiaries of the products developed through this research, also may be interested. Read the entire page →
From page 30... ... Chapter 3 describes the processes for defining the clinical test method and for assessing analytical and clinical/biological validation prior to use of an omics-based test in a clinical trial to evaluate the clinical utility and use of the test. Chapter 4 describes the process for assessing the clinical utility and use of a new omics-based test. Read the entire page →
From page 31... ... 2010. NCI Address to the Institute of Medicine Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials. Read the entire page →

From page 17...

... By measuring, in each patient sample, thousands of genetic variations, mutations, or changes in gene and protein expression and activity, scientists are identifying previously unknown, molecularly defined disease states and searching for complex biomarkers that predict responses to therapy and disease outcome. This new understanding is beginning to shape both the ways in which diseases are managed and how new drugs and tests are being developed and used.

1 Introduction Pages 17-32

1 Introduction
Pages 17-32