The Institute of Medicine (IOM) committee’s statement of task refers to three trials that were conducted at Duke University. Table B-1 outlines some information related to those trials.
This appendix provides a concise summary of the research objectives and the approaches taken in developing several of the gene expression– based chemosensitivity tests implemented in the three clinical trials in Table B-1, and presents findings that provide important insights about processes that were in place at Duke University, to enlighten the development of and to provide motivation for many of the IOM committee’s recommendations that are intended to enhance the integrity of future omics-related research. Many of these findings are in key areas that include the responsibilities of investigators and institutions, conflict of interest issues, and the roles of funders, regulatory authorities, journals, and biostatistical collaborators.
DEVELOPMENT AND EVALUATION PROCESS
Investigators are responsible for systematic and rigorous development of omics-based tests. Chapters 2, 3, and 4 explain the IOM committee’s recommendations on omics-based test discovery, development, and evaluation for clinical use. These recommendations are meant to help establish a process, agreed on by all collaborating disciplines, for the discovery and development of omics-based tests with the goal of improving patient care and outcomes.
Discovery and Test Validation Phases
Chapter 2 explains the technologies, statistical methods, computational methods, and bioinformatics methods that should be used in the discovery and confirmation of omics-based tests. Recommendation 1 defines critical steps in the discovery and confirmation of new candidate omics-based tests. Recommendation 2 (Chapter 3) focuses on omics-based test development and validation within a clinical laboratory certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), in preparation for use in patient management decisions in clinical trials or for eventual use in patient management decisions in medical care. These steps include the design, optimization, validation, and implementation of the locked-down test in single or multiple CLIA-certified laboratories. Recommendation 2 also emphasizes discussion of a candidate test with the Food and Drug Administration (FDA) prior to validation.
The sections below present facts from the discovery and validation phases of the gene expression–based tests developed at Duke University and used in the three clinical trials the committee was tasked to evaluate: