Date: March 23, 2012
FOR IMMEDIATE RELEASE
IOM Report Recommends Evaluation and Validation Process to Prevent Problems Associated With Turning 'Omics' Research Into Clinical Tests
WASHINGTON — Genomics, proteomics, and other branches of molecular bioscience offer the prospect of greater precision in medical care, but some clinical tests based on "omics" research have proved invalid and highlighted the challenges of dealing with complex data. To enhance the translation of omics-based discoveries to clinical use, a new report by the Institute of Medicine recommends a detailed process to evaluate whether the data and computational steps underlying such tests are sound and the tests are ready to be used in clinical trials. The proposed process defines responsibilities and best practices for the investigators, research institutions, funders, regulators, and journals involved in development and dissemination of clinical omics-based technologies.
The request for the IOM report stemmed in part from a series of events at Duke University in which researchers claimed that their genomics-based tests were reliable predictors of which chemotherapy would be most effective for specific cancer patients. Failure by many parties to detect or act on problems with key data and computational methods underlying the tests led to the inappropriate enrollment of patients in clinical trials, premature launch of companies, and retraction of dozens of research papers. Five years after they were first made public, the tests were acknowledged to be invalid.
Lack of clearly defined development and evaluation processes has caused several problems, noted the committee that wrote the report. Omics-based tests involve large data sets and complex algorithms, and investigators do not routinely make their data and computational procedures accessible to others who could independently verify them. The regulatory steps that investigators and research institutions should follow may be ignored or misunderstood. As a result, flaws and missteps can go unchecked.
Investigators should be required to make the data, computer codes, and computational procedures used to develop their tests publicly accessible for independent review and ensure that their data and steps are presented comprehensibly, the report says. Agencies and companies that fund omics research should require this disclosure and support the cost of independently managed databases to hold the information. Journals also should require researchers to disclose their data and codes at the time of a paper's submission. The computational procedures of candidate tests should be recorded and "locked down" before the start of analytical validation studies designed to assess their accuracy, the report adds.
It is not always clear when researchers and institutions are legally required to consult with the U.S. Food and Drug Administration about new tests developed in clinical laboratories, such as omics-based tests. The committee therefore urged researchers and institutional officials to discuss newly created tests and their intended uses with the agency as a matter of course prior to the start of validation studies. In turn, FDA should issue either guidance or a regulation that specifies when developers need to submit omics-based tests to the agency for review, the report says. Tests should not be changed during clinical trials without a protocol amendment and further discussion with FDA.
Lack of clarity about the regulatory framework for laboratory-developed tests means academic medical centers can choose to move new omics-based tests from discovery to clinical use without external review. This places new, mostly unrecognized responsibilities on these institutions to provide proper oversight of the process.
Given the lessons from the Duke cases and the complexity of these new technologies, institutional leaders should pay greater attention to promoting a culture of scientific integrity and transparency, the committee said. Institutions should establish means to prevent, report, and investigate lapses in scientific integrity. They should designate institutional officials to assess and manage potential conflicts of interest among individuals and the institution, and should supervise procedures for responding to scientific questions or criticisms. They also should ensure that the many scientific disciplines involved in omics research are represented on oversight bodies.
Funders and journals share responsibility for identifying potential problems and responding to questions about the integrity of omics research and development, the committee said. Federal funders, such as the National Institutes of Health, should have the authority to investigate the work of researchers they are supporting even if the study or clinical trial is funded by others. Journal editors should make a greater effort to resolve alleged errors or data corruption in published papers.
"We hope that this report will help all members of the investigative team understand the entire pathway of translating omics discoveries into clinical tests and recognize and avoid the potential pitfalls at each stage," said committee chair Gilbert Omenn, professor of internal medicine, human genetics, and public health, and director, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor. "We believe that past problems, such as the Duke case, could have been prevented had a clearly defined process been available and been utilized. Scientific and clinical progress in omics test development will be accelerated if these recommendations are broadly adopted."
The report was sponsored by the National Cancer Institute, U.S. Food and Drug Administration, U.S. Department of Veterans Affairs, Centers for Disease Control and Prevention, American Society for Clinical Pathology, and College of American Pathologists. Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides objective, evidence-based advice to policymakers, health professionals, the private sector, and the public. The Institute of Medicine, National Academy of Sciences, National Academy of Engineering, and National Research Council together make up the independent, nonprofit National Academies. For more information, visit http://national-academies.org or http://iom.edu. A committee roster follows.
Report in Brief
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Copies of Evolution of Translational Omics: Lessons Learned and the Path Forward are available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at http://www.nap.edu. Additional information is available at http://www.iom.edu/translationalomics. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).
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INSTITUTE OF MEDICINE
Board on Health Care Services
Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials
Gilbert S. Omenn, M.D., Ph.D. (chair)
Professor of Medicine, Genetics, and Public Health
Center for Computational Medicine and Bioinformatics
University of Michigan Medical School
Catherine D. DeAngelis, M.D., M.P.H.
Johns Hopkins School of Medicine and Bloomberg School of Public Health, and
Editor in Chief Emerita
Journal of the American Medical Association
David L. DeMets, Ph.D.
Professor of Statistics and Biostatistics, and
Department of Biostatistics and Medical Informatic
University of Wisconsin
Thomas R. Fleming, Ph.D.
Professor of Biostatistics and Statistics
University of Washington
Gail Geller, Sc.D., M.H.S.
Johns Hopkins University
Joe Gray, Ph.D.
Gordon Moore Endowed Chairman;
Center for Spatial Systems Biomedicine; and
Associate Director for Translational Research
Knight Cancer Institute
Oregon Health and Science University
Daniel F. Hayes, M.D.
Breast Oncology Program
Comprehensive Cancer Center
University of Michigan
Craig Henderson, M.D.
Adjunct Professor of Medicine
School of Medicine
University of California
Larry Kessler, Sc.D.
Professor and Chair
Department of Health Services
School of Public Health and Community Medicine
University of Washington
Founder, President, and CEO
Debra Leonard, M.D., Ph.D.
Professor and Vice Chair of Laboratory Medicine, and
Director of Clinical Laboratories
Weill Medical College
New York City
Harold L. Moses, M.D.
Professor of Cancer Biology, Medicine, and
Vanderbilt University Medical Center
William Pao, M.D., Ph.D.
Associate Professor of Medicine
Ingram Association of Cancer Research, and
Personalized Cancer Medicine
Vanderbilt University School of Medicine
Rebecca D. Pentz, Ph.D.
Professor of Hematology and Oncology
Winship Cancer Institute
Nathan D. Price, Ph.D.
Institute for Systems Biology
John Quackenbush, Ph.D.
Professor of Computational Biology and Bioinformatics
Dana-Farber Cancer Institute
Research Advocacy Network
David Ransohoff, M.D.
Professor of Medicine and Epidemiology, and
Division of Digestive Diseases and Nutrition
University of North Carolina
E. Albert Reece, M.D., Ph.D., M.B.A
Vice President for Medical Affairs, and
Bowers Distinguished Professor and Dean
School of Medicine
University of Maryland
Daniela M. Witten, Ph.D.
Assistant Professor of Biostatistics
University of Washington
Sharyl Nass, Ph.D.