Date:  March 23, 2012



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 or   A committee roster follows.


Additional Resources:

Report in Brief

Full Report

Project Website




Christine Stencel, Senior Media Relations Officer

Shaquanna Shields, Media Relations Assistant

Office of News and Public Information

202-334-2138; e-mail


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  Additional information is available at Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).

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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

Ann Arbor


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.

Clinical Director

Breast Oncology Program
Comprehensive Cancer Center

University of Michigan

Ann Arbor


Craig Henderson, M.D.

Adjunct Professor of Medicine
of Medicine

University of California

San Francisco


Larry Kessler, Sc.D.

Professor and Chair

Department of Health Services

School of Public Health and Community Medicine

University of Washington


Stanley Lapidus

Founder, President, and CEO
SynapDx Corp.

Southborough, Mass.


Debra Leonard, M.D., Ph.D.

Professor and Vice Chair of Laboratory Medicine, and

Director of Clinical Laboratories

Weill Medical College

Cornell University

New York City


Harold L. Moses, M.D.

Professor of Cancer Biology, Medicine, and

Pathology, and

Director Emeritus

Vanderbilt-Ingram Comprehensive

Cancer Center

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
Emory University



Nathan D. Price, Ph.D.

Associate Professor

Institute for Systems Biology



John Quackenbush, Ph.D.

Professor of Computational Biology and Bioinformatics

Dana-Farber Cancer Institute



Elda Railey

Research Advocacy Network

Plano, Texas


David Ransohoff, M.D.

Professor of Medicine and Epidemiology, and
Division of Digestive Diseases and Nutrition
University of North Carolina

Chapel Hill


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.

Study Director