IOM Urges Coordinated Approach to Biomarker Discovery

WASHINGTON—Piecemeal and unorganized efforts have hindered research and development of cancer biomarkers, a new report by the Institute of Medicine (IOM) has concluded. The Institute urged federal agencies, other research sponsors, academic scientists, and private industry to unite behind 12 recommendations to create a coordinated, comprehensive approach to investigating, developing, and validating biomarkers that can aid in the early diagnosis of cancer or create optimal therapies for individual patients.

To deal with the current patchwork of standards for clinical use of cancer biomarkers and unclear regulatory authority over the field, the report recommended that federal agencies, particularly the National Cancer Institute, Food and Drug Administration, and National Institute of Standards and Technology, develop an "organized, comprehensive approach to biomarker discovery, and foster development of novel technologies."

"There is tremendous opportunity to improve the outcome for people with cancer by enhancing detection and treatment approaches. Biomarkers will be instrumental in making that transition," the IOM analysis emphasized. Its report, "Cancer Biomarkers: The Promise and Challenges of Improving Detection and Treatment," was prepared by an 11-person committee chaired by Harold L. Moses, MD, Hortense B. Ingram Professor of Molecular Oncology at Vanderbilt University School of Medicine.

The committee encouraged industry and other biomedical research funders to establish international public/private consortia, modeled after the Single Nucleotide Polymorphism Consortium, to generate and share methods and precompetitive data on the validation and qualifications of cancer biomarkers for specific uses.

Moreover, funding of research should emphasize development of quantifiable biomarkers of cell signaling pathways that will have the broadest uses, such as those applicable to different tumor types and drugs, as well as other diseases, the report said.

Further, federal agencies and other funders should sponsor adequately powered demonstration projects focused on a single disease or pathway to discover and develop biomarkers that can predict the safety and efficacy in individual patients of drugs already on the market. Such research would enable the identification of patient populations likely to respond to a drug, have resistance to a drug, or experience adverse reactions. NCI and other research sponsors should initiate and sustain funding for high-quality and highly accessible biorepositories of patient samples prospectively collected in conjunction with large cohort studies and clinical trials—and encourage their use for validating biomarkers.

Government agencies and other interested parties should also develop a transparent process to create well-defined consensus standards and guidelines for biomarker development, validation, qualification, and use.

The IOM urged the FDA and industry to work together to facilitate the co-development and approval of diagnostic-therapeutic combinations. It also encouraged FDA to more clearly delineate its expectations and requirements for these combinations, and to link approval of the therapeutic and diagnostic so that one is contingent upon the other. Companies need to better integrate basic and clinical research, the IOM added, and to emphasize the search for patient subpopulations based on theoretical and empirical evidence prior to phase III trials.

FDA also should clearly delineate and standardize its oversight of biomarker tests used in clinical decision-making and develop clear guidelines for this oversight. Either FDA or the Federal Trade Commission should monitor and enforce marketing claims made about molecular diagnostics, the committee emphasized.

Revise CMS Coding

The report further suggested that the Centers for Medicare & Medicaid Services (CMS) develop a specialty area for molecular diagnostics under the Clinical Laboratory Improvement Amendments, and revise and modernize its coding and pricing system for diagnostic tests.

IOM also recommended that CMS convene a meeting of interested parties to develop consensus guidance on how to assess diagnostics to make coverage and reimbursement decisions.

The report encouraged CMS and other payers to develop criteria for conditional coverage of new biomarker tests. Conditional coverage should include establishing procedures for high-quality, population-based assessments of the efficacy and cost-effectiveness of biomarker tests, the IOM said.