Concerns, Support Weighed for FDA’s Proposed Regulation of Laboratory Developed Tests

Energetic debate surrounding the U.S. Food and Drug Administration’s (FDA) proposed regulatory framework for oversight of laboratory developed tests (LDTs) is coming to a head in the cancer research community. The official comment period on the FDA’s proposed guidance ended in early February, while the House Energy and Commerce Committee’s 21st Century Cures initiative discussion draft, released in late January, includes a placeholder for LDT language.

2014-10_lab Although a number of organizations have taken formal positions on the matter, the Association of American Cancer Institutes (AACI) continues to weigh the pros and cons and gather input from its members. Two AACI cancer centers—Memorial Sloan Kettering Cancer Center (MSK) and the Mayo Clinic—have publicly filed their reactions. If your institution has submitted comments to the FDA or the House Energy and Commerce Committee on the draft LDT guidance, please share your comments with AACI Government Relations Manager Jennifer W. Pegher,

In a letter to FDA Commissioner Dr. Margaret A. Hamburg, MSK’s David S. Klimstra, MD, and Marc Ladanyi, MD, expressed concerns about patient access to tests, innovation, and duplicative regulation:

“We support a thoughtful, phased-in approach to regulation of the highest risk LDTs, but urge the FDA to revise the draft framework to better safeguard both innovation and patients’ access to the LDTs developed in academic non-profit clinical laboratories that have been such a key element of recent advances in precision medicine for cancer patients. As currently written, MSK anticipates that a significant proportion of the LDTs offered by our Molecular Diagnostics service could be subject to premarket review requirements.”

Drs. Klimstra and Ladanyi made seven recommendations, including that FDA should:

  • Better define the term “LDT”
  • Clarify that a panel test will be treated as one LDT under the new framework
  • Clarify both the standard for and objective of demonstrating clinical validity for intended use for LDTs that are not subject to continuing enforcement discretion under this framework
  • Maximize reliance on existing evidence, consensus statements, clinical practice guidelines, and third-party review for LDTs subject to pre-market review

In a statement submitted to the U.S. House of Representatives Committee on Energy and Commerce Subcommittee on Health, Mayo Clinic’s Department of Laboratory Medicine and Pathology rejected FDA’s plan in favor of updated CLIA regulations.

Commenting on the section of the 21st Century Cures legislation headed, “A Modernized Framework for Innovative Diagnostic Tests”, Mayo wrote:

“[A]dditional layers of regulatory structure, including FDA approval, are not the answer to perceived problems with LDTs. We believe that the appropriate response is to update CLIA and add necessary requirements such as clinical validity, adverse event reporting, quality systems, post-market surveillance, etc. The 21st century modernization of the regulatory framework for LDTs needs to occur through updates to CLIA regulations rather than through additional FDA regulation of LDTs.”

Last fall, the American Association for Cancer Research (AACR) issued a statement supporting FDA regulation of molecular diagnostic tests, especially tests used to make high-risk treatment decisions, arguing that it will ensure patient safety while promoting medical product innovation.

AACR also made the following recommendations:

  1. Ensuring the safety, reliability and accuracy of diagnostic tests is vital to safeguard patients, advanced personalized medicine and promote innovation.
  2. Implementing a single, strict regulatory pathway through the FDA will help reassure clinicians, patients and the public that the tests used to make treatment decisions are safe, accurate and effective.
  3. Having a predictable and reliable regulatory environment is important to encourage an innovative biomedical ecosystem in the United States.

AACI hopes that the ongoing debate will lead to a regulatory policy that encourages and supports the innovation that is taking place at the nation’s cancer centers related to LDTs, while also assuring that patients are protected from premature incorporation of such testing in non-research settings.

Fresh Faces on House Subcommittee Offer Potential for Improved Appropriations Process

Earlier this week, the House Appropriations Subcommittee on Labor, Health and Human Services (HHS), Education, and Related Agencies held the first hearing of the year on the National Institutes of Health (NIH) fiscal year (FY) 2016 budget request.


NIH Director Dr. Francis Collins

Panelists included NIH director, Dr. Francis Collins, Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases, Dr. Gary Gibbons of the National Heart, Lung and Blood Institute, Dr. Tom Insel of the National Institute of Mental Health, and Dr. Nora Volkow of the National Institute on Drug Abuse.

In his remarks, Dr. Collins noted that the NIH has worked diligently to enhance human health, lengthen life, and reduce illness and disability. He acknowledged that the leadership, employees, and grantees passionately believe in the NIH’s mission. He said that the foundation of basic science has driven NIH’s ability to understand disease for more than a century through diagnosis, treatment and prevention.

Dr. Collins stressed the NIH’s intent to lead the charge on the recently unveiled Precision Medicine Initiative (PMI). He reminded the subcommittee that the near term goal of the PMI focuses on cancer and added that cancer research has been leading the way in precision medicine for many years, by defining the driver mutations in individual tumors and using this information to design ideal therapies for each patient. He said the PMI seeks to accelerate discovery and expand current cancer genomics research to understand the development of resistance to targeted therapy, to apply non-invasive methods to track patients’ responses to treatment, and to explore the efficacy of new drug combinations targeted to specific tumor mutations. Highlighting a young woman’s epidermal growth factor receptor (EGFR) mutation and her positive response to the drug Tarceva, Dr. Collins said the PMI would allow researchers to do groundbreaking, historic work.

Dr. Collins noted that the President’s FY 2016 budget request for the NIH is $31.311 billion ($1 billion above the enacted FY 2015 level). Supporting the president’s request would allow 10,303 new and competing Research Project Grants (RPGs) to be funded in FY 2016, an increase above FY 2015 grant levels. The budget would also provide the capacity to improve the health of our nation and the ability to maintain the U.S.’ standing in biomedical science and develop new therapies, he said.

Reminding the subcommittee that China is now filing more patents in medicine than the U.S., Dr. Collins said that we are in danger of relinquishing our standing in biomedical research. While the subcommittee’s Ranking Member Rosa DeLauro (D-CT) recommended doubling the NIH budget, Dr. Collins suggested the best thing for the NIH would be a budget that is on stable growth trajectory and that keeps pace with inflation, plus a little bit more, which would allow the U.S. to flex its innovative muscles.

Chairman Tom Cole (R-OK) communicated his commitment to making NIH funding a priority for the subcommittee and offered to do what he can to support the NIH, despite funding restrictions imposed by budget caps.

Jennifer W. Pegher, AACI Government Relations Manager