By Karin Hoelzer, Director of Policy and Regulatory Affairs at the National Organization for Rare Disorders (NORD)
How should lab developed diagnostic tests (LDTs) be regulated? As the House Energy and Commerce (E&C) Health Subcommittee gathers this week to discuss this topic, rare disease patients, families and health care providers call for practical and feasible legislative solutions that are risk-based, data-driven, and that consider the unique challenges of LDTs for rare diseases. We urge Congress to find a compromise now that prevents bad tests from harming patients while ensuring continued access to diagnostic testing for rare disease patients – our patients and the future of rare disease therapies depend on it.
As the Health Subcommittee gathers this week to discuss this topic, we are all but certain to hear various diametrically opposed viewpoints with very little common ground – continuing a policy debate that has been ongoing for decades with very little tangible progress on how to best meet patient and health care provider needs for accurate and accessible diagnostic tools. Unfortunately, the delay in reaching agreement has diverted considerable resources and perpetuated substantial and inherently harmful uncertainty for rare disease patients that largely depend on LDTs.
The stakes are high for the roughly 1 in 10 Americans living with a rare disease. Here are the facts as they pertain to LDT use for rare diseases:
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- LDTs are central to the medical care of rare disease patients – and the economics of developing diagnostic tests for rare diseases are fundamentally different from other disease areas. As many as 80% of all rare diseases have a genetic component; many genetic tests in clinical use today are LDTs.[1] Similarly, most newborn screening tests administered by publicly funded and run newborn screening programs across the country are LDTs, as are many companion diagnostics such as biomarker tests central to the safe and effective use of many rare disease therapies, particularly in the oncology space.[2]
- Rare disease patients need and deserve accurate, reliable diagnostic tests and timely access to them. In many cases, an incorrect diagnostic test result can cause more harm for the patient and family than no diagnostic test at all. Yet, treatment delays also harm patients; many rare disease patients already face a long ‘diagnostic odyssey.’[3] Perhaps most importantly, an increasing number of innovative rare disease therapies have narrow treatment windows. Any delay in diagnosis can – and does – exclude rare disease patients from clinical trials, or from receiving FDA-approved therapies. Given the limited alternative treatment options for many rare diseases, such delays are often devastating for patients and families. Similarly, timely access to companion diagnostics such as biomarker tests,[4] which provide vital information about the safe and effective use of a corresponding drug or biologic, often determines if and when rare disease patients access life-altering therapies.
- Not all diagnostic tests are created equal or carry the same risks for patients. It is not feasible – or desirable – to require the same level of oversight over all tests regardless of how they are used or what risks and benefits they pose to patients. Companion diagnostics such as biomarker tests in particular play an increasingly important role in rare disease drug development, and delays in the approval or clearance of a companion diagnostic can lead to devastating delays in drug approval or biologic licensure.
- The existing regulatory framework for devices was not made for LDTs and will not work well for rare disease LDT; careful, deliberate implementation of any sweeping changes to the LDT sector is vital for success. Data on the use and performance of LDTs in rare diseases (and more broadly) to guide implementation are very scarce. This makes careful, deliberate implementation of any sweeping changes to the LDT sector particularly important. It also reinforces the need for ample input from ALL parts of the impacted communities.
The rare disease community needs Congress to come together in a bipartisan manner on this topic; we need legislative solutions that can adequately address the unique challenges and needs of all patients including the 30 million Americans living with rare diseases. Unfortunately, the upcoming hearing promises to be eerily similar to a hearing in the same subcommittee almost 10 years ago.[5]
- A key question this week – as 10 years ago – will likely be whether FDA should oversee LDTs at all, or whether they are better regulated by modernizing regulations under the Centers for Medicare and Medicaid Services (CMS) through the Clinical Laboratory Improvement Amendments (CLIA). FDA and CMS issued a joint statement in January of this year stating “[…] CMS does not have the expertise to assure that tests work” and “[…] the complementary FDA and CMS frameworks are both critical to assuring patients can rely on the clinical accuracy of their test results.”[6] Given CMS’s strong and recent view on the issue, further belaboring the point that FDA has the requisite expertise to provide oversight on LDTs this week will likely prove of limited utility.
- As in 2014, FDA sketched out a new proposal to regulate LDTs in fall of 2023 – the latest chapter in a long string of unsuccessful regulatory attempts dating all the way back to 2006.[7],[8],[9] When the public comment period closed last December, the agency had received more than 6,700 public comments, many expressing concerns about the proposed rule.[10] The resulting final rule is currently under Office of Management and Budget (OMB) review. NORD, as well as many other stakeholders, have serious concerns about the proposed rule and the potential unintended consequences associated with its practical implementation, similar to concerns NORD raised almost 10 years ago.[11],[12]
- The final rule is likely to raise many (or more) of the same concerns. Unfortunately, similar to 10 years ago, the forthcoming FDA regulatory proposal from FDA is unlikely to generate practical, tangible solutions.
So where does that leave the rare disease community? Representative Frank Pallone was right when he said during the hearing 10 years ago, “Presumably, all sides would agree that there should be enough oversight of tests to ensure that they are accurate and clinically relevant, but the oversight should not be so burdensome as to prevent or unnecessarily delay the development of important new tests or the improvement of existing tests. The difficulty, of course, is in achieving that balance.”[13]
Rare disease patients and families wholeheartedly agree – both then and now. We simply cannot continue this fruitless debate indefinitely. Rare disease patients, families and health care providers need practical and feasible solutions that are risk-based, data-driven, and that consider the unique challenges of LDTs for rare diseases. We urge Congress to come together in a bipartisan manner to find a compromise now that prevents bad tests from harming patients while ensuring continued access to diagnostic testing for rare disease patients – our patients and the future of rare disease therapies depends on it.
[1] Richardson, L., Dobias, M., Akkas, F., Younoszai, Z., & McAndrew, E. (n.d.). The Role of Lab-Developed Tests in then Vitro Diagnostics Market. The Pew Charitable Trusts. https://www.pewtrusts.org/-/media/assets/2021/10/understanding-the-role-of-lab-developed-tests-in-vitro-diagnostics.pdf
[2] Id.
[3] Barriers to Rare Disease Diagnosis, Care and Treatment in the US. (2020, November 19) National Organization for Rare Disorders.. https://rarediseases.org/wp-content/uploads/2020/11/NRD-2088-Barriers-30-Yr-Survey-Report_FNL-2.pdf
[4] Center for Devices and Radiological Health. Companion Diagnostics. (2023). U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/in-vitro-diagnostics/companion-diagnostics#:~:text=A%20companion%20diagnostic%20is%20a,corresponding%20drug%20or%20biological%20product.
[5] 21st Century Cures: Examining the Regulation of Laboratory-developed Tests. (2024, March 20). https://www.congress.gov/event/113th-congress/house-event/LC39273/text
[6] Center for Devices and Radiological Health. (2024, January 18). FDA and CMS: Americans Deserve Accurate and Reliable Diagnostic Tests, Wherever They Are Made. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/medical-devices-news-and-events/fda-and-cms-americans-deserve-accurate-and-reliable-diagnostic-tests-wherever-they-are-made
[7] Congressional Research Service. FDA Regulation of Laboratory-Developed tests (LDTs). (2022, December 7). https://crsreports.congress.gov/product/pdf/IF/IF11389
[8] Center for Biologics Evaluation and Research (CBER). Framework for Regulatory Oversight of Laboratory Developed Tests. (2014, October 3). U.S. Food and Drug Administration. https://www.fda.gov/media/89841/download
[9] Covington and Burling, LLP. HHS Issues New LDT Policy, Rescinding FDA Premarket Review Policies. (2020, August 25). https://www.cov.com/en/news-and-insights/insights/2020/08/hhs-issues-new-ldt-policy-rescinding-fda-premarket-review-policies
[10] Federal Register. Medical Devices; Laboratory Developed Tests. 88 FR 68006. (proposed 2023, October 03). https://www.federalregister.gov/documents/2023/10/03/2023-21662/medical-devices-laboratory-developed-tests
[11] NORD Supports Lifting the HDE Cap. National Organization for Rare Disorders. (2015, September 15). https://rarediseases.org/assets/files/policy-statements/2015-09-21.NORD-Supports-Lifting-the-HDE-Cap.pdf
[12] NORD Comments on Proposed LDT Rule. National Organization for Rare Disorders. (2023, December 04). https://rarediseases.org/wp-content/uploads/2023/12/NORD_comments_LDT_proposed_rule_2023_final.pdf
[13] 21st Century Cures: Examining the Regulation of Laboratory-Developed Tests. (2014, September 09). https://www.congress.gov/event/113th-congress/house-event/LC39273/text