TABLE 1.
Policy recommendations for strengthening U.S. Regulatory oversight of LDTs.
| Policy recommendation | Implementation strategy pros | Implementation strategy cons |
|---|---|---|
| Optimize FDA Enforcement Discretion | • Is a traditionally recommended approach | • High complexity tests are the most lucrative, which increases likelihood of misconduct, fraud, waste and abuse |
| • Well-funded large urban cities with improved access to high quality, safe LDTs, Companion Diagnostics (CDx) | • FDA addresses analytical and clinical validity in the pre-marketing clearance and approval process, and readily identifies fatal methodologic flaws which can be costly | |
| • Large academic medical centers and commercial laboratories have strong incentive for prioritizing omics LDT innovation d/t available grant, patent/intellectual property/legal infrastructure pipelines | • Costs favor large well-funded institutions that are administratively endowed for multi-sector expertise and the capacity to correctly respond to agency methodological concerns (i.e., Figure 1) | |
| • Is a profitable area of scientific research | • Smaller, less resourced hospitals, AMCs with high quality laboratory developed procedures (LDPs) under CLIA cannot easily add FDA regulatory requirements and keep costs manageable, will remove LDTs | |
| • FDA 510(k) and PMA IVD pipelines are well established and can be scaled up | • Proposed 4–5 years enforcement discretion phaseout is unrealistic for small, medium labs | |
| • FDA estimates $2.67–86.01 billion in savings over 20 years from direct health benefits from avoidance of faulty LDTs | • Increased likelihood of increased financial costs due to CMS health insurance claim rejection for NGS genetic/genomic tests, which requires additional patient payment assistance programs | |
| • Proposed rule includes transparent LDT adverse event reporting, correction and removal to monitor severe harms | • Small towns, middle, rural America would experience exacerbated resource gaps and U.S. healthcare disparities | |
| • Requires prospective data from clinical trials | • Costs, delays, LDT gaps would decrease capacity, inequity in key policy areas including maternal and perinatal healthcare, opioid abuse crises, and oncology and infectious disease | |
| • Increased likelihood of CMS financial reimbursement for medical devices, CDx and PGx drugs in Medicare payments | ||
| Modernize CLIA | • Focuses on assuring high quality laboratory processes, procedures for LDT use in clinical laboratories | • Evaluates LDT lab processes after they are in clinical use; may not always use informed consent |
| • Can add clinical validity for designated categories, and harmonize with FDA | • CMS has traditionally preferred FDA to handle clinical validity for LDT regulatory oversight | |
| • CMS’ CLIA is a preferred regulatory structure for ensuring flexibility for off-label applications in routine clinical settings | • Permissive and heterogeneous operating structure such that underqualified doctoral personnel (i.e., 1 year of lab experience) can easily set up their own LDTs without fully understanding the consequences of insufficient formal evaluation | |
| • Reimbursement and payment model is a more comfortable language compared to FDA for clinical providers | • Analytical validation limited to the conditions of the laboratory, staff, equipment, and patient populations | |
| • Endorsed by specialty laboratory professional groups and multi-sector stakeholders such as Association of Molecular Pathology (AMP), and the American College of Medical Genetics (ACMG) with a draft legislative proposal | • Requires a knowledgeable and qualified medical director to appropriately hire, direct the specialized staff for the complexity level, scope, coverage for the particular LDT or advanced technology involved | |
| • Additional requirements can be designed by the laboratory science community for current accreditation and proficiency testing structures that are harmonized with FDA. | • Increased costs of proficiency testing, accreditation requirements will decrease LDT availability and impact patient operations | |
| • Can add regional peer review mechanisms for high-complexity laboratory directors to strengthen or stratify specific regulatory layers by LDT technology or method (i.e., oncology [liquid biopsies], NGS, qPCR, MALDI-TOF, LC-MS/MS assay, prenatal testing, AI/ML, etc.) | • If no CMS benchmarks, need a method for reporting LDT-related adverse events for safety and quality monitoring transparency | |
| • Can link to CMS benchmarks for improved laboratory accountability | • Medicare/Medicaid (CMS) fraud, waste and abuse is a persistent challenge, especially in emerging scientific innovation areas of great need (i.e., COVID-19) | |
| Maintain Status Quo | • Allows industry to self-regulate within their preferred and current cost, operational and regulatory resource constraints | • Range of LDT complexity and no formal mechanism to track genomic testing numbers, complexity, types of testing services, means it will not be possible to understand the worst healthcare disparities, patient and family harms |
| • FDA’s voluntary CDx pilot program offers co-development of oncology drug products with certain types of LDTs (NGS, PCR, FISH, IHC) linked to an IVD structure | • Continued lack of transparency for the most egregious harms, due to no requirements for publicly reporting LDT-related adverse events to some sort of central authority | |
| • Can revise current databases such as FDA-CLIA, FDA Manufacturer and User Facility Device Experience (MAUDE), FDA Medical Device Recalls for strengthened adverse event measures and data visualization | • Large-scale LDT modifications for tests with complex components in CLIA labs, followed by promotional marketing as FDA-alternatives, are not easily distinguishable from truly FDA-vetted tests | |
| • Optimize NCBI Genetic Testing Registry, for additional voluntary self-submitted information about relevant LDT safety, quality, adverse events, AI/ML and clinical decision support system use, FDA review and CLIA certification status components | • Fragmented, non-harmonized regulatory frameworks means continued litigation for patient harms and medication, diagnostic errors | |
| • Permissive regulatory environment of FDA enforcement discretion means most LDTs are unregulated and maximally favoring local autonomy and finance models | • No informed consent, adverse reporting, clinical validity in CMS CLIA | |
| • CMS-CLIA certification for high complexity laboratories can provide LDT informed consent if using DHHS Common Rule before the tests are used on patients | • CMS CLIA surveys indicate significant laboratory challenges, deficiencies in workforce qualifications and non-compliance with manufacturer instructions | |
| • Consider development and addition of LDT error rates, never events, adverse events to AHRQ Quality and Patient Safety Indicators | • Anticipate continued independent journalism analyses of corporate scandals, LDT failures, health care quality, patient safety issues and implications (i.e., COVID-19), followed by media and policy stakeholder scrutiny and agency accountability | |
| • Older adults and vulnerable, underserved populations are especially susceptible to genetic/genomic testing fraud, misuse and abuse schemes linked to illegal kickbacks, particularly in the areas of prenatal screening and cancer screening, diagnosis, treatment | ||
| • Can have adverse impacts on the level of public trust in U.S. science, public health and healthcare infrastructure |