Twelve Thousand Tests, Zero Oversight

Laboratory developed tests (LDTs) — in vitro diagnostic tests designed, manufactured, and used within a single laboratory — are exempt from FDA premarket review under longstanding enforcement discretion. Unlike commercial in vitro diagnostics (IVDs), LDTs do not undergo FDA analytical and clinical validation, performance testing, or adverse event reporting. This creates a regulatory gap in which tests with widely varying accuracy are used for critical clinical decisions including cancer diagnosis, pharmacogenomics, prenatal screening, and infectious disease detection. The FDA's 2024 attempt to close this gap through rulemaking was struck down in court and subsequently rescinded, leaving an estimated 12,000+ LDTs on the market with no federal analytical performance oversight.

An estimated 12,000+ LDTs are in use across U.S. laboratories, including tests for cancer biomarkers, rare diseases, pharmacogenomics, and prenatal screening. Inaccurate test results can lead to misdiagnosis, inappropriate treatment, unnecessary surgical procedures, or missed diagnoses of treatable conditions. The direct-to-consumer genetic testing market, which relies on some LDT methodologies, reaches millions of consumers. Quality failures in LDTs have been documented in high-profile cases (Theranos) and in numerous less-publicized cases of variable next-generation sequencing panel performance, where the same patient sample can yield different results depending on the laboratory.

The FDA issued a final rule in May 2024 establishing a phaseout of enforcement discretion for LDTs, classifying them as IVDs subject to premarket review. A federal district court vacated the rule in March 2025, finding the FDA exceeded its statutory authority, and the FDA formally rescinded it in September 2025, restoring the regulatory gap. Multiple legislative proposals — most notably the VALID Act — have attempted to create a new regulatory framework for LDTs, but none have been enacted due to opposition from laboratory industry stakeholders, academic medical centers, and concerns about regulatory burden on small laboratories. LDTs are subject to CLIA (Clinical Laboratory Improvement Amendments) oversight, which addresses laboratory quality systems and personnel qualifications but was never designed to evaluate the analytical or clinical validity of specific tests. Proficiency testing programs for LDTs are inconsistent and limited in scope. In genomics and next-generation sequencing, validation methods vary, reporting standards differ, and interpretation frameworks diverge across laboratories.

Congressional legislation creating a tailored regulatory framework for LDTs — distinct from the traditional IVD pathway but requiring analytical validation and adverse event reporting — would directly address the statutory authority gap that doomed the FDA's rulemaking approach. Alternatively, a voluntary accreditation program with transparent performance benchmarking (analogous to how CAP accreditation works for laboratories) that publicly reports LDT-level analytical validity data could create market-driven quality pressure. Standardized reference materials and proficiency testing panels for high-complexity LDTs (especially NGS-based tests) would enable meaningful quality comparisons even without new regulation.

A student team could design a standardized benchmarking framework for a specific category of LDTs (e.g., oncology NGS panels) using publicly available reference samples and variant databases (e.g., Genome in a Bottle, ClinVar) to quantify inter-laboratory variability. Another entry point would be developing a transparency platform that aggregates and displays publicly available LDT performance data, helping clinicians and patients understand the evidence behind the tests they rely on. Teams with backgrounds in genomics, laboratory science, data science, or health policy would be well-suited. A scoped semester project could focus on a single test category and a handful of public proficiency testing datasets.