About Critical Values

The U.S. Food and Drug Administration’s (FDA) proposed rule, granting itself regulatory authority over laboratory developed tests (LDTs), could impede hospitals and laboratories from providing lifesaving diagnostic care. The FDA maintains there is evidence to suggest some LDT tests are unreliable and produce erroneous results.  

The FDA’s proposed rule to regulate LDTs is a concern to the American Society for Clinical Pathology (ASCP) and other laboratory and pathology societies. The new rule is expected to be released soon, possibly by late April, which means laboratory developed tests will come under FDA authority.  

In its response to the FDA’s proposed rule, ASCP observed that the vast majority of LDTs are of excellent quality, though it acknowledged some have suffered from performance issues or were marketed inappropriately. ASCP also noted that some commercial, FDA-approved tests have suffered from performance issues. Matt Schulze, Senior Director of Public Policy for ASCP, says ASCP’s comments argued that the “FDA’s data gathering on LDTs appears to consist almost entirely of anecdotal reports, without systematic or scientific analysis of the problem.” 

Laboratory developed tests include diagnostic and screening tests developed by clinical laboratories, especially at large academic medical centers, often when commercially developed tests are not available. They are developed, validated for safety and effectiveness, and then performed in-house by individual laboratories. 

They range from routine tests to complex molecular and genetic tests for cancer, heart disease, and rare and infectious diseases. LDTs provide patients with access to accurate and high-quality testing for many conditions for which no commercial tests exist.  

“The overriding concern is that the regulation would interrupt the ability of hospitals and medical centers to develop and provide laboratory developed tests,” says Mr. Schulze. “In many situations, there are no alternative tests that can be used. There might be a reference laboratory that could perform the testing, but it might also be located far away. That delay could affect patient care.”  

The FDA historically has overseen manufacturers and devices under the Federal Food, Drug, and Cosmetic Act (FFDCA) to make certain that devices, including those used to diagnose disease, are safe and effective. In 1976, the Medical Device Amendments to the FFDCA were signed into law, enhancing FDA’s authority over medical devices and in vitro diagnostics (IVDs). Since that point, the Agency has focused on commercial diagnostics—testing equipment and related components and supplies that were sold by manufacturers.   

For LDTs, the Agency has generally exercised enforcement discretion, even though it continues to maintain that LDTs are devices and, therefore, subject to its oversight. Early on, LDTs were considered low risk, due to their small volume.   

Over time, however, LDTs began to proliferate. The Clinical Laboratory Improvement Act of (CLIA) 1988 was developed, under the oversight of the Centers for Medicare and Medicaid Services (CMS), to improve the standards within laboratories in order to improve testing quality. When CMS implemented its CLIA 1988 regulations, it established regulations governing LDTs.  

ASCP and other pathology and laboratory organizations maintain that the vast majority of LDTs are of excellent quality.  

So what happens when the proposed rule is approved? Many observers expect a lawsuit will be filed against the FDA, challenging its authority to implement the rule. Aside from a possible lawsuit, there is also legislation in Congress called the VALID Act, which also seeks to regulate LDTs and which many pathology and laboratory groups feel is less onerous. Consequently, if a lawsuit against the FDA’s proposed rule is unsuccessful, it will spur interest in the VALID Act. 

Ultimately, if the FDA’s proposed rule is finalized as is, Mr. Schulze says the FDA will likely implement the new rule in stages, one of which is that the FDA will require laboratories to submit their laboratory developed tests for review. “It will be an expensive process for the laboratory, and it will take the FDA a long time to review the tests,” Mr. Schulze says. 

The long-term outlook is less certain. Some laboratories may stop trying to develop their own tests or will stop trying to improve upon their existing LDTs. Others may cut back on developing LDTs. What is certain is that the new rule will have a big impact on laboratories and patient care.