Laboratory Developed Tests: More Oversight, or More Vigilance and Reporting?

U.S. FDA Prepares to Oversee LDTs

Recently, the U.S. Food and Drug Administration’s Office of Public Health Strategy and Analysis issued an interesting (and much anticipated) report regarding Laboratory Developed Tests (LDTs). The Agency has consistently cited a need for greater oversight of LDTs out of concern for public safety.

Laboratory Developed Tests used to be simple tests designed by a local individual lab and used there for rare conditions. However now they have increased in sophistication and availability, and according to the American Clinical Laboratory Association, are frequently developed and used by hospitals, academic, and clinical laboratories.

As a leading developer of liquid chromatography and mass spectrometry (LC-MS) technologies often used by highly qualified, certified laboratories for their LDTs, Waters is vested in understanding this regulatory environment in partnership with our customers in clinical research and diagnostic laboratories around the world and the regulatory bodies themselves.

In the end, we are all working towards bringing safe and effective tests to patients for improved healthcare outcomes.

In brief, the report outlines 20 cases of “problematic” LDTs and their public health impact, as well as economic impact where data are available. The cases have been grouped by their primary problem (though some tests may suffer from more than one problem):

1. Tests that yield many false-positive results (i.e., the test result is positive when no disease/disorder is present); 3 of the 5 tests highlighted are biomarker assays for ovarian cancer
2. Tests that yield many false-negative results (i.e., the test result is negative when a disease/disorder truly is present)
3. Tests with the potential for both false-positive and false-negative results
4. Tests for which the factor has no clear relevance to the disease
5. Tests linked to treatments based on disproven scientific concepts
6. Tests that undermine drug approval or drug treatment selection
7. Other non-validated tests, including 25-hydroxyvitamin D by LC-MS

It is perhaps worth noting that some existing cleared/approved tests may also suffer from one or more of the above seven problems.

So perhaps the answer isn’t primarily or solely focused on greater pre-market notification or approval of LDTs? While the majority of the public discussion has centered on FDA’s proposed framework for LDT oversight, comparatively little focus has been placed on the perceived need for a vigilance system for post-implementation monitoring, such as is required for medical device manufacturers.

Just such a system is outlined in the second draft guidance issued by FDA on October 3^rd, 2014 – “FDA Notification and Medical Laboratory Developed Tests (LDTs)”. This guidance, if finalized, would create a system whereby manufacturers of LDTs would be required to, “identify and monitor significant adverse events involving medical devices [and report these events to FDA] so that problems may be detected and corrected in a timely manner.”

This topic will continue to be an interesting subject of much discussion as FDA finalizes its guidance for oversight of LDTs.

Additional resources:

• Waters capabilities: Better Results can Change the World
• At the Centre Hospital Universite de Sherbrooke (CHUS) in Quebec, metabolic disorders are found early to save newborns
• The ACLA’s opposition to FDA regulation of LDTs