In this series of posts on Laboratory Developed Tests (LDTs), I discuss the history of the regulation of LDTs and impending changes (posts #1 and #2).  I also discuss possible criteria that pathologists, treating physicians, and healthcare systems could use to determine which tests are well validated (post #3).

I think there are at least four reasons for pathologists to learn more about LDTs right now:  1) the number of LDTs, particularly in oncology, is rapidly increasing, 2) the demands for fresh and fixed tumor tissue for reserch and biorepositories are also rapidly increasing, 3) some of these assays are associated with significant costs (thousands of dollars per test in many instances), 4) the regulatory oversight of LDTs is undergoing a major change.

Laboratoty Developed Tets (LDTs) are tests that are developed, validated, and performed in only one laboratory.  Unlike most tests, LDTs are not sold or distributed to other commercial or hospital-based laboratories. Many of these tests are complex genetic assays, some of which involve analyzing the expression of multiple genes to generate a predictive or prognostic index for a type of cancer or to help determine the site of origin for a metastatic tumor.  The tests that analyze multiple genes or evaluate combinations of results were formerly referred to as In Vitro Diagnostic Multivariate Index Assays (IVDMIA) (more on this in the next post). A gene expression profiling test for breast cancer would be one example of an IVDMIA.

Food and Drug Administration (FDA) clearance or approval is not required for LDTs.  The laboratory that develops and performs the test is regulated by the Center for Medicare and Medicaid Services (CMS) through the Clinical Laboratory Improvement Amendments (CLIA).  The labs obtain a CLIA license and perform all the tests in their own facility.  CLIA regulates the development and analytical performance of LDTs, requiring the tests to meet standards for accuracy, precision, total sensitivity, and total specificity.  Over the past few years, the disccusion about the regulation of analytical and clinical validation of LDTs and the role of the FDA has intensified.  The policy of the FDA, until recently, has been one of “enforcement discretion,” meaning that the FDA believes it has the legal authority to regulate LDTs but has chosen not to.  The FDA recently announced an end to its policy of enforcement discretion for LDTs, and a new regulatory framework for LDTs is being drafted (more on that in the next post).  This proposed change in the oversight of LDTs has become quite controversial, to say the least.

The explosion in the number of patients tested by LDTs, particularly patients with (or at risk for) breast cancer, has prompted several questions....

Some in the regulatory agencies and healthcare have asked: How are patient safety and the effectiveness of the tests for the intended uses established?  Do we want treatment decisions for tens of thousands of patients to be based on tests over which the FDA exercises no oversight?  What type of premarket evaluation by the FDA (if any) should be required?

Members of industry and healthcare providers have asked: How will an increased regulatory burden affect assay development?  How will analytical and clinical validity be balanced with patient safety and access to cutting-edge technology that may help guide treatment decisions?  Will reimbursement for the tests keep up with the anticipated increased costs of development and compliance?

What do you think? Is FDA oversight of LDTs is long overdue or a new and unnecessary barrier to innovation in complex diagnostic testing?

In the next installment, I will briefly discuss recent developments in regulation of LDTs through the end of 2010.  Ben Calhoun

Ben Calhoun is a practicing surgical pathologist in Charlotte, North Carolina with expertise in breast pathology.  He trained at Yale and Vanderbilt and went to medical school and graduate school at the Medical College of Georgia. He is the Medical Director of Surgical Pathology for Carolinas Laboratory Network and, in his spare time, is an MBA student in the McColl School of Business at Queens University in Charlotte (anticipated graduation in December 2011).

Ben's initial posts have focused on Accountable Care Organizations (ACOs) and Laboratory Developed Tests (LDTs).