Each year, nearly 10 billion laboratory tests are performed in the United States. However, before reaching patients, all laboratory tests must be reviewed by the U.S. Food and Drug Administration ("FDA") and assigned a complexity level (low ("waived"), moderate or high). The complexity level dictates where the test can be performed. Moderate and high complexity tests may only be performed in sophisticated laboratories that satisfy the strict requirements of the Clinical Laboratory Improvement Amendments of 1988 ("CLIA") (including personnel training, quality system, proficiency testing and recordkeeping requirements, among others). These labs are known as "non-waived testing labs." On the other hand, if a lab will only perform low complexity tests, most of the CLIA requirements are waived. These labs, which account for nearly 70% of clinical labs in the U.S., are known as "Certificate of Waiver" ("CoW") labs. Unlike many non-waived testing labs, CoW labs have the advantage of providing point-of-care testing.
Point-of-care testing ("POCT"), which may take place at a health-care provider's office or at a facility close by, allows providers to receive lab results for patients quickly and efficiently, oftentimes while the patient is still in the office. POCT eliminates the need to send patient samples to off-site labs for testing, thus reducing wait times for results from days or weeks to hours or minutes. This fast turnaround that comes with POCT can help improve patient outcomes, and save healthcare dollars by providing for faster diagnoses and treatment decisions as well as testing in a facility with lower overhead costs than a non-waived lab. Thus, access to POCT is extremely valuable for both individual patients and the overall public health.
The problem is that FDA's current regulatory process for determining whether a test can obtain CLIA-waived status is inappropriately limiting the availability of POCT. Under CLIA, waived tests are defined to include "procedures that have an insignificant risk of an erroneous result including those that...employ methodologies that are so simple and accurate as to render the likelihood of erroneous results by the user negligible." The "by the user language" is very important. In 1997, Congress added these words to the law to clarify that the CLIA waiver standard needs to focus on the effect that user has on results. If a user needs special laboratory expertise and training to run a test, its use needs to be restricted to non-waived labs. If, on the other hand, "the test performs the same in the hands of untrained users [as] it does in the hands of laboratory professionals under realistic conditions" then it is fine to use the test in a CLIA-waived lab where users will not have the expertise and training of non-waived lab professionals.
The quoted language actually comes from a 2001 FDA guidance document. However, FDA changed its interpretation of the law in 2005 in a new draft guidance. Under the new interpretation, for a test to obtain a waiver, the test must be shown to be comparable to another, different test (preferably a "gold standard" test). FDA also introduced the concept of "allowable total error" into its analysis of test accuracy, taking the focus off of the effect that users on test results and revisiting other unrelated (and irrelevant) sources of error that would already have been considered when FDA first cleared or approved the test. In some cases this leads to a very strange result -- in order to receive a waiver, an applicant must show that their test performs better in CLIA-waived labs than it does in a non-waived lab. This new interpretation was finalized in 2008 FDA guidance, and keeps many good tests out of waived labs.
Reforming the CLIA waiver process is as simple as FDA readopting its former, correct, interpretation of law as set for in its 2001 guidance document. FDA got it right with this interpretation, which focused on the user of test, rather than the test itself, in evaluating test accuracy. Starting from that premise, study designs and statistical methods can be employed to ensure thorough and efficient assessments of waivers to answer the right questions.
Returning to this user-focused approach will allow more safe and effective tests to obtain CLIA-waived status, expanding patient access to POCT improving the public health and potentially reducing health costs.
Improving Access to Point of Care Testing through Sound Science & Regulatory Reform
Coalition for CLIA Waiver Reform