Clinical Testing has Changed – Should CLIA?

Much of my professional life in the mid-1990s was spent uttering the mantra, “A test is a test is a test.”

It meant that the Clinical Laboratory Improvement Amendments of 1988 (CLIA) should not be site-specific – a test is a test no matter where it is performed. Back then, there was a constant cry for physicians’ offices to be exempt from the law – arguing that their in-office laboratories would cease to exist under the regulation. Physician office laboratories lost their exemption battle; however, they may have won the war.

Today, these labs make up the bulk of testing sites. In fact, according to the Centers for Medicare and Medicaid Services (CMS) March 2020 CLIA database, over 45 percent of all CLIA laboratories are described as physician office laboratories (1). In comparison, only 3.42 percent of laboratories are in hospitals.

Just over 30 years have passed since the first regulations implementing CLIA were finalized. Since then, CLIA has improved clinical laboratory performance – from analytical oversight to personnel credentials and quality markers. A federal advisory panel, the Clinical Laboratory Improvement Advisory Committee (CLIAC), was established to “provide scientific and technical advice and guidance to the Secretary”of Health and Human Services (2). To this day, the panel of experts, along with staff from the Centers for Disease Control and Prevention (CDC), CMS, and the Food and Drug Administration (FDA), deliberate on laboratory practice and standards and propose modifications to the regulations alongside scientific and technological advancements.

By many measures, CLIA has worked successfully. Laboratories are now held to standards – for instance, limiting the number of Pap smear slides a laboratory technologist may screen in a day or mandating that all cytology slide preparations be evaluated on the laboratory premises. An external, objective measure of laboratory accuracy, known as proficiency testing, must be treated in the same manner as patient specimens for proper assessment. The basic act of obtaining registration, certification, or accreditation is now required for accountability – and so it is no surprise that damning newspaper headlines such as “Medical Labs, Trusted as Largely Error-Free, Are Far from Infallible”(3) are long gone.

The CLIA triumvirate of the CDC, CMS, and FDA collaborate well and make regulatory adjustments as the law allows – but is it enough?  Does CLIA have the capability to respond not only to the different types of laboratory facilities, but also to the life cycle of a clinical laboratory test and its advancements? The answer is a resounding “maybe.”

Clinical testing has changed; there is no doubt about it. CLIA places laboratories into categories based on the type of testing performed – waived, provider-performed microscopy, moderate-complexity, or high-complexity. A laboratory may qualify for a certificate of waiver if the testing performed “employ(s) methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible” or “pose no reasonable risk of harm to the patient if the test is performed incorrectly” (42 CFR 493.15). Like the volume of physician office laboratories, the number of waived laboratories has exploded.

Monique Spruill, Director of the CMS Division of Clinical Laboratory Improvement and Quality, reported at the CLIAC 2021 meeting, 220,862 CLIA laboratories hold a certificate of waiver and 29,883 are designated as provider-performed microscopy (1). Together, these laboratories make up a whopping 85 percent of all 296,815 CLIA laboratories. In the midst of the COVID-19 pandemic, the number of laboratories enrolled in CLIA grew by 37,989 (March 2020 to March 2021). Of those, 92 percent were designated as waived.

To maintain certificate eligibility, waived laboratories must follow manufacturers’ instructions for performing the test. They are subject to inspection if: there is a substantive reason to believe the lab is operating in a manner that creates “imminent and serious risk” to human health; there are complaints from the public; or to determine if the laboratory is conducting only waived tests. With the sheer volume of these labs and waiver from oversight, it is no surprise that they are not regularly reviewed. Waived laboratory testing is important – but can be fallible. Think about how a laboratory test, even a simple one, impacts medication dosing, coagulation monitoring for blood clots, or diagnoses of HIV or hepatitis C.

A report published in 2005 on Good Laboratory Practices for Waived Testing Sites shared CMS survey findings from waived testing sites (4). While most surveyed sites followed accurate and reliable testing practices, “lapses in quality were identified at certain sites, some of which could result in patient harm.” Quality deficiencies included: not possessing current manufacturer instructions; not checking product inserts for changes; not performing quality control or required confirmatory tests; and not documenting the name and expiration date for all tests performed, among others. The report also provided an educational guide to improving the quality of waived testing laboratories.

With the growing number of waived laboratories and point-of-care technologies, ensuring accuracy in this area is paramount. As foretold by Jeffrey Shuren and Timothy Stenzel, national investment in point-of-care technologies and assessments will allow for rapid expansion of testing capacity and patient access (5).

An updated CLIA may provide an opportunity to assess the effectiveness of existing educational efforts, oblige accountability for improvement, and expand on data collection and analysis.  It may also create a mechanism for ensuring the reliability of tests delivered at point-of-care and in settings not currently covered by CLIA.

Proficiency testing evaluates laboratory accuracy and provides an objective tool for assessing the competency of personnel and the proper operation of equipment, specimen handling, and reporting functions. CMS maintains a list of analytes for which proficiency testing is required (6); however, it was last updated in 2003. An updated CLIA may establish a mechanism for adding and deleting regulated analytes in a more timely manner. Furthermore, if non-laboratory healthcare professionals assume clinical testing roles in the future, CLIA might consider offering proficiency testing for individuals performing moderate- and high-complexity testing, rather than for the whole laboratory.

Qualitative demands for the clinical laboratory have increased in complexity – making the case for standardized methods for new technologies. Proficiency testing is an important component of these standards and should be treated with more agility under CLIA. Quality assessment tools must also keep pace with the acceleration of genomic technologies.

CMS last published its list of top 10 CLIA deficiencies in October 2018 (7), including the percentage of labs with poor storage of reagents (4.8 percent), lack of proficiency testing (4.3 percent), and no quality assessment program (4.0 percent), among other concerns. The two preceding decades counted similar CLIA deficiencies – from proper storage of reagents and specimens to lack of analytic systems/quality assurance; from failure to follow manufacturer instructions to personnel concerns. Although the types of deficiencies remain somewhat similar in recent years, the percentages fluctuate. It’s a game of whack-a-mole in which some laboratories make improvements and others do not.

CMS gives private nonprofit accreditation organizations the authority to accredit clinical laboratories under CLIA. Accredited laboratories must meet specific CLIA standards and comply with the accreditation program’s requirements. Under CLIA, an accredited laboratory with a deficiency might provide a corrective action plan; however, this does not necessarily mean systemic change is occurring. An updated CLIA might seek incentives for laboratories to achieve ISO 15189 accreditation (an international standard) to implement an effective management system. ISO 15189 integrates review of pre- and post-analytical testing activities – where most errors occur – and includes system-wide processes for mitigating laboratory errors and improving performance. CLIA already recognizes ISO 15189 accreditation for clinical laboratories, but it is not widely used in the US.

The old “a test is a test is a test” mantra is no longer necessary for this regulation; there are tools, such as CLIAC, available to improve and update CLIA. The federal advisory panel has been a sustaining voice in requiring the three agencies – and a variety of laboratory experts – to discuss ongoing issues and recommend solutions. Now, the time is right for it to consider the next generation of CLIA.