United States of America (USA, US)

Regulatory overview

In 1988, the US government passed the Clinical Laboratory Improvement Amendments act (CLIA 88 or CLIA), which specified regulations and standards for all facilities in the United States that perform laboratory testing on human specimens for health assessment or the diagnosis, prevention, or treatment of disease.¹²¹ CLIA classifies tests by a complexity model rather than testing location or intended use and tests are defined as waived, of moderate complexity or high complexity. Waived tests include test systems cleared by the Food and Drug Administration (FDA) for home use and those tests approved for waiver under the CLIA criteria. The only criteria for non-accredited laboratories to perform waived tests is for the device to have been cleared by the FDA, for operators to follow manufacturer’s instructions as a minimum requirement (including perform quality control (QC) at the frequency defined in the manufacturers package insert), and to allow random inspection of the testing facility to establish compliance.¹²² Of note however, is that all laboratories which perform testing on human samples (with the exception of defined research laboratories and personal home use testing) are required to be certified (registered) by the Centers for Medicare and Medicaid Services (see below) in order to perform any testing procedure. In this regard, “laboratory” essentially means any site where testing occurs, including a hospital ward, a doctors office, community testing facility or ambulatory testing service.

The CLIA requirements are administered through the Centers for Medicare and Medicaid Services (CMMS), which regulate all laboratory testing (except research) performed on humans. CMMS is the agency which provides testing certificates; a laboratory which performs moderate complexity or high complexity tests requires a certificate of compliance and a laboratory which performs only waived tests may apply for a certificate of waiver. In total, CLIA covers approximately 200,000 laboratory entities. The Division of Laboratory Services, within the Survey and Certification Group, under the Center for Medicaid and State Operations has the responsibility for implementing the CLIA program.¹²³

In addition to CMMS which administers the CLIA program, the Secretary of Health and Human Services under whose authority and oversight the CLIA program operates, is required to develop appropriate standards to assure consistent, accurate, and reliable test results by all clinical laboratories. To this end, the Secretary is authorized to establish advisory committee(s) to assist with this process. The Clinical Laboratory Improvement Advisory Committee (CLIAC) was established in 1992 “to provide scientific and technical advice and guidance to the Secretary and the Assistant Secretary for Health regarding the need for, and the nature of, revisions to the standards under which clinical laboratories are regulated; the impact on medical and laboratory practice of proposed revisions to the standards; and the modification of the standards to accommodate technological advances”.¹²⁴

A twenty year review of CLIA regulations with comments from the principal agencies involved with laboratory regulation and accreditation is provided by the CLIAC summary report for the meeting of February 2008, “Recognising 20 years of CLIA”.¹²⁴ In addition, the complete set of CLIAC meeting summaries is available through the Centers for Disease Control and Prevention (CDC).¹²⁵

Accreditation agencies

Accreditation inspections are provided by a number of organizations, and laboratories are free to choose which of these they prefer. Laboratories may choose a state agency (usually a state department of health), or one of the inspection and accreditation agencies approved by CMS. Major accrediting agencies in the US include the College of American Pathologists (CAP), the Joint Commission (JC; previously the Joint Commission on Accreditation of Healthcare Organizations (JCAHO)), and COLA (formally the Commission on Office Laboratory Accreditation, now just referred to as “COLA”). A brief history of JCAHO and COLA is given in the Clinical Laboratory Improvement Advisory Committee (CLIAC), summary report of meeting, “Recognising 20 years of CLIA”, February 2008.¹²⁴

COLA is an independent organization which was founded in 1988 to assist laboratories stay in compliance with (the then new) CLIA regulations¹²⁶ . In 1993, the Health Care Financing Administration (now CMS) granted COLA authority as an accrediting agency. COLA is strongly supported by American medical colleges including the American Medical Association, the American College of Physicians, the American Academy of Family Physicians, the American Osteopathic Association and the College of American Pathologists. COLA currently accredits approximately 7,000 facilities, including many of the physician office and hospital laboratories (with physician office laboratories probably their primary market).

A succinct overview of the categorization of laboratory tests (waived, moderate and high complexity) and the US accreditation procedures and accrediting organizations is provided by Sautter and Lipford.¹²⁷

Current issues with performance quality and fitness for purpose

The original list of waived tests was relatively small and consisted mainly of “dipstick” tests for urine and some monitoring devices cleared by the FDA for home-use (for example blood glucose). However, the list of wavered tests has grown considerably over the years and was revised in 2008 to include a large number of analytes, including many which can be performed at POC.¹²⁸ Tests which remain in the moderate complexity category (and thus require full accreditation) include blood gas instruments and all activated clotting time tests.

With the increased use of waived tests outside of the accredited laboratory environment, there has also been increasing concern as to the quality of results and the potential harm to patients. The identification of quality issues in waived testing sites has been compiled from on-site inspection reports obtained by CMMS during the period 1999 to 2003 and summarized by the CDC in their report and recommendations paper Good Laboratory Practices for Waived Testing Sites, 2005.⁶² In addition to a review of quality failures, the CDC document provides recommendations developed by CLIAC for improving the quality of waived tests. More recently, the on-going issues with regard to the quality of waived tests was discussed at length during the CLIAC meeting of February 2008.¹²⁴

In addition to the quality issues identified through CMMS inspections, there is currently an ongoing debate within the scientific community and within FDA with regard to the quality of blood glucose and haemoglobin A1c (HbA1c) testing devices. As indicated previously, queries have been raised as to their correct and intended use and their fitness for purpose. Many laboratories performing only waived tests however, do actually seek laboratory accreditation, follow one of the many professionally based POCT operational guideline documents, perform quality control, and participate in external quality assurance. Laboratories which perform moderate and high complexity tests which require full accreditation, often have all testing procedures (including any waived tests which they may perform) included within the accreditation. This will also depend on the internal “policy” of the chosen accrediting agency; for example, the College of American Pathologists (CAP) require all tests to be accredited,⁶⁴ while some state accrediting agencies only mandate the minimum CLIA requirement.

Professional support for accreditation

Good support for accreditation of laboratories performing only waived tests is provided by the main medical college responsible for “general practitioners” or “family medicine physicians”. The American Academy of Family Physicians actively supports accreditation of the physician office laboratory (POL),¹²⁹ both through its family medicine residents training program and its support for the COLA laboratory accreditation scheme.⁶³,¹²⁹

To further assist laboratories with the accreditation process and to provide guidance in establishing and maintaining quality testing procedures, there are many “standards” and “guidelines” available. The Clinical Laboratory Standards Institute (CLSI) is the principal provider of “standards” to the pathology and associated diagnostic industry in the US, even though ISO 15189 is used by the major diagnostic laboratories and forms the basis for many of the CLSI, CAP and JC standards. A list of CLSI standards and guidelines relevant to POCT is provided as appendix 5.