International Standards Organization (ISO) provides an answer.
There are proficiency testing schemes commercially available for hundreds of analytes from the ten Centers for Medicare and Medicaid Services (CMS)-approved proficiency testing (PT) provider vendors—yet there are thousands of different types of laboratory analyses occurring daily. The purpose of this article is to share approaches for assuring quality in testing when CMS-approved proficiency testing schemes are not available.
42 CFR Part 493.1236 2(c) requires that “At least twice annually, the laboratory must verify the accuracy of the following: (1) Any test or procedure it performs that is not included in subpart I of this part. (2) Any test or procedure listed in subpart I of this part for which compatible proficiency testing samples are not offered by a CMS-approved proficiency testing program.” Accreditation bodies have applied differing approaches for meeting requirements for these analytes, which has created some confusion in the laboratory community. For the purposes of this article, proficiency testing programs are considered synonymous with external quality assessments.
ISO 15189:2012 Medical laboratories—Requirements for Quality and Competence is an international standard written specifically for laboratories conducting testing on samples derived from the human body and is widely used by more than 6,000 laboratories around the world. The standard is composed of both quality management system requirements and technical requirements. Although participation in proficiency testing is a requirement of ISO 15189:2012, the standard includes alternative approaches to assuring quality when proficiency testing or external quality assessments are not available.
Use of certified reference materials
Laboratories can procure materials that have a reported known value and are accompanied with a certificate or product information sheet. Certified reference materials (CRMs), ideally, would be obtained from competent reference material producers (demonstrated by ISO 17034 accreditation) or National Metrology Institutes such as the National Institute of Standards and Technology (NIST) in the United States. The CRMs have property values that are traceable to a stated reference; however, these are sometimes not available for the desired material. Even if they are available, they can be very expensive. Other types of reference materials (RMs) can be useful, such as materials with informational (not certified) property values (e.g., “assayed” control materials, or materials with known identity, such as positive or negative). A common practice is for the laboratory to establish a protocol whereby it tests the RMs at planned intervals, establishes acceptance limits, and produces charts to detect trends. There is a wide variety of ways to demonstrate acceptance or trends; the ISO requirements are intended to be general in order to encourage innovative approaches.
Use of samples previously examined
Previously examined samples can provide a cost-effective and reliable means of assuring accuracy in testing. Common approaches include blinding previously-examined samples and retesting them; providing them to different analysts for comparison; or providing blinded samples to be run on different types of calibrated and traceable instrumentation.
Material from cell or tissue repositories
Biobanks, tissue banks, and biorepositories are sources from which laboratories may obtain samples. In advance of contracting with the biobanks and repositories, it is suggested that laboratories conduct an appropriate level of research to ensure that the products and services they offer meet the needs of the laboratory and that they have credentials in place to demonstrate a review from an independent third party. Materials from repositories could have a variety of certified and informational properties, both quantitative and qualitative. Depending on availability and cost, they could be used to verify new measurement or test methods, as occasional QC samples, or as calibrators.
Inter-laboratory comparison programs
This approach includes inter-laboratory comparison of results on similar samples. This can include split-sample comparisons (also called bilateral comparisons) with one or more other competent laboratories. This has been successful for novel biological markers or for experimental methods. Other types of inter-laboratory comparisons could include studies to characterize a reference material, or a study to validate a measurement method. If a laboratory’s results are included in the final claims for the method, or for a characterized property of a reference material, that is evidence of competence in the study.
Another option is for laboratories to look outside of the CLIA-approved group of providers, and investigate offerings from other competent proficiency testing providers when CLIA-approved PT providers do not offer the specific PT scheme relevant for the testing performed by the laboratory. There are several recognized proficiency testing schemes for esoteric analytes; some of these offered by government agencies (e.g., CDC, FDA, DoD, DOE, DoA), universities, and public health organizations. A growing number of these programs are accredited to ISO/IEC 17043 for international recognition and for quality improvement.
In North America, there are two broad-scope proficiency testing providers for the general laboratory medical community, and at least three proficiency testing providers in subspecialties of IVD measurements in human and animal disease and vaccine research, radiochemistry, and select biological and biochemical agents. Current examples of clinical proficiency testing providers accredited to ISO/IEC 17043:2010 include Clinical Microbiology Proficiency Testing (CMPT), Duke University Medical Center—Duke Human Vaccine Institute, and Institute for Quality Management in Healthcare (IQMH). These providers add breadth of proficiency testing schemes to the existing CMS-approved providers. Successful participation in appropriate programs should satisfy accreditation and CLIA requirements.
ISO/IEC 17043:2010 includes requirements for a quality management system as well as technical requirements for personnel, equipment, facilities, scheme design, homogeneity and stability testing, and data analysis and evaluation of proficiency testing scheme results. Accreditation to ISO/IEC 17043:2010 by third-party Accrediting Bodies demonstrates the PT provider’s competence for the planning and implementation of proficiency testing programs. Accreditation also provides users of proficiency testing programs (including clinical laboratories) increased confidence that the programs relied upon are operated in accordance with specified technical and management system requirements.
When seeking proficiency testing schemes in which to enroll (CMS-approved or ISO/IEC 17043-accredited), it is important to ensure specificity in the request. The goal is to obtain a challenge that is as close as possible to real-life patient samples that the laboratory is testing. There is little value in participating in a proficiency testing scheme that is of a different matrix or is of a concentration that may not be within the normal operating parameters of the laboratory’s instrumentation. Providers in the industry have been supportive to laboratory clientele in providing guidance on the relevance of proficiency testing schemes to the laboratory’s work. Internationally-recognized accreditation bodies post “live” website directories that include a listing of the currently ISO/IEC 17043-accredited proficiency testing providers and the associated Scopes of Accreditation which identify the schemes accredited.
Daniel W. Tholen, BS, MS, was the convenor for the working groups responsible for the drafting of ISO/IEC 17043:2010 and ISO 13528, respectively. Dan Tholen Statistical Consulting, Traverse City, MI, provides statistical consulting and serves as an American Association for Laboratory Accreditation (A2LA) assessor.
Randall Querry, BA, has been employed by A2LA since 1998, and is currently the Accreditation Manager for Clinical, Forensics and PT Provider Accreditation Programs. He conducts assessments, oversees assessors, and serves as a lead peer evaluator on international accreditation body evaluations in support of the regional mutual recognition arrangements.