scope:

This guideline provides protocols for evaluating commutability of processed samples when tested with quantitative measurement procedures. Such processed samples may be those created for proficiency testing/external quality assessment (PT/EQA), measuring interval verification sample sets, or QC samples. Processed samples can also be human specimens that are modified in a way that may change their measurement characteristics. In such cases, only a few processed samples (eg, three to five) should be evaluated to represent the behavior of the modification process being assessed. This restriction is suggested because the underlying analyses in this guideline do not account for the simultaneous assessment of many processed samples. CLSI document EP39¹ mentions the use of surrogate samples for measurement procedure performance testing, sometimes using many such samples, eg, for measurement procedure comparison studies. EP14 does not provide methods to screen a large number of samples in such cases.

This guideline is intended for developers of commercial diagnostic tests as well as laboratory-developed tests. This guideline is also useful for manufacturers of measuring interval sample sets and QC samples, and for PT or EQA providers to determine whether their processed samples are commutable with patient samples when examined with specified measurement procedures. Other options for assessing the commutability of processed samples across multiple measurement procedures are covered in CLSI document EP30² and in the literature.³

This guideline may also be useful to all clinical laboratory professionals wishing to investigate the commutability of a processed sample analyzed with a specific in vitro diagnostic (IVD) device in their laboratory.

EP14 is intended to assist in the education of clinical laboratorians and diagnostic manufacturers about the commutability of processed materials and how a sample's matrix can affect some measurand values and their interpretation (referred to as matrix effects). For example, professionals may not be warned of a matrix effect caused by the interaction of processed PT/EQA material and the measurement procedure, and therefore the data may suggest to them that erroneous patient results are being generated, when in fact the results may be acceptable. Examples of a matrix effect due to the interaction of a processed QC and certain reagent lot(s) exist in the literature.⁴ Therefore, these types of effects should not be a surprise to experienced laboratory staff and should not lead to erroneous conclusions about the suitability of results for patient samples. This guideline should assist all interested parties in not only evaluating the presence or absence of a matrix effect, but also by increasing awareness that the intended use of a processed matrix potentially affects patient care.

This guideline can also be used by laboratorians performing quantitative tests for a wide variety of measurands across various disciplines to understand the commutability of processed samples.

Finally, an added benefit to following the protocol is that manufacturers and PT/EQA providers should be able to provide documentation to government or accrediting agencies on processed samples commutability to help avoid false conclusions about the adequacy of patient testing.

It should be noted that although the protocol in this document is intended to help distinguish between effects caused by measurement procedure malfunctions and those caused by the use of artificial or human-based processed samples, it does not describe approaches that specifically establish the exact mechanism or reason for any observed noncommutability. This guideline does not apply to qualitative tests that supply only "yes/no" or "positive/negative" results.

This guideline is not intended for validating a measurement procedure during the regulatory submission process when the types of processed samples mentioned above are not products of IVD device manufacturers. The most common use of this guideline by IVD device manufacturers is as a troubleshooting tool when independently created processed sample sets do not behave as expected. It may also be used during measurement procedure development to ensure that processes such as freezing, spiking, or diluting do not change the commutability of patient samples. See CLSI document EP34⁵ for more information.

Also, it should be noted that this document is not intended to be used to evaluate specimen type differences, such as serum vs plasma. Such comparisons are covered in CLSI document EP35.⁶