Interferences with clinical laboratory tests can create discrepancies in test results which can lead to patient harm. In clinical chemistry, interference is defined as a cause of medically significant difference in the measurand test result due to another component or property of the sample. Although performance is monitored by internal QC and external quality assessment procedures, laboratories can’t easily detect error caused by interferents.
The three main contributors to testing inaccuracy are imprecision, method-specific difference, and specimen-specific difference (interference).1,2 Frequently, measurement procedure evaluations estimate only the first two. Specimen-specific difference, or interference, is often viewed as an isolated occurrence rather than as a quantifiable characteristic of the measurement procedure.
Interferents may originate from endogenous and exogenous sources:
Interference is identified by screening for an interference effect followed by quantifying interference effects. This is accomplished by using a paired-difference study, when warranted. In a paired-difference study, the prepared sample contains the potential interferent, and the prepared control sample does not. All other potentially contributing factors remain the same in the test and control samples. Interference is calculated as the difference between the prepared test and control samples.
Interference with laboratory tests can occur before testing during the preexamination (pre-analytical) phase or during the examination (analytical) phase.
A change in the measurand or its concentration before analysis is commonly termed a “preexamination effect.” Although such effects may influence the medical use of a laboratory result, they are not analytical interference.
Common examples of preexamination effects are:
Some causes of examination (analytical) interference are as follows:
CLSI’s Interference Testing in Clinical Chemistry—EP07, provides background information, guidance, and experimental procedures for investigating, identifying, and characterizing the effects of interferents on clinical chemistry test results. EP07 assists manufacturers and laboratories with evaluating interferents, determining the extent of interfering effects in the context of medical needs, and informing customers of known sources of medically significant error. EP07 identifies many potential interferents to be evaluated in the risk management process.3 Laboratory scientists and manufacturers need to understand the scientific concepts, make informed choices, and work together toward the common goal of safeguarding patient care. Identifying an interference effect, evaluating its medical significance, determining its underlying cause, and ultimately improving the measurement procedure necessitates close cooperation between the laboratory and the manufacturer.
CLSI also offers a solution package of seven documents that focuses on topics such as interference, linearity, reference intervals, trueness, and precision, including related troubleshooting. Topics covered in this package correspond to CLSI quality system essential Process Management and ISO 15189 sections 5.4 Pre-examination processes and 5.6 Ensuring quality of examination results.