Interference

Interference occurs when a chemical substance present in a patient specimen causes a measurement result to deviate from the true analyte concentration. Common interferents include endogenous substances — such as bilirubin, hemoglobin, lipids, and paraproteins — as well as exogenous compounds such as drugs and contrast agents. Unlike imprecision or calibration error, interference is often invisible to routine QC because it is specimen-specific and may not affect control materials.

The Interference module supports two complementary study designs per CLSI EP07: Paired Difference (screening) and Dose Response (characterization). Paired Difference testing determines whether a specific interferent at its maximum expected concentration causes a statistically and clinically significant bias. Dose Response testing quantifies the interference relationship across multiple interferent concentrations, identifies the maximum concentration at which interference remains within acceptable limits, and fits a regression model to characterize the dose-dependent effect. Both experiments can be run independently or combined in a single study.

Scope: This module evaluates interference from chemical substances (endogenous and exogenous). It does not cover physiological conditions (eg, pregnancy, diurnal effects) or environmental effects (eg, heat, sunlight), which are outside the scope of CLSI EP07.

When to Use This Module

Interference testing is required or strongly recommended in the following situations:

New method or instrument implementation — Before a measurement procedure enters routine use, interference from common endogenous substances (bilirubin, hemolysis, lipemia) and relevant exogenous compounds should be verified to confirm the manufacturer's interference claims are reproducible in the laboratory.
Discrepant patient results — When a patient result is inconsistent with clinical presentation or a previous result from the same patient, an unsuspected interferent should be investigated as a potential cause. The module supports targeted characterization of specific suspected substances.
Analytes with known high-risk interferents — Certain analytes are particularly susceptible to known interferents. Laboratories should verify that interference remains within allowable limits for their specific patient population and typical specimen characteristics.
Reagent or method modification — Changes to antibody, reagent matrix, or calibration may alter the measurement procedure's selectivity and require re-evaluation of interference susceptibility.
Accreditation requirements — CAP and CLIA require documentation of interference testing as part of method verification for non-waived quantitative tests.