CLIA Testing Procedures & Method Validation 3 — Questions and Answers
Question 1: In method validation, 'analytical specificity' refers to a method's ability to:
- Detect very low concentrations of analyte
- Measure only the intended analyte without interference from other substances (Correct answer)
- Produce consistent results across runs
- Perform accurately across a wide dynamic range
Correct answer: Measure only the intended analyte without interference from other substances
Analytical specificity is the ability of a method to measure solely the target analyte even in the presence of potentially interfering substances.
Question 2: Which CLSI guideline specifically addresses evaluation of precision of quantitative measurement procedures?
- EP05 (Correct answer)
- EP07
- EP09
- EP15
Correct answer: EP05
CLSI EP05 is the guideline for evaluation of precision (repeatability and within-laboratory imprecision) of quantitative measurement procedures.
Question 3: A laboratory notices that results from a new cholesterol analyzer are consistently 5 mg/dL higher than the reference method across all concentrations. This finding most likely indicates:
- Random error
- Proportional systematic error
- Constant systematic error (Correct answer)
- Increased imprecision
Correct answer: Constant systematic error
A fixed offset that remains constant regardless of analyte concentration is classified as constant (systematic) bias.
Question 4: What does the term 'limit of quantitation' (LoQ) describe in laboratory testing?
- The lowest concentration that can be distinguished from zero with 95% confidence
- The lowest concentration that can be measured with acceptable precision and accuracy (Correct answer)
- The highest concentration the assay can reliably measure
- The concentration at which two methods agree within 10%
Correct answer: The lowest concentration that can be measured with acceptable precision and accuracy
The LoQ is the lowest analyte concentration that can be quantitatively measured with acceptable precision (typically CV ≤20%) and accuracy.
Question 5: During a method validation for a moderately complex test, a laboratory calculates a total allowable error (TEa) of 10%. The observed total error is 12%. What action is required?
- Accept the method because the error is close to the limit
- Reject the method and investigate sources of error before patient use (Correct answer)
- Report results with a disclaimer flag
- Increase the number of QC samples
Correct answer: Reject the method and investigate sources of error before patient use
When observed total error exceeds TEa, the method fails validation and must not be used for patient testing until the source of error is identified and corrected.
Question 6: Which type of QC procedure evaluates performance between different analysts, instruments, or time periods within the same laboratory?
- Within-run precision
- Between-run (intermediate) precision (Correct answer)
- Reproducibility
- Analytical sensitivity
Correct answer: Between-run (intermediate) precision
Between-run (intermediate) precision captures variability across different runs, days, analysts, or instruments within one laboratory.
Question 7: Under CLIA regulations, the laboratory director must approve which document before a new test is placed into service?
- The billing code assignment form
- The standard operating procedure (SOP) (Correct answer)
- The reagent purchase order
- The proficiency testing enrollment form
Correct answer: The standard operating procedure (SOP)
CLIA requires the laboratory director to review and approve the standard operating procedure (SOP) before a test is used for patient care.
CLIA Testing Procedures & Method Validation 3
In method validation, 'analytical specificity' refers to a method's ability to: