CLIA Testing Procedures & Method Validation 2 — Questions and Answers
Question 1: Which statistical measure is used to assess the systematic error (bias) of a new method compared to a reference method during method validation?
- Standard deviation
- Coefficient of variation
- Inaccuracy (Correct answer)
- Imprecision
Correct answer: Inaccuracy
Inaccuracy measures systematic error (bias) — the difference between the new method's mean result and the true or reference value.
Question 2: Under CLIA, when must a laboratory re-validate a test method?
- Every 12 months regardless of changes
- When there is a significant change in reagents, equipment, or methodology (Correct answer)
- Only when a new director is hired
- After every proficiency testing event
Correct answer: When there is a significant change in reagents, equipment, or methodology
CLIA requires re-verification or re-validation whenever a significant change occurs in reagent lots, equipment, or the testing process itself.
Question 3: The Westgard 1₃s rule is violated when:
- One control value exceeds ±2 SD
- One control value exceeds ±3 SD (Correct answer)
- Two consecutive controls exceed ±2 SD
- The range between two controls exceeds 4 SD
Correct answer: One control value exceeds ±3 SD
The 1₃s rule is a warning/rejection rule triggered when a single control result falls outside ±3 standard deviations of the mean.
Question 4: What is the primary purpose of performing a linearity study during method validation?
- To determine the limit of detection
- To confirm the method produces accurate results across its reportable range (Correct answer)
- To measure between-run imprecision
- To assess interference from hemolysis
Correct answer: To confirm the method produces accurate results across its reportable range
A linearity study verifies that the method produces results proportional to analyte concentration across the claimed analytical measurement range.
Question 5: A laboratory introduces a new whole blood glucose analyzer. According to CLIA, what is the minimum number of patient samples required for a comparison-of-methods experiment?
- 10
- 20
- 40 (Correct answer)
- 100
Correct answer: 40
CLIA guidance (and CLSI EP09) recommends a minimum of 40 patient samples spanning the analytical range for a method comparison study.
Question 6: Which interferent category encompasses endogenous substances such as bilirubin, hemoglobin, and lipids that may affect test results?
- Cross-reactants
- Matrix effects
- Endogenous interferents (Correct answer)
- Carryover substances
Correct answer: Endogenous interferents
Endogenous interferents are substances naturally present in the specimen that can falsely elevate or suppress analyte measurements.
Question 7: When verifying the reference interval for a non-waived quantitative test, CLIA guidelines suggest using a minimum of how many healthy reference subjects?
- 10
- 20 (Correct answer)
- 40
- 120
Correct answer: 20
CLIA and CLSI recommend verifying a manufacturer's reference interval with at least 20 healthy reference individuals.
CLIA Testing Procedures & Method Validation 2
Which statistical measure is used to assess the systematic error (bias) of a new method compared to a reference method during method validation?