CLIA Testing Procedures & Method Validation 5 — Questions and Answers
Question 1: Which of the following best defines the 'analytical measurement range' (AMR) of a quantitative laboratory test?
- The range of values that appear on a patient's lab report
- The span of analyte concentrations over which the method produces accurate, linear results without dilution or concentration (Correct answer)
- The range of control concentrations used for daily QC
- The interquartile range of reference population values
Correct answer: The span of analyte concentrations over which the method produces accurate, linear results without dilution or concentration
The AMR is the range of concentrations over which a method can directly report accurate results without sample manipulation such as dilution.
Question 2: A new immunoassay for thyroid-stimulating hormone (TSH) shows excellent precision but consistently underestimates TSH in patients with high heterophile antibody titers. This is an example of:
- Random error
- Proportional bias
- Endogenous interference (Correct answer)
- Calibration drift
Correct answer: Endogenous interference
Heterophile antibodies are endogenous interferents that can disrupt immunoassay signal, leading to falsely low or high results despite good precision.
Question 3: Under CLIA, which of the following personnel may NOT serve as the technical consultant for a moderate-complexity laboratory?
- A physician with laboratory training
- An individual with a doctoral degree in a chemical or biological science and 1 year of laboratory training
- A medical laboratory scientist (MLS) with 4 years of moderate-complexity testing experience
- A high school graduate with 5 years of bench experience (Correct answer)
Correct answer: A high school graduate with 5 years of bench experience
CLIA requires a technical consultant for moderate-complexity labs to have at minimum an associate degree in laboratory science or equivalent, not just bench experience.
Question 4: When a manufacturer's package insert claims a clinical sensitivity of 95% for a disease marker, this means:
- 95% of healthy individuals test negative
- 95% of individuals with the disease test positive (Correct answer)
- The assay CV is less than 5%
- The method can measure down to the 5th percentile of the population
Correct answer: 95% of individuals with the disease test positive
Clinical sensitivity is the proportion of truly diseased individuals who test positive (true positive rate), not to be confused with analytical sensitivity.
Question 5: During sigma metric analysis for a glucose method, a laboratory calculates: TEa = 10%, bias = 2%, CV = 2%. What is the sigma value?
- 2
- 3
- 4 (Correct answer)
- 5
Correct answer: 4
Sigma = (TEa − |bias|) / CV = (10 − 2) / 2 = 4; a sigma of 4 indicates good method performance.
Question 6: Which document provides the minimum frequency and type of QC materials that must be run for a non-waived quantitative test under CLIA?
- The laboratory's own QC policy
- CLIA 42 CFR Part 493 and CMS guidelines (Correct answer)
- The reagent manufacturer's package insert only
- CAP checklist requirements only
Correct answer: CLIA 42 CFR Part 493 and CMS guidelines
CLIA regulations at 42 CFR Part 493 establish the minimum QC requirements, though accreditation bodies like CAP may impose additional standards.
Question 7: A laboratory is evaluating a new urine dipstick analyzer (waived test). Under CLIA, which performance verification step is required before reporting patient results?
- Full method validation including bias, precision, and linearity studies
- Comparison with at least 40 split patient samples using the reference method
- Following the manufacturer's instructions and verifying the test system works as expected (Correct answer)
- Establishing a site-specific reference interval with 120 healthy subjects
Correct answer: Following the manufacturer's instructions and verifying the test system works as expected
For waived tests, CLIA only requires that laboratories follow manufacturer instructions and confirm the system is functioning correctly — full validation is not required.
CLIA Testing Procedures & Method Validation 5
Which of the following best defines the 'analytical measurement range' (AMR) of a quantitative laboratory test?