Clinical Chemistry I Week 03&04 Quiz

Clinical Chemistry I - 0202304

• Course instructor: Mohammad QABAJAH
• Email address: [email protected]
• Course covers week 03&04, Method Selection and Evaluation

Objectives

• Familiarize with three key areas for analytical method selection.
• Understand analytical performance of methods.
• Be aware of analytical and practical performance criteria, focusing on automated methods.
• Recall statistical concepts related to analytical performance of methods.
• Compare analytical performance criteria using raw data through Bland-Altman method and correlation regression.

Method Selection: Considerations

• Medical Usefulness: Optimal patient care and clinical needs of the lab test.
• Analytical Performance: Calibration, precision, accuracy (trueness), analytical range, detection limit, clinical sensitivity and specificity are essential.
• Practical Criteria: Detailed protocol, reference materials, reagent stability, technologist skill, potential hazards/waste, specimen requirements, instrument specifics, cost, computer platforms, technical support, automated procedure specifics (pipetting precision, carryover, detector imprecision, reagent stability, time-to-report, overall throughput, mean time to repair.)

Statistical Terms

• Mean: Sum of values divided by the total number of values.
• Standard deviation: Measures the amount of variation or dispersion of a set of values.
• Coefficient of variation: The ratio of the standard deviation to the mean, expressed as a percentage.

Gaussian Probability Distribution

• Measures the probability of a data point falling within a certain range around the mean.
• Common values displayed include 68%, 95%, and 99.7% ranges.

Analytical Methods: Basic Terms

• Calibration: Correlation between instrument signal and analyte concentration.
• Linearity: Relationship between measured and expected values over the analytical range.
• Trueness/Accuracy: Closeness of agreement of the average measured value with the true value.
• Precision: Closeness of agreement among independent measurements.
• Limit of Detection (LoD): The smallest concentration of an analyte that can be reliably detected above background noise.
• Limit of Blank (LoB): The smallest concentration that can be detected without the presence of the analyte.

Calibrator

• Known quantity used for calibration.
• Calibration curves can be linear or curved (e.g., four-parameter logistic functions in immunoassays).
• Curves should be monotonic.
• Calibration signal stability and frequency are important.

Trueness and Accuracy - Related Terms

• Recovery: Measured concentration difference from the added amount.
• Drift: Instrument or reagent instability over time.
• Carryover: Influence of previously measured samples on subsequent measurements.
• Bias: Difference between the average measured value and the true value.

Precision - Related Terms

• Repeatability: Closeness of results for measurements made under identical conditions.
• Reproducibility: Closeness of results from measurements made under different conditions.
• Imprecision: Measured by standard deviation and coefficient of variation, and attributable to random error. Types include between-run precision and interlaboratory precision.

Analytical Measurement Range and Limits of Quantification

• Reportable range over which measurements are within the established imprecision and bias tolerances for that method.

Analytical Range

• The range of concentrations where measurements are reliable and within tolerated levels of imprecision and bias.

Limit of Detection (LoD) & Limit of Blank (LoB)

• Important for analytes such as hormones; factors like instrument sensitivity, sample matrix, background noise, and analyte properties impact these limits.

Analytical Sensitivity

• Indicates the ability of the method to detect small changes in analyte concentration.
• Slope of the calibration curve is directly related
• Random variability (precision) (inverse relationship)

Analytical Specificity and Interference

• The ability of a procedure to accurately measure a specific analyte, even if other substances are present.

Analytical Goals

• Based on clinical outcomes or setting, biological variability, imprecision (bias <0.25× (σ2within-B + σ2 between-B)0.5 ), standards from regulatory bodies.

Method Comparison

• Comparison study considerations include sample number, analyte concentration distribution, sample representativeness, practical aspects (storage, sample treatment, anticoagulants, time for measurements), and ethical issues.
• Bland-Altman plot and regression analysis are used to evaluate the differences between methods.

Comparison of Methods—Proportional random error

• Depends on the change in a variable, directly related.

Comparison of Methods—Traceability

• Unbroken chain of comparisons to known reference standards. Includes calibration chain connecting to primary national/international standards.

Comparison of Methods—Uncertainty

• Parameter characterizing the dispersion of measurement values.
• Values expressed with standard deviation and probability (e.g., 95%).
• Affected by preanalytical variation, method imprecision, sample-related interferences, uncertainties related to calibration, and bias corrections.

This quiz tests your understanding of analytical method selection and evaluation in clinical chemistry. Focus areas include medical usefulness, analytical performance, and practical criteria essential for optimizing lab tests. Have a firm grasp of statistical methods and performance evaluation techniques for assessment.