Quality Assurance

Quality management

The coordinated set of activities that ensures laboratory processes consistently produce accurate, reliable, and timey results that are appropriate for patient care and public health decision-making

ISO 15189, DOH-LTO, CAP, NEQAS

Regulatory compliance and accreditation

Accuracy

Denotes closeness to the true value (low bias)

Precision

Denotes the closeness of repeated results (low imprecision)

Systematic error

High precision with poor accuracy

Consistent, predictable deviations from the true value that occur in the same direction each time a measurement is made

Calibration errors, reagent instability, or instrument malfunction

Corrected through QC and calibration verification

Random error

Poor precision (reproducibility)

Unpredictable fluctuations in measurements caused by chance variations in technique, environment, or instrument performance

Cannot be completely eliminated but can be minimized through proper technique and maintenance

Standard deviation and F-test

Parameters and test for precision

Mean and t-test

Parameters and test for accuracy

Sensitivity / true-positive rate

Measures the ability of a test to correctly identify individuals who truly have the disease

Specificity / true-negative rate

Measures the ability of a test to correctly identify individuals who do not have the disease

Positive predictive value (PPV)

Represents the probability that a person with a positive test result truly has the disease

Negative predictive value (NPV)

Represents the probability that a person with a negative test result truly does not have the disease

Do not change with prevalence

Relationship of sensitivity and specificity with disease prevalence

Change with prevalence

Relationship of PPV and NPV with prevalence

High prevalence

High PPV, low NPV

Low prevalence

Low PPV, high NPV

Calibration

Process of establishing the relationship between the measurement response of an instrument and the known concentration or activity of an analyte in a reference material

Calibrators

Specimens with assigned, traceable values, often derived from reference standards

Calibration curve

Ensures that test results are accurate and comparable over time

Controls

Biological or synthetic specimens with known or established target values used to monitor the precision and accuracy of analytical measurements

Not used to establish the calibration curve; verifies system stability and reliable results

Standard

Pure substance of known composition and concentration used to prepare calibrators or assign values to control materials

Reference point for accuracy

Primary standard

A highly pure chemical that can be weighed or measured directly

e.g. anhydrous sodium chlored for chloride assays

Secondary standard

A solution standardized against a primary standard; used more routinely because it is stable and easier to prepare

Active errors

Errors committed by the frontline laboratory personnel during direct interaction with instruments, patients, or specimens

Occur at the “sharp end” of the system

Usually individual-level rather than systemic flaws

Latent errors

Hidden system weaknesses that create conditions for active errors to occur; organizational, procedural, or design flaws that may remain undetected

Occur at the “blunt end” of the system—management, policy, or workflow level

Often involve inadequate resources, unclear procedures, or poor safety culture

Pre-analytical phase / pre-examination phase

All activities from test ordering and patient preparation up to a specimen that is ready for analysis; controls the inputs to testing

Active errors in pre-analytical phase

Wrong patient/wrong label, wrong tube or QNS, inadequate mixing, hemolysis

Latent errors in pre-analytical phase

No barcode verification, ambiguous requisitions, inadequate staffing/layout

Analytical phase

All activities from loading an accepted specimen onto a validated method through generation verified analytical data

Governs measurement performance

Systemic error in analytical phase

miscalibration, deteriorated reagent lot, wrong blank

Random error in analytical phase

Pipetting bubbles, transient temperature/voltage fluctuation

Active error in analytical phase

overriding critical instrument flags

Latent error in analytical phase

Unclear SOPs, deferred maintenance, inadequate QC frequency

Post-analytical phase

All activities from analytical validation through result, reporting, communication, archiving, and follow-up

Controls the outputs to clinical decision-making

Active errors in the post-analytical phase

Wrong unit or reference interval, wrong patient result posted, delayed critical call

Latent errors in post analytical phase

No double-check policy, poorly configured auto-verification rules, inadequate TAT monitoring

Quality control

Refers to the system or set of procedures used to monitor the performance of analytical systems, detect errors, and maintain accuracy and precision of results

Internal quality control (IQC)

To ensure reliability within the laboratory on a daily basis

External quality control (proficiency testing / EQA)

To verify inter-laboratory compatibility and overall performance by testing standardized specimens from an external provider

Levey-Jennings chart

Plots QC results over time against the mean (x̄) and control limits (±1, ±2, ±3 SD)

Visualizes shifts (sudden change in mean) and trends (gradual drift)

Primary tool for daily QC monitoring

Westgard rules

Applies statistical decision rules to identify QC violations

Enhances error detection power and reduces false rejections

Youden plot (Two-control plot)

Compares two control levels (e.g., normal and high) on X-Y axes

Clusters indicate systemic bias; scattered points show random errors

External QC/PT reviews; reagent lot crossover

Cusum (Cumulative sum) chart

Tracks cumulative derivation from target mean

Detects subtle trends earlier than Levey-Jennings charts

Low-sigma methods; critical analytes needing tight drift control