MLS 407 | Introduction to Quality Control

Quality management system

Coordinated activities to direct and control an organization with regard to quality

Definition used by ISO and CLSI

All aspects of the laboratory operation needs to be addressed to assure quality

Process control

An essential element of the quality management system; refers to control of the activities employed in the handling of samples and examination processes in order to ensure accurate and reliable testing

Sample management and all QC processes are part of this

QC monitors what?

activities related to the examination (analytic) phase of testing

What is the goal of QC?

To detect, evaluate, and correct errors due to test system failure, environmental conditions or operator performance, before results are reported

What is QC?

the part of quality management focused on fulfilling quality requirements

part of QA

it is examining “control” materials of known substances along with patient samples to monitor the accuracy and precision of the complete analytic process. QC is required for accreditation purposes.

internal quality control (IQC)

a set of procedures for continuously assessing laboratory work and the emergent results

Quantitative Examinations

measure the quantity of an analyte present in the sample, and measurements need to be accurate and precise. The measurement produces a numeric value as an end-point, expressed in a particular unit of measurement.

Qualitative examinations

those that measure the presence or absence of a substance, or evaluate cellular characteristics such as morphology. The results are not expressed in numerical terms, but in qualitative terms

Semiquantitative examinations

s are similar to qualitative examinations, in that the results are not expressed in quantitative terms. The difference is that results of these tests are expressed as an estimate of how much of the measured substance is present. Results might be expressed in terms such as “trace amount”, “moderate amount”, or “1+, 2+, or 3+”

Examples are urine dipsticks, tablet tests for ketones and some serologic agglutination procedures. In the case of other serologic testing, the result is often expressed as a titre—again involving a number but providing an estimate,

Controls

substances that contain an established amount of the substance being tested—the analyte.

Controls are tested at the same time and in the same way as patient samples.

The purpose of the control is to validate the reliability of the test system and evaluate the operator’s performance and environmental conditions that might impact results.

Calibrators (Standards)

Solutions with a specified defined concentration that are used to set or calibrate an instrument, kit, or system before testing is begun. Calibrators are often provided by the manufacturer of an instrument. They should not be used as controls since they are used to set the instrument

Characteristics of control materials

It’s critical to select the appropriate control materials.

Some important characteristics to consider when making the selection are:

• Controls must be appropriate for the targeted diagnostic test—the substance being measured in the test must be present in the control in a measurable form.

• The amount of the analyte present in the controls should be close to the medical decision points of the test; this means that controls should check both low values and high values.

• Controls should have the same matrix as patient samples; this usually means that the controls are serum based, but they may also be based on plasma, urine or other materials.

Types and sources of control material

• They may be frozen, freezedried or chemically preserved.

  • The freeze-dried or lyophilized materials must be reconstituted, requiring great care in pipetting in order to ensure the correct concentration of the analyte.

• Control materials may be purchased, obtained from a central or reference laboratory, or made in-house by pooling sera from different patients.

• Purchased controls may be either assayed or unassayed. Assayed controls have a predetermined target value, established by the manufacturer.

• When using assayed controls, the laboratory must verify the value using its own methods.

• Assayed controls are more expensive to purchase than unassayed controls.

• When using either unassayed or “in-house” controls, the laboratory must establish the target value of the analyte.

Establishing the value range for the control material

• Once the appropriate control materials are purchased or prepared, the next step is to determine the range of acceptable values for the control material.

• This will be used to let the laboratory know if the test run is “in control” or if the control values are not reading properly—“out of control”.

• This is done by assaying the control material repeatedly over time. At least 20 data points must be collected over a 20–30-day period.

• When collecting this data, be sure to include any procedural variation that occurs in the daily runs; for example, if different testing personnel normally do the analysis, all of them should collect part of the data.

• Once the data is collected, the laboratory will need to calculate the mean and standard deviation of the results.

• A characteristic of repeated measurements is that there is a degree of variation.

• Variation may be due to operator technique, environmental conditions or the performance characteristics of an instrument. Some variation is normal, even when all of the factors listed above are controlled. The standard deviation gives a measure of the variation. This process is illustrated below.

The _____ of repeated measurements will be distributed around a central point or location. This characteristic of repeated measurements is known as ____ ___

variability; central tendency

Accuracy

closeness of a measurement to its true value

Precision

the amount of variation in the measurements.

• The less variation a set of measurements has, the more precise it is.

• In more precise measurements, the width of the curve is smaller because the measurements are all closer to the mean.

Bias

• the difference between the expectation of a test result and an accepted reference method.

• The reliability of a method is judged in terms of accuracy and precision.

Laboratory Quality Includes

• Accuracy

• Reliability

• Timeliness

Quality System Essentials

1. Organization

2. Personnel

3. Equipment

4. Purchasing and inventory

5. Process control

6. Info management

7. Doc and records

8. Occurrence management

9. Assessment

10. Process improvement

11. Customer service

12. Facilities and safety

QA

• part of quality management

• provides confidence in lab

• pre-examination

• examination

• post-examination

• focused on workflow path

Difference between QC vs QA

Typically, QA activities and responsibilities cover virtually all of the quality system in one fashion or another, while QC is a subset of the QA activities. Also, elements in the quality system might not be specifically covered by QA/QC activities and responsibilities but may involve QA and QC.

Mean

arithmetic average of results. most commonly used measure of central tendency used in lab QC

Mode

number that occurs most frequently

Median

central point of values when arranged in numerical order

Standard deviation

a measurement of variation in a set of results. useful for analyzing QC results

the average ‘distance’ each data point in a normal distribution pattern is from the mean

Limitation: valid for normal distribution; magnitude of the SD is influenced by mean value; influenced by outliers

Coefficient of variation

the SD expressed as a percentage of the mean

SD/Mean x 100 = CV (%)

Helps us see that even a lower SD value may not mean less variability of data

takes the magnitude of mean awa

T/F: It is desirable to have the control data to show a slim distribution about the mean

True

What happens when comparing both sets of data that have the same mean?

You can use SD of each data set for more detailed results

Low vs high %CV values

• Low = small amount of variability; high reproducibility; precise

• High = large amount of variability, low reproducibility; imprecise

What does “out of control” mean?

When the QC sample that is used in a test run is out of the acceptable range

Levey-Jennings Charts

Charts that use a series of horizontal lines to represent each SD range and the mean value

Quality Control Specimens

are analyzed to monitor the performance of a test or process

Control values within acceptable limits (mean+ 2SD) verify validity of assay

Common laboratory practice to include at least 2 levels of control for each assay

• Level 1, normal control

• Level 2, abnormal control

Lot number

an identification number assigned to a particular (qty/lot/batch)of materials

• enables tracking of the materials and may be used to recall a particular cohort of product

• date of manufacture

• batch produced that day

What Are Built-In Controls?

Built-in controls (also called internal controls) are controls that are already incorporated into a test system. They are designed to verify that the test procedure worked correctly without requiring additional materials.

Why Are Built-In Controls Important?

Built-in controls help ensure that:

• The test system is functioning properly

• Reagents are working as expected

• The sample has migrated or reacted correctly

• The test conditions were adequate

If the built-in control does not perform as expected, the test result is invalid

Purpose of External Liquid Controls

External liquid quality control samples are used to:

• Verify the test system can accurately detect the analyte of interest

• Identify potential reagent issues or equipment failures

• Confirm overall test system performance prior to patient testing

Even if a test kit includes built-in control, external liquid controls must be performed first and be acceptable before patient testing can be begin.

Built-in controls confirm that a test ran ____ but external liquid controls verify that the test system is performing ____ and ____

correctly; accurately; reliably

What information is required on Levey-Jennings charts

• Test

• Method

• Units

• Month

• Control & lot #

• Date in use

• Date expires

• N (number of values)

• Mean

• SD

• CV

• MLS/tech

What do you record on the left side of LJ charts?

On the left side, record the mean value, typically centered on the y-axis

• Calculate and label the following ranges

  • ±1 SD

  • ±2 SD

  • ±3 SD

• Clearly mark these values above and below the mean on the chart

Parallel testing

running new and current QC at the same time; need at least 30+ data points for a new lot, current lot needs to be valid first to establish a new acceptable range

Outlier

RAE; a data point that falls either above +3SD or below +3SD (with two control levels)

Shift

SAE; when 6 or more data points suddenly shift directions towards/away from mean but cannot cross the mean

Trend

SAE; when 6 or more data points gradually go in one direction and can also cross the mean

2_2S Rule

SAE; when 2 consecutive values are between 2SD and 3SD. The second value is the one that is determined out of control; the first one is a warning

Random analytical error (RAE)

random outlier, usually happens once, affects precision

Systematic analytical error (SAE)

includes shifts, trends, and the 2-2s rule. A systematic error is system failure; casual/abrupt

List organizations that determine quality standards

FDA, CDC, CLSI, ISO, CAP, AABB

QC analysis can be used to monitor what?

• Analytic processes

• Instrument performance

• Reagent/media performance/stability

• Calibration verification

Non-normal distributions indicate

indicate presence of outliers/asymmetry, bias in data, reduced reliability of tests

State the percentage of values included in each of the following ranges:

        a.  Mean ± 1 SD:

        b.  Mean ± 2 SD:                        

        c. Mean ± 3 SD:

 

68%, 95%, 99.7%

What are appropriate QC mateirals?

Ones that mimic patient specimens as closely as possible

Differentiate the use of calibrators/standards from controls, describing an application of each in the clinical laboratory.

·         Calibrators/standards establish accuracy by setting the instrument response.

·         Controls monitor ongoing performance and reliability after calibration.

Explain the process of lot-to-lot reagent confirmation

the process of verifying that a new reagent lot performs equivalently to the current reagent lot before the new lot is placed into routine clinical use.

What causes outliers?

pipetting errors, air bubbles, environmental change 

What causes shifts?

new lot reagent, reagent prepared incorrectly, reagent reformulation, incorrect calibration, wrong values entered, instrument issues, probe malfunction, temp change, new lot QC or wrong preparation, operator error

What causes trends?

reagent deterioration, calibration drift, aging, wear