QUALITY ASSURANCEQuality Control

Lecture 5

What is Quality Control?

• Quality Control in the clinical laboratory is a system designed to increase the probability that:• each result reported by the laboratory is valid• and can be used with confidence by the physician to make a diagnostic or therapeutic decision

Internal Quality control• Internal quality control involves the analysis of control

samples with patient specimens, then evaluating the results statistically to determine the acceptability of the analytical run

• They are used to analyze the accuracy and precision performance of the assay or analyzer

• If the control is in range, it is assumed that the reagents and analyzer are performing correctly and patient testing can begin

• When control samples do not produce accurate and precise results, it can be assumed that any patient results obtained at the same time are also erroneous

Control• A solution that contains the same constituents as those being analyzed in the patient sample

• Most are commercially produced from pooled sera

• The manufacturer has analyzed each lot of serum for a variety of test components and the expected range of assay values for each component is provided to the laboratory when shipped

Internal Quality Control

• For the Internal Quality Control, the preparation of the control samples and their interpretation are handled within the laboratory

• In contrast, External quality control involves the estimation of a test method's accuracy by the analysis of unknown samples sent to the laboratory from outside sources

• The samples are sent to the laboratory where they are analyzed and the results returned to the agency that supplied the control

Calibrators• Controls and calibrators or standards differ; and are not

interchangeable• Calibrators and standards are used to adjust instrumentation or to

define a "standard curve" for analysis• The value assigned for each constituent are to be determined by a

reference method

• Definitions• The set of operations that establish, under specified

conditions, the relationship between values indicated by a measuring instrument and the corresponding values of the analyte to be measured

• Calibrators are solutions with known values that establish the relationship between the amount of signal produced in the assay and analyte concentration

Characteristics of A Good Control1. The composition of the control material should be as similar to

the patient sample as possible, reacting in the same manner

2. The analyte concentration should be at medically significant levels

3. The constituents should be stable under storage for a long period of time prior to preparation

4. Material should have low vial-to-vial variability

5. The material should be ready to use or require a minimum of preparation and be readily available for emergency use

6. After a vial has been opened and the material prepared, it should remain stable for the period of use

7. The material should be available in large quantities

8. The material should be reasonably priced (but cost should not be the primary factor)

Qualitative "bipolar" and Semi-Quantitative Procedures

• No entirely satisfactory statistical evaluation• Control levels should consist of a minimum of a negative

and weak positive control• A strong positive control is useful in monitoring the

sensitivity of the method in the upper range but is not always necessary

• The control is used as a point of reference from which the technologist makes a judgment for comparison

• Semi quantitative tests should have control concentrations at each of the graded levels, that is, trace, 1 +, 2+, and so on

• As with the qualitative methods, each control level can be used as a comparison for grading the test results

Quantitative Procedures• In quantitative procedures, commercially prepared quality control sera are used with patient samples to detect systematic analytical errors and monitor precision

• Prepare and test the material daily for a minimum of 20 consecutive working days, paying careful attention to instrument function

• At the end of 20- day period all of the data is collected to calculate a mean, standard deviation, and coefficient of variation excluding the data known to be the result of mistakes and explained errors

Quantitative Procedures• The distribution of data set should be a bell-shaped

Gaussian curve• If the data distribution is skewed, some sort of large

systematic shift has occurred during the test period and the data should not be used to calculate the control's acceptable limits

• Investigate possible problems and restart data collection• Control sample placement should be random within the

analytical run to estimate more accurately the amount of imprecision

• Sometimes controls are analyzed at fixed intervals • e.g. every 20 samples

Interpretation

• Interpretation of the control result can take one of several forms: • Graphical interpretation using levey-Jennings or

shewhart charts• Statistical and graphical interpretation by:

• multi-rules, • cumulative summaries • and trend analysis

Shewhart or Levey- Jennings control charts

• The levey-Jennings control chart is derived from the Gaussian distribution indicating the mean and the one, two, and three standard deviation ranges on both sides of the mean

• The chart illustrates the relationship between the levey-Jennings control chart and the Gaussian distribution from which it is derived

• This figure also shows the expected percentage of results that should fall within each of the standard deviation ranges

Shewhart or Levey- Jennings control charts

• On the control chart used to evaluate the result of the control runs• the dates or number of analyses are listed along the X-axis • and the values of the control along the Y- axis

• The mean and the 1,2 and 3 standard deviation (s) limits of the control analysis to date are marked

• As data is obtained it is plotted one point at a time along the chart

Shewhart or Levey- Jennings control charts

• In a random distribution and in a correctly operating test system approximately: • 65% of the values will be

between the ± Is ranges and will be evenly distributed on either side of the mean

• 95% of the values should fall between the ± 2s ranges

• and 99% between the ± 3s limits

Shewhart or Levey- Jennings control charts

• The ± 2s limits are considered as warning limits• A value between the 2s and 3s limit indicates the analysis

should be repeated• The ± 3s limits are rejection limits. Analysis should stop,

patient results held and the test system investigated

• Example of a shift in calibration can be failure in recalibration when lot numbers of reagents during analytical run

• A trend can start on one side of the mean and move across it or it can occur entirely on one side of the mean

• Trends can be caused by the deterioration of reagents, pump tubing or light sources in instruments

• Shifts and trends can occur together or independently