1. Quality Control Lecture 5
Quality Assurance
Quality Control
Lecture 5

2. 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

3. 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

4. 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

5. 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

6. 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

7. Characteristics of A Good Control
The composition of the control material should be as similar to the patient sample as possible, reacting in the same manner
The analyte concentration should be at medically significant levels
The constituents should be stable under storage for a long period of time prior to preparation
Material should have low vial-to-vial variability
The material should be ready to use or require a minimum of preparation and be readily available for emergency use
After a vial has been opened and the material prepared, it should remain stable for the period of use
The material should be available in large quantities
The material should be reasonably priced (but cost should not be the primary factor)

8. 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

9. 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
coefficient of variation: It is defined as the ratio of the standard deviation to the mean .

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

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

17. 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