# Presentation: 064971

## Quality Control

**Chama Chisala **
**Dip MLT, HNC/MLS; AIBMS**

## The Quality System

**Information Management**

**The Quality System**

## The Quality Assurance Cycle

**The Quality Assurance Cycle**

- Pre-Analytic

- Analytic

- Post-Analytic

**Data and Lab Management**
**Safety**
**Customer Service**

- Patient/Client Prep
- Sample Collection

- Sample Receipt and Accessioning

- Sample Transport

- Quality Control

- Record Keeping

- Reporting

- Personnel Competency
- Test Evaluations

- Testing

## Quality Control

**Definitions**
**Qualitative Quality Control**
**Quantitative QC – How to implement**
**Selection and managing control materials**
**Analysis of QC data**
**Monitoring quality control data**

## 
Quality Assurance in Clinical or Pathology Laboratory is a term usually applied to analytical performance and it incorporates the activities of External Quality Assessment and Internal Quality Control. 

A Quality Control system is designed to ensure that individual patient sample measurements are within clinically acceptable limits.

**Quality Assurance in Clinical or Pathology Laboratory is a term usually applied to analytical performance and it incorporates the activities of External Quality Assessment and Internal Quality Control. **
**A Quality Control system is designed to ensure that individual patient sample measurements are within clinically acceptable limits.**

- What is Quality Control?

## Process or system for monitoring the quality of laboratory testing, and the accuracy and precision of results

Routinely collect and analyze data from every test run or procedure

Allows for  immediate corrective action

**Routinely collect and analyze data from every test run or procedure**
**Allows for  immediate corrective action**

## Designing a QC Program – 

**Establish written policies and procedures**
**Corrective action procedures**
**Train all staff**
**Design forms **
**Assure complete documentation and review**

## Qualitative vs.Quantitative

**Quantitative test **
**measures the amount of a substance present**
**Qualitative test**
**determines whether the substance being tested for is present or absent**

**Notes:**
Qualitative tests
Tests that do not have measurable endpoints, for example:
Growth-no growth
Positive-negative
Color change

## Qualitative QC

**Quality control is performed for both, system is somewhat different**
**Controls available****	**
**Blood Bank/Serology/Micro**
**RPR/TPHA**
**Dipstick technology**
**Pregnancy**

## Stains, Reagents, Antisera

**Label containers**
**contents**
**concentration**
**date prepared**
**placed in service**
**expiration date/shelf life**
**preparer**

## Media Preparation

**Record amount prepared**
**Source**
**Lot number**
**Sterilization method**
**Preparation date**
**Preparer**
**pH**
**Expiration date **

## Quality Control  Quantitative Tests

**How to implement a laboratory quality control program**

## Implementing a QC Program –Quantitative Tests

**Select high quality controls**
**Collect *****at least***** 20 control values over a period of 20-30days for each level of control**
**Perform statistical analysis**
**Develop Levey-Jennings chart **
**Monitor control values using the Levey-Jennings chart and/or Westgard rules **
**Take immediate corrective action, if needed**
**Record  actions taken **

**Notes:**
Monitor control values on a run-by-run basis using the Levey-Jennings chart and/or Westgard rules 

Develop Levey-Jennings chart using the calculated values for mean, SD, and range

## Selecting Control MaterialsCalibrators

**Has a known concentration of the substance (analyte) being measured **
**Used to adjust instrument, kit, test system in order to standardize the assay**
**Sometimes called a standard, although usually not a true standard **
**This is *****not***** a control**

##  Selecting Control Materials Controls

**Known concentration of the analyte**
**Use 2 or three levels of controls **
**Include with patient samples when performing a test**
**Used to validate reliability of the test system**

## Control MaterialsImportant Characteristics

**Values cover medical decision points  **
**Similar to the test specimen (matrix)**
**Available in large quantity**
**Stored in small aliquots**
**Ideally, should last for at least 1 year**
**Often use biological material, consider bio-hazardous**

**Notes:**
Values cover medical decision points – often use high and low, or normal and abnormal

## Managing Control Materials

**Sufficient material from same lot number or serum pool for one year’s testing**
**May be frozen, freeze-dried, or chemically preserved**
**Requires very accurate reconstitution if this step is necessary**
**Always store as recommended by manufacturer**

## Sources of QC Samples

**Appropriate diagnostic sample**
**Obtained from:**
** ****Another laboratory **
**EQA provider**
**Commercial product**

**Notes:**
1. QC Sample
The Sources of QC Samples
QC samples can be obtained from a number of different sources:
Producing your own external control  - requires resources because there are many validation and testing steps.  Can produce very large volumes with exact specifications.
Selecting a diagnostic sample - must meet QC sample requirements.  Cheaper option but difficult to get very large volumes so may have to change QC samples often.  This will inhibit the collection of longitudinal and batch to batch data.
Obtaining a QC sample form another laboratory - saves time, but does not guarantee a well standardised and validated product.  Collaboration between laboratories assists in providing the large volume required and may decrease costs. 
Samples provided as participation in an External QC Programme -this is the preferable option as it provides follow up and feedback on your performance in comparison to other laboratories. 
Commercially available controls - e.g. BBI Accurun (Boston Biomedica Inc) are purchased by the millilitre and are expensive.  Samples are ‘stand alone’ because no results are collected and no feedback is provided.  BBI Accurun is a very stable sample due to its production process which involves heat treatment.  Because of this the sample is not as sensitive to small fluctuations and may only identify large shifts in variation shifts, similar to the positive control. 

## Types of Control Materials

**Assayed**
**mean calculated by the manufacturer**
**must verify in the laboratory**
**Unassayed**
**less expensive**
**must perform data analysis**
**“****Homemade” or “In-house” **
**pooled sera collected in the laboratory**
**characterized**
**preserved in small quantities for daily use**

## Storage of QC Samples 

**Validated batch aliquoted into smaller ‘user friendly’ volumes for storage**
**Establish a storage protocol:**
**store at -20****o****C**
**in use vials stored at 4****o****C**
**use 0.5 ml vial maximum of one week**
**freeze-dried **
**(requires accurate reconstitution)**
**chemically preserved**

**Notes:**
1.3 Method of QC Production 
1.3.6 Storing QC Samples
The QC sample is dispensed into labelled aliquot's of a smaller ‘user friendly’ volume. 
Aliquot's in use can be stored at 4C.  These should be discarded after 7 days and a new 1ml vial introduced. 
By aliqoting the sample into 1ml volumes all but the QC sample in use can be stored at -20C.  This prevents freeze thawing which can affect the QC sample result.  
1ml aliquot's can be sub-aliquoted if  the 1ml volume will not be exhausted in a week.
The label on the QC Sample should include the name of the QC Sample, and may include the expiry date (usually 12 months from the date of production) and the production laboratory’s initials.

## Slide 21

## Quality Control -Quantitative

**Analysis of QC Data**

## How to carry out this analysis?

**Need tools for data management and analysis**
**Basic statistics skills**
**Manual methods**
**Graph paper**
**Calculator**
**	****Computer helpful**
**Spreadsheet**
**Important skills for laboratory personnel**

## Analysis of Control Materials

**Need data set of at least 20 points, obtained over a 30 day period**
**Calculate mean, standard deviation, coefficient of variation; determine target ranges**
**Develop Levey-Jennings charts, plot results**

## Establishing Control Ranges

**Select appropriate controls**
**Assay them repeatedly over time **
**at least 20 data points**
**Make sure any procedural variation is represented: **
**different operators**
**different times of day**
**Determine the degree of variability in the data to establish acceptable range**

## Measurement of Variability

**A certain amount of variability will naturally occur when a control is tested repeatedly.**
**Variability is affected by operator technique, environmental conditions, and the performance characteristics of the assay method.**
**The goal is to differentiate between variability due to chance from that due to error.**

## Measures of Central Tendency

**Data are frequently distributed about a central value or a central location**
**There are several terms to describe that central location, or the ‘central tendency’ of a set of data**

## Measures of Central Tendency

**Median ****= the value at the center (midpoint) of the observations**
**Mode ****= the value which occurs with the greatest frequency**
**Mean ****= the calculated average of the values**

## Calculation of Mean:  Outliers

**192 mg/dL**
**194 mg/dL**
**196 mg/dL**
**196 mg/dL**
- 160 mg/dL
**196 mg/dL**

**200 mg/dL**
**200 mg/dL**
**202 mg/dL**
- 255 mg/dL
**204 mg/dL**
**208 mg/dL**
**212 mg/dL**

## Calculation of Mean

**192 mg/dL**
**194 mg/dL**
**196 mg/dL**
**196 mg/dL**
**196 mg/dL**
**200 mg/dL**
**200 mg/dL**
**202 mg/dL**
**204 mg/dL**
**208 mg/dL**
**212 mg/dL**
**Sum = 2,200 mg/dL**

**Mean**** = the calculated average of the values**
**The sum of the values (X****1 ****+ X****2**** + X****3**** ... X****11****) divided by the number (n) of observations**
**The mean of these 11 observations is (2200 ******** 11) = ****200 mg/dL**

## Normal Distribution

**All values are symmetrically distributed around the mean**
**Characteristic “bell-shaped” curve**
**Assumed for all quality control statistics**

## Normal Distribution

**Frequency**

**	****4.7’****	****4.8’****	****4.9’****	****Mean****	****5.1’****	****5.2’****	****5.3’**

## Normal Distribution

- Mean

## Accuracy and Precision

**The degree of fluctuation in the measurements is indicative of the “precision” of the assay.**
**The closeness of measurements  to the true value is indicative of the “accuracy” of the assay.**
**Quality Control is used to monitor both the precision and the accuracy of the assay in order to provide reliable results.**

## Precision and Accuracy

**Precise and accurate**

## Imprecise and  inaccurate

## Measures of Dispersion or Variability

**There are several terms that describe the dispersion or variability of the data around the mean:**
**Range**
**Variance**
**Standard Deviation**
**Coefficient of Variation**

## Calculation of Standard Deviation 

## Calculation of Standard Deviation

**The standard deviation (SD) is the square root of the variance**
**it is the square root of the average squared deviation from the mean**
**SD is commonly used (rather than the variance) since it has the same units as the mean and the original observations**
**SD is the principle calculation used in the laboratory to measure dispersion of a group of values around a mean**

## Standard Deviation and Probability

**For a set of data with a normal distribution, a value will fall within a range of:**
**+/- 1 SD 68.2% of the time**
**+/- 2 SD 95.5% of the time**
**+/- 3 SD 99.7% of the time**

## Standard Deviation and Probability

**In general, laboratories use the +/- 2 SD criteria for the limits of  the acceptable range for a test**
**When the QC measurement falls within that range, there is 95.5% confidence  that the measurement is correct**
**Only  4.5% of the time will a value fall outside of that range due to chance; more likely it will be due to error**

## Calculation of Coefficient of Variation

**The coefficient of variation (CV) is the standard deviation (SD) expressed as a percentage of the mean**
**Ideally should be less than 5%**

## Monitoring QC Data

## Monitoring QC Data

**Use Levey-Jennings chart**
**Plot control values each run, make decision regarding acceptability of run**
**Monitor over time to evaluate the precision and accuracy of repeated measurements**
**Review charts at defined intervals, take necessary action, and document **

## Levey-Jennings Chart

**A graphical method for displaying control results and evaluating whether a procedure is in-control or out-of-control**
**Control values are plotted versus time **
**Lines are drawn from point to point to accent any trends, shifts, or random excursions**

## Levey-Jennings Chart

## Levey-Jennings Chart - Record Time on X-Axis and the Control Values on Y-Axis

- Time (e.g. day, date, run number)

## Levey-Jennings Chart -Plot Control Values for Each Run

- Time (e.g. day, date, run number)

## Levey-Jennings Chart Calculate the Mean and Standard Deviation;Record the Mean and +/- 1,2 and 3 SD Control Limits

- Mean

- Day

- +1SD

- +2SD

- +3SD

- -1SD

- -2SD

- -3SD

## Levey-Jennings Chart -Record and Evaluate the Control Values

- Mean

- Day

- +1SD

- +2SD

- +3SD

- -1SD

- -2SD

- -3SD

## Findings Over Time

**Ideally should have control values clustered about the mean (+/-2 SD) with little variation in the upward or downward direction**
**Imprecision = large amount of scatter about the mean.  Usually caused by errors in technique**
**Inaccuracy = may see as a trend or a shift, usually caused by change in the testing process**
**Random error = no pattern. Usually poor technique, malfunctioning equipment**

## When does the Control Value Indicate a Problem?

**Consider using Westgard Control Rules**
**Uses premise that 95.5% of control values should fall within ±2SD**
**Commonly applied when two levels of control are used**
**Use in a sequential fashion**

## Westgard Rules

**“****Multirule Quality Control” **
**Uses a combination of decision criteria or control rules**
**Allows determination of whether an analytical run is “in-control” or “out-of-control”**

## Westgard Rules (Generally used where 2 levels of control material are analyzed per run)

**1****2S**** rule**
**1****3S**** rule**
**2****2S**** rule**

**R****4S**** rule**
**4****1S**** rule**
**10****X**** rule**

## Westgard – 12S Rule

**“****warning rule”**
**One of two control results falls outside ±2SD**
**Alerts tech to possible problems**
**Not cause for rejecting a run**
**Must then evaluate the 1****3S ****rule**

## 12S Rule = A warning to trigger careful inspection of the control data

- Mean

- Day

- +1SD

- +2SD

- +3SD

- -1SD

- -2SD

- -3SD

- 12S rule violation

## Westgard – 13S Rule

**If either of the two control results falls outside of ±3SD, rule is violated**
**Run must be rejected**
**If 1****3S**** not violated, check 2****2S**

## 13S Rule = Reject the run when a single control measurement exceeds the +3SD or -3SD control limit

- Mean

- Day

- +1SD

- +2SD

- +3SD

- -1SD

- -2SD

- -3SD

- 13S rule violation

## Westgard – 22S Rule

**2 consecutive control values for the same level fall outside of ±2SD in the same direction, or**
**Both controls in the same run exceed ±2SD **
**Patient results cannot be reported**
**Requires corrective action**

## 22S Rule = Reject the run when 2 consecutive control measurements exceed the same +2SD or -2SD control limit

- Mean

- Day

- +1SD

- +2SD

- +3SD

- -1SD

- -2SD

- -3SD

- 22S rule violation

## When a rule is violated

**Warning rule = use other rules to inspect the control points**
**Rejection rule = “out of control”**
**Stop testing**
**Identify and correct problem**
**Repeat testing on patient samples and controls **
**Do not report patient results until problem is solved and controls indicate proper performance**

## Solving “out-of-control” problems

**Policies and procedures for remedial action**
**Troubleshooting**

## Summary

**Why QC program?**
**Validates test accuracy and reliability**

## Summary: How to implement a QC program?

**Establish written policies and procedures**
**Assign responsibility for monitoring and reviewing **
**Train staff**
**Obtain control materials**
**Collect data**
**Set target values (mean, SD)**
**Establish Levey-Jennings charts**
**Routinely plot control data**
**Establish and implement troubleshooting and corrective action protocols**
**Establish and maintain system for documentation**