Mohd Jokha bin Yahya MSc (Mgt), BSc (Hons)

Unit Kualiti / Patologi Kimia Jabatan Patologi

Hospital Kuala Lumpur 29 September 2015

Basic Internal Quality Control

Institute Medical Research

QUALITY… AT A GLANCE

(Hammerling, 2012)

Interfaces or Manual data entry

Laboratory testing processes

Internal QC Accept/Reject

EQA data transfer

EQA Data Analysis

IQC Planning And Design

Inservice training

Validation tools

Documentation Validation Reports, Peer Reports

Toubleshooting

Inventory, ordering

Production, shipping Supplies & materials

Internet Support Services

A Total Quality Control Support System that integrate IQC and EQA

James O Westgard Internal quality control: planning and implementation strategies Ann Clin Biochem 2003; 40: 593–611

• TQM – quality management framework

Quality laboratory processes

Quality Control

Quality Improvement

Quality Planning

Why Statistical Quality Control (SQC) important?

With proper setting of control limit, (number of measurement and run), SQC can:

1. Ensure the quality of the tests results

2. Monitor the analytical performance and

alert the analysts to the problems that

occurred.

Important Functions of Internal QC:

1. Provides immediate accept/reject criteria for a set of analytical data (a “run")

2. Provides a long term record of analytical performance

3. Usually monitors performance at multiple concentration levels

Implementation of Internal Quality Control

1. Selection of suitability QC materials

2. Establish control ranges for selected materials

3. Develop graphs to plot control values

4. Establish policies & procedures (SOP)

5. Assign responsibility for monitoring & review of QC

IMPLEMENTATION OF QUALITY CONTROL

6. Understanding of QC procedures by staff

7. Establish a system for monitoring control values

8. Take immediate corrective action when QC is unacceptable

9. Maintain records of QC results & corrective action taken in response to QC results

1. Select control materials • Similar to patients sample

• Homogenous and stable

• Acceptable shelf life

• Multiple levels (medical decision levels)

• Have good open vial stability

• Be safe from infectious disease

1.The calculations

2.Collect at least 20 data from 20 different days

Mean, SD, CV, Control Limits & SDIs,

what they are and how to calculate them.

2. Establish control ranges for selected materials

Normal Distribution

Mean

SD = Standard Deviation

The Actual

Calculating Mean

∑Xi = summation of observation to i n = number of observation

The mean is define as the arithmetic average of a set of data points.

STANDARD DEVIATION (SD)

The standard deviation (SD) quantifies the degree of dispersion of data point about the mean and is used to set limits upon which control result acceptibility is determined.

Coefficient of Variance

The unit is in percentage (%)

CV = SD/mean X 100

The coefficient variation (CV) is a measure of variability.

The degree of replication or reproducibility.

The CV is useful for comparisons of precision.

QC : The calculations

Procedure for calculating Average & SD

1. Record control analyses.

2. Add column “Measured Value”.

3. Calculate average.

4. Calculate & record individual difference from average.

5. Square each individual difference, & record.

6. Add column

7. Calculate SD.

Guide for Data Collection • Derived from package insert

• What is the % CV indicated?

Example:

2.9-2.1 = 0.8

0.8 / 6 = 0.13

(0.13/2.5)x100

CV% = 5.3%

Example:

2.9-2.1 = 0.8

0.8 / 4 = 0.2

(0.2/2.5)x100

CV% = 8%

Control Limit

•A line drawn on a control chart for displaying control results and evaluating a measurement is in-control or out of control

•Normally, it calculated from Mean and SD from a given control material

3. Develop graphs to plot control values

Levy-Jennings Plots

Graphically time versus value chart

3SD

2SD

1SD

-3SD

-2SD

1SD

Mean

Time

QC - Goals • Ensure lab reports reliable & valid

• Both accurate and precise

• Predict patient-sample accuracy

• Rely on statistical principles • Should I report patient test results?

4. Establish policies & procedures (SOP)

Quality Control procedure

• The operational techniques and activities that are used to fulfill requirement for quality in the aspect of test method and system performance

Testing control materials

Charting and analysing control results Identify sources of error

Evaluating

Document all the remedial action

• The “true” value of the constituent. • Presented in bias – usually observed from external QC

• Degree of deviation from the true value

Accuracy

Statistical Process Control Use Levey-Jennings graphs

Use statistical rules on SD

A set of rules that use statistic to monitor and evaluate a process.

differentiate analytical errors & mistakes from normal fluctuations “statistical errors”

Concept of “early warning”

Predict based on control results & statistical principles whether system has changed (analytical error)

The system used improperly (mistake)

Based on this, we infer reliability of a patient sample value.

History of Westgard rules

Published by Dr. James Westgard (University of Wisconsin) in 1981

(Clin. Chem. 27/3, 493-501)

Elements of Westgard system is based on principles of Statistic Process Control (SPC) used in industry nationwide (US).

(Walter A. Shewhart)

Objective of Westgard rules

• To provide simple data analysis and display via control chart

• To improve the capability of analytical errors detection with low level of false rejection (Pfr)

• To provide some indication of type of error, to aid in problem solving in clinical laboratories testing

Levey Jennings Chart

Single rule procedure;

1SD – 32% high false rejection rate, better error detection

2SD – 5% false rejection rate,(false alarm problem)

3SD - 1% false rejection rate – low error detection (true alarm)

Westgard rules

•A set of 6 statistical rules with multiple applications when used separately or in concert with each other are used to verify the reliability for patient test results.

• The control procedure recommended here is for application where a stable control are available and are analysed repeatedly over long period of time

Run

•Defined by CLIA as an interval within which the accuracy and precision of a testing system is expected to be stable but cannot be greater than 24 hours or less than the frequency recommended by the manufacturer

•Analytical run

12s

12s refers to the control rule that is commonly used with a Levey-Jennings chart when the control limits are set as the mean plus/minus 2s. In the original Westgard multirule QC procedure, this rule is used as a warning rule to trigger careful inspection of the control data by the following rejection rules.

13s (within run only)

13s refers to a control rule that is commonly used with a Levey-Jennings chart when the control limits are set as the mean plus 3s and the mean minus 3s. A run is rejected when a single control measurement exceeds the mean +3s or the mean -3s control limit. Adapted from Biorad

22s (across runs)

22s – the rules is violated across runs when the previous value for a particular control level exceeds the “same” (mean +2s) or (mean –2s) limit.

Adapted from Biorad

22s (within the runs)

22s – the rules is violated within the run when 2 consecutive control values exceed the “same” mean +2s or the -2s control limit.

Adapted from Biorad

R4s

R4s – Reject when 1 control measurement in a group exceeds the mean +2s and another exceeds the mean –2s

Adapted from Biorad

41s (across and within control materials)

41s – the rule is violated within the control materials when the last 4 controls values of the same control level exceed the same mean +1s or the same mean -1s limit. The rule is violated across the controls materials when the last 4 consecutive control values for different levels exceed the same mean +1s or the same mean -1s limit. This rules may not require rejection of the run. Rather, it can be an indicator to perform instrument maintenance and/or calibration

Adapted from Biorad

10x (within and across control materials)

10x – the rule is violated within the control material when the last 10 consecutive values for the same control level are all on the same side of the mean. The rule is violated across the control materials when the last 10 consecutive values, regardless of the control level, are on the same side of the mean.

Can be modified to 9x (3 control levels) and 8x (4 controls levels)

Adapted from Biorad

Control

Data

12s

13

s

22s R4s 41s 10x

Out-of-Control, Reject analytical Run

In-Control, Report Result

Yes

No

Yes

No

No No No

No

Yes Yes

Yes Yes

Westgard Rules – QC

Multiple Procedures

Adapted from Biorad

ERRORS IN QUALITY CONTROL

• RANDOM ERRORS : ANY DEVIATION AWAY FROM THE EXPECTED RESULT EITHER NEGATIVE OR POSITIVE , WHOSE DIRECTION OR MAGNITUDE IN UNPREDICTABLE

• Any error that be either positive or negative , the direction and exact magnitude of which is unpredictable.

• Example of random error

Imprecision

Caused by unknown reason

Shows no specific pattern

May not be able to recover or correct

• SYSTEMATIC ERRORS : ERROR ALWAYS IN ONE DIRECTION CAUSING A CHANGE IN THE MEAN OF THE CONTROL VALUES

• An error that is always in one direction and is predictable

2 types : Shift & Trend

TREND : indicates gradual loss of reliability in the test system

SHIFT : sudden and dramatic change in the control mean either positive or negative

Adapted from Biorad

CAUSES OF Random Error

Power supply

Air bubbles in water supply

Random air bubbles in reagent or sample

Double pipetting of sample/reagent

Misplacement of control sample within a run

Incorrect reconstitution of controls

Operator technique : GLP

CAUSES OF TRENDS

Aging of reagent

Gradual deterioration of controls

Gradual deterioration of incubation temp.

Gradual deterioration of light filter integrity

Deterioration of instrument light source

Gradual accumulation of debris on electrode surface / sample / reagent tubing

CAUSES OF SHIFTS

Sudden change / failure in light source

Change in reagent formulation

Change in reagent lot

Major instrument maintenance

Sudden change in incubation temperature

Inaccurate calibration

Failure in sampling , reagent dispense system

Change in room temperature or humidity

Also The out-of-control problem

• Review procedures used

• Search for recent events that could cause change • New reagent kit or lot

• Calibration lot

• Instrumentation component replacement

• Instrumentation maintenance

• Instrument moved.

• Examine the environment conditions • temperature, humidity

• Prepare new control materials

• Follow manufacturers trouble-shooting guide

• Contact manufacturers of • Instrumentation / reagents

• Calibrator materials

• Control materials

“True” picture?

99.9% of values are within + 1SD

SD used is not “true”

This will caused reduce true error detection.

True Chart

5% of points supposed to be more than + 2SD

1 out of 20 points

Only 68% of the points supposed to be within +1SD

Package insert range

How to establish own range? • Run current control to ensure that system is

producing valid results

• Run new control material as per patient

• Repeat as per control procedure

• Collect at least 20 data points

• Cross over data used to calculate new lots mean and acceptable range

Current Lot

New Lot Cross Over

5. Assign responsibility for monitoring & review of QC

•Personnel or supervisor must review IQC data to detect problems and evaluate trends

• The IQC results should be verified for acceptability for reporting patient results

Monitoring

• The laboratory in-charge or designated personnel must review QC data on a monthly basis to assess the precision and accuracy

• Controls should also be run prior to patient testing after a change of analytical reagents, major preventive maintenance or a change of critical instrument component

6. Understanding of QC procedures by staff

Understanding of QC

Procedure

Training

Practice with supervision

Competency Assessment

Practice independently

Run QC for each batch

• Checklist of QC materials

• QC materials must be in good condition

QC Results

• Interprate by senior

• To accept or to reject run

Corrective Action

• Immediate action

• Record

7. Establish a system for monitoring control values

•All corrective action must taken immediately

•Affects patients safety

•Non-economical

8. Take immediate corrective action when QC is unacceptable

•Keep track

•Burden of proof

•To learn from mistakes

•To be reviewed

•Educational

•Accreditation / Proficiency

9. Maintain records of QC results & corrective action taken in response to QC results

•All individual data values

• Summary statistics – monthly and cumulative

•QC problems and decisions ( accept, reject, overrides)

• Trouble-shooting activities

•Corrective actions and follow ups

•Proficiency testing results

Every QC records should include ALL of the following information:

QC Tools

•Various tools are available

•Operating Specification Chart

• Sigma Matrix Chart

• Six Sigma

Advance Internal Quality Control

What not to do?

• Don’t use 2SD control limits

• Don’t just repeat the controls

• Don’t use the same control rules for all tests

• Don’t use bottle values to calculate control limits

• Don’t use medical decision limits as control limits

• Don’t rely on electronic QC alone

• Don’t eliminate SQC in POC applications

Thank You