Basics of QC

WelcomeBasics of Quality Controls

Rajiv Gandhi University of Health and Sciences

10-04-09

• A control is a “Patient-Like” sample composed of one or many constituents whose concentrations are known. The constituent or analyte concentrations are represented by a range of acceptable values with upper and lower limits. Controls are used to monitor the precision and accuracy of the diagnostic testing system.

• When the observed control values fall within the acceptable range, the laboratories can confirm the test system is working properly and the patient results can be reported with confidence.

What is a Control?What is a Control?

Why do we do QC testing?Precision Testing

Determination of Relative Bias

Objectives

Quality Controls and Regulatory Standards

• Quality Council Of India ( QCI ) : Essential Standards for Registration of Medical Testing Laboratories In India

- 3.5.2 : Medical Laboratories shall perform internal Quality Control . Use of third party human matrix quality control is recommended for all analytes .Laboratories are encouraged to participate in interlab comparisons / External Quality Assessment Schemes EQAS/ Proficiency Testing (PT).

• ISO 15189 Medical Laboratories-Particular requirements for quality and competence– 5.6.1 “The laboratory shall design internal quality control

systems that verify the attainment of the intended quality of results.”

– 5.6.3 “…other means of providing confidence in the results shall be applied, including but not limited to the following: a) participation in a suitable programme of interlaboratory comparisons…”



Clinical Laboratory Improvement Act (CLIA)

• Laboratories must test controls at prescribed intervals

• At least two different concentrations of controls should be tested

• Laboratories must have established criteria for acceptable QC

• Laboratories are responsible for the quality of testing

Quality Controls:Important Characteristics

• Unbiased Assessment or Third Party• Long Shelf-Life and Open Vial Stability• Clinically Relevant Levels• Human Based Matrix• Extensive Assayed Values Provided• Comprehensive Range of Products

“In-kit control” = “Manufacturer’s control”

Supplied with test kit or by the manufacturer of the laboratory’s instrument

In-Kit Controls: Can problems arise?

Why Choose Third Party Controls?Independent of Kit and Reagent Lot Changes

Bio-Rad Controls have up to 3 years of shelf life

-Fewer lot crossovers to perform

Goal of Quality Control:Evaluate and minimize analytical error

Use a system approach

• Minimize error through following operating protocols

– Calibration, maintenance, etc.• Assess daily performance

– Internal statistical quality control• Validate accuracy and precision periodically

– EQA (proficiency testing)

QC Vs Calibrators & Standards

• Calibration is “setting” the analyzer to give correct results– Using calibrating materials, not QC materials

• QC is checking to see if the analyzer is producing correct results– Checking the instrument’s calibration and other analytical

processes

• Standards also cannot be used as QC material- Multi-analyte standards are not available

How does basic QC work?

• Run a control sample • Compare result with expected range of values derived

from previous testing• Check to see if the result is right

– yes -- system is working• report good patient results

– no -- system is not working• do not report any bad data

Quality control- Frequency

• Should be run periodically

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• The closeness of the agreement between the measured values and the “true value” of the constituent. The best estimate of accuracy can be measured in two ways:

1. Reference Method2. Peer Group Comparison

Accuracy

The degree of replication or reproducibility.

The best estimate of replication uses both S.D. and CV to describe Precision.

Precision

• Mean

• Standard Deviation (SD)

• Coefficient of Variation (CV)

• Coefficient Of Variation Ratio (CVR)

• The Standard Deviation Index (SDI)

QC Statistics

• Mean-- Arithmetic average of set of data points e.g.. Set LDH QC values of 121,115,118,119,120

• Sum of the set-- 603 and themean-603/5=120.6 IU/L

• At least 20 data points to be collected from 20 or more separate runs to establish target values for control materials

Mean

• This quantifies the degree of dispersion of STANDARD data points about the mean and is used to set limits upon which control result acceptability is determined

Standard deviation is valuable when comparing methods or evaluating new instruments.

• A method/instrument --low standard deviation--consistent results• A method/instrument -high standard deviation --less certainty of accuracy of

diagnosis and therefore less effectiveness of treatment

Standard DeviationStandard Deviation

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How many levels of controls should a Laboratory be running?

Single Level Only

Two Levels of Control

Three Levels of Control

l Better Informed Decisions

l Reduces Number of Repeats

WESTGARD RULES- WHY ?

Westgard Rules

Random Error Systematic Error

Troubleshooting and Westgard Rules

Problem identified by Westgard rule violated

Systematic Error (bias) 1 3s, 2 2s, 4 1s, 10xShifts, drifts, or trendsCalibration failure

ORRandom Error (imprecision) 1 3s, R4s

Poor reproducibility / Outliers

EQAS Programs available with Bio-Rad

1. Clinical Chemistry Monthly EQAS2. Clinical Chemistry Biweekly EQAS3. Immuno Assay Monthly EQAS4. Immuno Assay Biweekly EQAS5. Hemoglobin EQAS6. Hematology EQAS7. Urine Chemistry EQAS8. Therapeutic Drug Monitoring EQAS

Coming Soon…..1. Coagulation EQAS2. Infectious Serology EQAS

Why to use an EQA Program?

• Increase confidence in your testing system• Tool for testing accuracy

• May be required for accreditation

• External, unbiased assessment

• Additional tool for trouble shooting

Bio-Rad EQAS Programs

• Set of 12 unknown samples• Assayed at regular intervals ( 1 vial every month OR

once in 2 weeks)• Results are sent to Bio-Rad every month • Results are compared to your peer group• Results are compared to your previous performance• Monthly reports are given to the labs

Your EQAS ReportsEssential Information for Busy Laboratory Managers

Your EQAS Reports

Bi-Weekly/Monthly Report

Provides informationfor each sample

in a cycle

End of CycleReport

Provides a summaryof laboratory performance

for the entire cycle

Cover Page (Lab No. and contact information)Summary of Your ResultsData Analysis by Individual Analyte (also referred to as the “Histogram Page”)Summary of Data on File

Bi-Weekly/Monthly Report

How your results compare to your Comparator ValueYour Results, and Units listed for each Analyte

“Summary of Your Results”Lists a summary of information for all analytes for this sample

Your Method Codes, Description and any Conversion Factors to be applied

Levels of Comparison for Statistics

METHOD (Instrument)e.g.Glucose Oxidase on Hitachi 911

Method GROUPe.g. All Glucose Oxidase assays

ALL RESULTS or MODEe.g. All Glucose methods

Example for Glucose:

If insufficient data for comparison

If insufficient data for comparison

All Results / Mode

Mode 1

Mode 2

Mode 3

Example of Multi-Modal Data Distribution:

Your Result

“Histogram Page”Provides statistics and easy-to-read graphs for each analyte

Your MethodYour GroupAll Results

Analyte Statistics provide theMean and SD for Your Method,

Your Group and All Results

Deviation from All ResultsDeviation from Your GroupDeviation from Your Method

… and your deviation from Your Method mean, Your Group mean and the All Results mean

Clinical assessment

… and as assigned by other labs (Your Method, Your Group and All Results)

Your Lab:

Histogram

Your Result

Different shading is used to identify Your Method, Your Group and All Results

Levey-Jennings Chartdisplays last 12 data points

The shaded boxes indicate the comparator used for plotting the Levey-Jennings and calculating

your Accuracy Score

Different symbols are used to indicate a change in comparator or late data

Your method information listed for each analyteYour Results submitted so far this cycle, listed for each analyte

“Summary of Data on File”Lists a summary of all information so far this cycle

Developing a QC ProgramFAQ’s

My control values are not on/Close to the mean as provided in the package insert range. What should I do?

- Establish your mean and ranges- Obtain peer information


My control values do not fall within your package insert range. What should I do?

- CALL The Manufacturer: Instrument or QC- Obtain peer information- Any changes to reagents / software?- Confirm change affects patients / QC?

How do I establish a range to use?

Brand New ControlNCCLS - At least 20 points from separate

runs - Standard recommendation NCCLS - May use fewer runs (provisional)

but replace with data from all 20 runs


How do I establish a range to use?

New lot of same control typeNCCLS - At least 20 points from separate

runs - Standard recommendation NCCLS - Perform parallel testing with old

lot over 20 runs prior to beginning new lot


My IQC data is good however EQA/ PT shows poor accuracy scores?

Daily QC- Indicator of precisionEQA / PT – True Indicator of Accuracy


Thank You

Bijesh K V

09884813506

[email protected]

mailto:[email protected]

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Basics of QC