EQA and IQC

Question 1

Why is quality important?

Answer 1

• Best patient outcome
• Best patient experience
• Safe practice
• Need confidence in results produced

Question 2

What is Internal Quality Control?

Answer 2

Used in real time to monitor the performance of an assay.

• IQC is on the day so to check if we have the same result with different samples
• IQC – if we put this same sample through repeatedly would we get the same answer and is it close to the expected value?
• Checks reproducibility and accuracy of results ght material – is an assay producing the correct results for a patient sample?

Question 3

What is External Quality Assurance?

Answer 3

Retrospective analysis of performance of an assay in comparison to other users

• Do you produce the same results for the same sample as other labs with the same analyer?
• Do different platforms perform the same?

Question 4

What is the impact of IQC and EQA?

Answer 4

• Ensure patient analysed in the same lab will receive continuity of results and therefore clinical care
• Patients analysed in different labs should have equivalent results

Question 5

What is IQC/EQA material?

Answer 5

IQC

• Generally bought commercially
• Can contain one or multiple analytes
• Analytical results monitored by using a computer programme

EQA

• Obtained by signing up to an EQA scheme
• All assays should be subject to EQA
• If not sample exchange scheme

Question 6

What are the factors considered when choosing IQC material?

Answer 6

Matrix

• Close matrix match
• Human preferable, but not always possible

Third party

• At least one QC used should not be made by the assay manufacturer

Cost

• Most cost effective without compromising on quality

Levels available

• Minimum of 2 – normal (physiological) and high (pathological)
• Near cut off value

Range of analytes

• Able to QC multiple assays The different QCs you select need to cover your whole assay range

Stability

• Use repeatedly

Question 7

How often do you need IQC?

Answer 7

Depends on frequency of analysis

• Batch analysis requires IQC at least at the beginning and end. If large number of samples also benefit from IQC in the middle of a batch as well
• Continuous flow analysis requires IQC throughout the day. Depends on local policy and with new calibration/reagent lot

You can only guarantee the accuracy of results between acceptable IQC results

Also depends on the analyte

• Chemistry/Immunoassay
• Stability of calibration
• Reagent lot changes

Operator change (manual assays)

Question 8

What is target value in IQC?

Answer 8

• Precise assays will give different results upon repeat analysis of the same sample
• Target value is usually defined as the mean +/- 2 standard deviations
• Standard deviations will vary greatly between different assays

Question 9

How is the target value determined?

Answer 9

• Need to run up IQC
• Assayed IQC material is provided with target values
• Range of values tends to be huge!
• Assay should be able to perform in a much more reproducible form within controlled conditions of your laboratory
• New IQC material requires mean to be determined. Usually suggest determining intermediate precision by analysing IQC material 20 times on different days
• Standard deviation should be checked but should not change between IQC lots

Question 10

How is the IQC then assessed?

Answer 10

• IQC values within +/-2SD of the mean and report patient results
• If IQC is > +/-2SD but < +/-3SD, Warning sign – assess the situation (don’t necessarily need to reject the result but assess the assay)
• If IQC is >+/- 3SD, reject the run

Practice varies between labs

Question 11

What is systemic error and Random errors?

Answer 11

Systematic errors

• Proportional/Constant Bias
• Affects accuracy and see a distinctive bias

Random Errors

• Random deviation from the lab mean
• Affects precision/reproducibility

Question 12

What are causes of systematic errors?

Answer 12

• Incorrectly assigned calibrator
• Calibration lot changes
• Reagent lot changes
• Light source deterioration
• Reagent/calibrator deterioration

Question 13

What are causes of Random Errors?

Answer 13

• Inaccurate pipetting
• Analyser mis-sampling
• Sample contamination

Question 14

What are types of of random and systematic errors

Answer 14

Systematic

• Proportional
• Constant
• Mixed

Random

• Was there a mistake, inaccurate pipetting?
• Mis-sampling? – repeat! Be aware, repeated random errors may indicate a problem.

Question 15

What is Proportional Bias in Systematic Errors?

Answer 15

• A minimum of 2 points are needed - a calibrator and a blank
• Is your calibrator value correctly assigned?
• Is the calibrator expired / has it gone off?
• Has the calibrator been correctly stored?
• Has the calibrator lot changed without you realising?

Question 16

How is constant bias investigated?

Answer 16

• Is the assay / analyser working OK – the lamps? the cuvettes The reagents?
• Is there some positive or negative interference?
• Is there some contamination?
• Are the wash steps working correctly?
• Do you need more wash steps?

Question 17

What are some forms of EQA?

Answer 17

• NEQAS
• WEQAS
• IMMQAS
• RIQAS

Question 18

How is EQA undertaken?

Answer 18

• Receive a set of samples (normally 3 or 4 depending on the scheme). Don’t know the values
• Processed as normal samples, in order to assess the entire testing process
• Results reported to the EQA scheme
• The EQA scheme produces a report
• You keep a record of all your results in a managed system
• If you do not meet the performance criteria determined by the EQA scheme, the scheme will warn you, with a letter of poor performance.
• The schemes have put in place poor performance criteria which expect a 100% return rate.
• Return rate fail, or non-response to formal SO contact are becoming an automatic panel referral
• EQA = a constant analytical audit

Question 19

What are the purposes of an EQA?

Answer 19

• Assessment of inter-lab performance: Is a method consistent between labs?
• Performance between methods: Do different methods perform differently? Possible clinical implications
• Used in the laboratory quality system:an EQA KPI: the number of poor performance letters received
• Assessment of trends: e.g rising, falling, repeating pattern, constant positive or negative bias

Question 20

What the steps taken when poor performance isn’t acted upon?

Answer 20

• Local
• Scheme organiser
• Panel
• Joint working group
• UKAS
• CQC

Question 21

What are other considerations for EQA use?

Answer 21

• It can be used in method evaluation, to determine accuracy
• Poor EQA performance across labs using the same method can provide evidence to prompt a company to improve their method
• When you are looking to purchase a new piece of kit or method, you can check its EQA performance
• Network reports

Question 22

What are question to ask with poor EQA return?

Answer 22

• What’s the problem? High A score / B score / C score A bias Is it an isolated incident (random error)
• Is there a pattern? Was there a sudden shift? Is there a trend? What does the bias look like? Proportional (systematic error), Constant (systematic error)

Question 23

How is poor EQA return fixed?

Answer 23

A random error? Check the IQC

• Single random error, was the QC all OK?
• What does the precision of the assay look like?
• If this one sample has had a random error, could this be happening at other times?

A poor A/B score? Check the IQC

• If you have a continuous bias, you are not performing acceptably
• This should show up in your IQC
• If not, target and SDs of your IQC should be re-evaluated – the current settings are not picking up issues as they should
• A poor C score? This reflects the consistency of your bias. Are you always positive / negative, is it always to the same degree? A high C score indicates that your bias has been variable over the last 12 runs.

Question 24

What are different types of bias giving a poor C score?

Answer 24

Concentration-dependent bias

• [low] = positive bias
• [mid] = no bias
• [high] = negative bias

A change or shift in bias

• New calibrator
• Maintenance
• Lot change – cal / reagent

Analytical Imprecision

Question 25

What are disadvantages of EQA?

Answer 25

• Only indicates a snap shot in time, difficult to reflect laboratory over all performance.
• If you are compared against an ALTM and you aren’t the main method it’s difficult to know how well you’re performing
• When the group is too small – statistical comparison is difficult

Question 26

What is MAPS?

Answer 26

Minimal Acceptable Performance Standards

• The aim is to develop a single scoring system with specific standard for each analyte
• Started with these 5 analytes
• Derived from intra- and inter-individual biologic variation data

Question 27

What are current issues with MAPS?

Answer 27

• Different schemes – 34!
• Different scoring systems – 8!
• Different scoring criteria
• Different report formats
• Different schemes can be more or less ‘difficult’
• Evidence-based medicine can only be practiced if results are commutable between labs

Question 28

What are advantages and disadvantages of using multi rule IQC?

Answer 28

Advantages

• You miss fewer errors
• You get a clue to the problem
• You waste less time and you catch issues quicker – they can then often be resolved more quickly. This can improve turn around times.
• You save money by highlighting issues more quickly

Disadvantages

• The recommended rules vary depending on how many QC levels you use and the analyte
• You need specialist QC software
• Might you highlight too many issues