4 Quality Analytical Methods

Question 1

What are the 5 steps process to establish a new analytical method/ changes?

Answer 1

1. Selection
2. Evaluation
3. Implementation
4. Maintenance
5. QC

Question 2

In method selection/ design study, what are the 3 factors to consider? (MAP)

Answer 2

1. Methodology What analyte does the method test for?, How does the test compare to the current method?
2. Application What is the cost?, Will it meet lab TAT?
3. Performance How precise/ accurate will results be?, How sensitive is the method?

Question 3

In method evaluation/ method validation, what does the lab have to do when receiving a new instrument/ method from a manufacturer?

Answer 3

A lab must prove the method is acceptable for use by verifying that the method meets the manufacturer’s claims

Question 4

What is the purpose of method evaluation/ method validation?

Answer 4

To perform error assessment

Question 5

In method evaluation/ method validation, what do end users need to verify?

Answer 5

End users need to verify the criteria are being met for their specific patient population

Question 6

What is error assessment?

Answer 6

Error assessment is making sure that the errors are small enough so that not a big change will be made to the test result/ patient care

Question 7

To be eligible for medical decision making, what are the 2 criteria lab testing must meet?

Answer 7

Regulatory and scientific criteria

Question 8

Who sets target ranges for total allowable error (TEa) in clinical chemistry tests?

Answer 8

The Clinical Laboratory Improvement Amendments (CLIA)

Question 9

True or false - total allowable error (TEa) is always bigger than total error (TE)

Answer 9

True

Question 10

What are the 3 steps in evaluation? (FSVA)

Answer 10

1. Familiarization
2. Determining stability of calibrators, controls and reagents
3. Perform verification assessment validate/ proof manufacture’s method

Question 11

What happens in Implementation?

Answer 11

The procedure for the method is being written out, the method is put into routine use, QC procedure is put in place to monitor the method, sources of problems/ preventative maintenance procedures gets done

Question 12

Why is Maintenance of Equipment and Instrument / Quality Control necessary?

Answer 12

Periodic maintenance gets done on the instruments and Quality Control is necessary to ensure high quality test results

Question 13

Define the error and what it cause: Random error

Answer 13

Is unpredictable error (data points are up and down) and causes imprecision

Question 14

Define the error and what it cause: Systematic error

Answer 14

Shifts data/ data trends in one direction and causes inaccuracy

Question 15

Define the error and what it cause: Constant error

Answer 15

Systematic error will stay the same even if analyte concentration changes. It causes inaccuracy

Question 16

Define the error and what it cause: Proportional error

Answer 16

Systematic error changes as concentration of analyte changes. It causes inaccuracy

Question 17

How do we calculate Total Error?

Answer 17

TE = SE + RE

Question 18

Define allowable total error

Answer 18

Is error undetected during evaluation but the error has to be established before method evaluation

Question 19

In terms of error, when is method performance ok?

Answer 19

When total error is less than allowable total error

Question 20

In verification assessment, how do we check the reportable range of method?

Answer 20

By determining linearity. This is done by analyzing the analyte of interest in increasing concentration

Question 21

In verification assessment, what are the 3 ways to measure accuracy?

Answer 21

1. Method comparison - evaluate a new method against a reference method - difficult to do
2. Side by side comparison - run 40 specimen using both method and then compare the results with statistical calculations
3. Clinical correlation - *Test results should match patients’ diagnosis, clinical symptoms or other lab tests**

Question 22

In verification assessment, what are the 2 ways to check for precision?

Answer 22

1. Within run replication - *three samples are run at least 10 times in the same run and should give same results - intra-assay
2. Between run replication - at least three samples run at least 10 times on different days and should give same results - inter-assay

Question 23

In verification assessment, how do we check for analytical sensitivity?

Answer 23

Minimum limit detection - *use low level of analyte to determine the lowest measurable concentration

Question 24

In verification assessment, what are the 2 ways to check for analytic specificity?

Answer 24

1, Interfering substances
2. Cross-reactivity