Assessment of Analytical Performance

Question 1

Analytical performance vs diagnostic performance

Answer 1

Analytical- assess how well an instrument/method measures analyte of interest

Diagnostic- assess the ability of a test to discrimminate between a healthy and unhealthy patient (follows analytical)

Question 2

What can be investigated to assess the performance of analytical and diagnostic performance?

Answer 2

Precision
Accuracy
Specificity
Sensitivity

Question 3

Why is there a need to monitor analytical performance?

Answer 3

-Ensure reliability of data
-Quality control- stability of lab tests
-Meet requirements of regulatory bodies e.g CORU, INAB to ensure high standard of patient care
-Validation - assess performance characteristics
-Calibration - maintain accuracy
-Comparison

Question 4

How can precision be evaluated?

Answer 4

By performing
1) With-in-run precision study (intra-assay)
2) Between-run precision study (inter assay)
3) Precision profile

Can numerically define by SD and Coefficient of variation CV

Question 5

What is standard deviation?

Answer 5

-A quantity or numerical value that measures the deviation of data from the mean

Question 6

Low vs High SD values?

Answer 6

Low SD means data points are close to the mean/expected value
High SD means data points are spread out from the mean/expected value

Question 7

What is the significance of SD?

Answer 7

Depends on what is being assessed
-can assess analytical and diagnostic performance

Question 8

Look at formula for SD and be able to do on calculator

Question 9

Data with a normal distribution?

Answer 9

-68.3% of data is within 1SD from the mean
-95% of data is within 2SD from the mean
-99.7% of data is within 3 SD from the mean

Question 10

What is precision?

Answer 10

Relates to variation around a central value
e.g if 1SD then tightly together so v precise

Question 11

What are reference ranges usually?

Answer 11

The mean +/- 2SD

Question 12

What is CV?

Answer 12

Coefficient of variation - scales the SD by the size of the mean
%CV= SD/mean x 100
-makes it possible to compare across variables measured on different scales
-allows comparison of variability estimates regardless of magnitude of analyte conc

Question 13

What is in-run precision / intra assay?

Answer 13

-Only uses 1 analyst
-Closeness of agreement between results of successive measurements obtained under identical conditions
-e.g quality control samples representing low, medium, and high conc values are assayed in replicates of n=20 on same day

Question 14

What is between-run precision/inter assay?

Answer 14

-May be more than 1 analyst
-QC material representing low, medium and high conc values are assayed in replicates of around n=20 in different analytical runs over different days

Question 15

What is a precision profile?

Answer 15

-Examine the variation of a method over a number of analyte concentrations, days, and optionally over one or 2 runs per day
-A plot of %CV versus conc
-Can be used to establish working reference ranges
-Ensures that imprecision is below a pre-established level
-This level is largely dependent on clinical considerations

Question 16

What is the requirements of precision profile?

Answer 16

1. Atleast 3 replicates must be observed for each run and each run must have the same number of replicates
2. Analyte conc must be known

Question 17

What is accuracy and what is the formula for it?

Answer 17

-The nearness of a result to the true value

Inaccuracy = nominal value-experimental value
%Inaccuracy = nominal value - experimental value / nominal value x 100

Question 18

Relationship between accuracy and error?

Answer 18

High accuracy means low error

Question 19

Accuracy vs Precision?

Answer 19

-Accuracy indicates the proximity of measured results to the true value

-Precision indicates the repeatability or reproducibility of the measurement

look at diagram

Question 20

Look at recovery matrix slide

Question 21

What is specificity?

Answer 21

-Measures the proportion of negatives which are correctly identified (true negatives)
-The lower the specificity, the higher the chance of false positive
-Accuracy depends on specificity

Question 22

How to test specificity?

Answer 22

-Test that identifies the presence/absence of a specific genetic mutation
-Calculate the percentage of healthy people who are correctly identified as not having the mutation
-Specificity relates to the ability of the test to identify negative results
-Defined as proportion of patients who do not have the disease who will test negative for the mutation

Question 23

Specificity formula?

Answer 23

specificity = no. of true neg / no. of true neg + no. of false pos

Question 24

What is sensitivity?

Answer 24

-Relates to the ability to identify positive results correctly
-The higher the sensitivity, the lower the chnace of a false negative result

Question 25

What does complete sensitivity mean?

Answer 25

-A test is positive in every patient that has the disease

Question 26

What is limit of detection limit (LOD)?

Answer 26

The lowest quantity of a subsnatnce that can be distinguished from the absence of that substance with a degree of confidence -also refers to the range over which a quantitative assay can accurately measure the analyte

Question 27

Sensitivity formulaß

Answer 27

Sensitivity = no. of true pos / no- of true pos + no. of false neg

Question 28

Why is laboratory data compared?

Answer 28

1. Purchased a new analyser 2. Anew method introduced 3. A quicker, more convenient, or more economical adaptation to an existing method