Transcript PK & PK/PD MODELLING WORKSHOP National Veterinary School

Exercise 7:
Accuracy and precision
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Origin of the error :
Accuracy and precision
• Systematic (not random)
– bias
– impossible to be corrected
 accuracy
• Random
– can be evaluated by statistics
 precision
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Bias and precision
Gold
Standard
Silver
Standard
Off-Base
Model
Hit or
Miss Model
Good Precision Poor Precision Good Precision Poor Precision
Good Accuracy Good Accuracy Poor Accuracy Poor Accuracy
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Accuracy
Closeness of determined value to the true
value.
The acceptance criteria is mean value 
15% deviation from true value.
At LOQ, 20% deviation is acceptable.
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Accuracy
The accuracy is calculated using the following
equation :
Observed value  Theoritica l value
Accuracy (%) 
Theoritica l value
The accuracy at each concentration level must
be lower than 15% except a LOQ (20%)
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Precision
The closeness of replicate determinations of a
sample by an assay.
The acceptance criteria is  15% CV.
At LOQ, 20% deviation is acceptable.
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Precision
Repeatability (r)
Agreement between successive measurements
on the same sample under the same conditions
Reproducibility (R)
The closeness of agreement between results
obtained with the same method under different
conditions
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Precision… Considered at 3 Levels
• Repeatability
• Intermediate Precision
• Reproducibility
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Repeatability
• Express the precision under the same
operating conditions over a short interval of
time.
• Also referred to as Intra-assay precision
– (within day)
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Intermediate Precision
• Between-run, between day repeatability … also named
intermediate precision, which measures precision
with time (often days) and may involve different
analysts, equipment, reagents…
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Precision: measurement
• Should be measured using a minimum of
5 determinations per concentration
– A minimum of 3 concentrations in the range
of expected concentrations
– The precision at each concentration should
not exceed 15% except for the LOQ (20%)
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Raw data
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Precision: measurement
• for a single measurement : CV(%)
• for intra-day and inter-day precision
 ANOVA
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2
 between
Variance of intermediate precision

2
Total

2
between

2
within
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Estimation of the two components
of the variance
• we need a proper statistical model that is
the one-way nested analysis of variance
model given as :
Yij    bi  wij
With i=1,2..n days and j=1,2,…replicates;
in this equation, Yij are observed values, μ is the true value of the common stock solution
being assayed in this experiment, bi is a random component for between-days variation
and wij is another random component for within-day variation. The variance of bi is
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ANOVA
• Allows an estimation of the 2 variance terms
– inter-day mean square (BMS)
– intra-day mean square (WMS)
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The exercise consist to compute
these variances
• By hand
• Using an ANOVA (Excel)
• With Analyse- it
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The limit of quantification (LOQ)
• LOQ is the lowest amount of analytes
in a sample which can be determined
with defined precision and accuracy
• LOQ :  20%
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Limit of quantification (LOQ)
• The lowest standard on the calibration
curve is the LOQ if:
– no interference is present in the blanks at
retention time of the analyte for this
concentration
– the response (analyte peak) has a precision
of 20% and accuracy 80-120%
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Three analytical areas
LOD
1
LOQ
2
3
Xb
not detected
Area of
detection
Area of
quantification
or CV<20%
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