internal quality control (qc) for medical laboratories: an introduction dr. otto panagiotakis and...

Internal Quality Control (QC) for

Medical Laboratories: An introduction

Dr. Otto Panagiotakis and Dr. Alexander

Haliassos

ESEAP – Greek Proficiency Testing Scheme

for Clinical Laboratories

http://www.eseap.gr info@eseap.gr

• Analytical Quality Control •

The most important tool for ensuring the

quality of laboratory results through the

identification and reduction of errors

It includes two parallel mechanisms:

• Internal (intra-laboratory) quality control

• External quality control, or External quality

assessment (EQA) or Proficiency Testing (PT)

Correct result: There is not

a value, but a range from

repeated measurements

We need a tool to compare

the reported with the

expected result.

What means a value of total cholesterol

245mg/dL reported for the analysis of an QC

control?

235 245 255240 250 260

265

It is the control chart Levey-Jennings

Central horizontal line: expected mean value

Dotted horizontal lines: control limits (mean

± nSD)

Control charts Levey-Jennings:

+2s

mean

+1s

-1s

-2s

+3s

-3s

Their design is based on the assumption that:

• The values resulting from previous

measurements are subject to random variation

• This variation follows a uniform (normal)

distribution

Control charts Levey-Jennings:

How we draw the control charts?

• We select a parameter (p.ex. Cholesterol)

• we measure this parameter in a control

material for 20 days using the method (assay)

and the instrument (analyzer) that we evaluate

• from those values we calculate the mean and

the SD

p.ex. mean = 200 mg/dL and SD = 4 mg/dL

• subsequently, the control limits at the level of

2s, 3s

mean ± 2s: 200 ± 2(4)=200 ± 8 from 192 to

208

mean ± 3s: 200 ± 3(4)=200 ± 12 from 188 to

212

Cholesterol (mg/dL), Lot No: xxx, January 2015216

212

208

200

192

188

1841 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

x-3s

x+3s

x-2s

x+2s

mean

Interpretation of control charts (1)

• The control charts reflect the distribution resulting

from the initial measurements of the control

materials

• In the charts we draw the values of each

measurement

• Evaluation: depending on their position in the chart

1) If the analytical procedure is correct, the new

measurements will have the same distribution with the

originals:

• Extremely rare (0,3%) a value> mean ± 3s

• Unlikely (5%) a value> mean ± 2s

• Very likely (32%) a value> mean ± 1s (limits without a

value)

Control Rules

Rules to decide whether a series of

measurments is under control or out of control

Control rules control limits

12s mean ± 2s

13s mean ± 3s

Single rule methods

Multiple rules methods

2) If the analytical procedure has a problem, it

increases the probability of a value exceeding the

control limits

This can happen :

• Either with the appearance of a constant error

(bias) (shifting of the mean of the distribution to or values)

• or by increasing the random error

(enlargement of the distribution)

Situation out of control / Unacceptable results

Interpretation of control charts (2)

•

Situation under control (normal)

Systematic error (bias)

Distribution enlargement

The QC methods are detection systems

The detection systems have some characteristics:

The frequency of true warnings, true alarms

The frequency of erroneous warnings, false alarms

In the QC methods they are called respectively :

• Error detection probability (Ρ)

• Probability of false rejection (Ρο)

The ideal on a single rule QC method would be:

Ρ=1,0 (100%) and Ρο=0 (0%)

However, for each control rule: Ρ < 1 and Ρο > 0

A realistic goal is : Ρ=0,90 and Ρο=0,05

The problem of erroneous rejects

Rule 12s: high Ρ and high Ρο

For Ν=1 Ρο=5%

For Ν=2 Ρο=9%

For Ν=3 Ρο=14%

• The single rule QC method using the 12s rule

should only be used with Ν=1.

• If Ν=2, almost a false rejection in 10

• This is not a problem of the analytical

procedure.

• This is an intrinsic problem of the QC method

and related to the selected control threshold.

resulting in non detected large errors

As the control limits are extended erroneous

rejections (Po) decrease, but also P decreases

If a rule with high P is selected will have also

high Ρο

Single rule QC methods have serious drawbacks

Need to find other QC methods

Rule 13s: low Ρο and low Ρ

Multiple rules methods

They do not use a single control rule

but a combination of rules (at least 2)

Advantage: Low Po and simultaneously high P

The most well known Westgard method:

• 6 control rules

• 2 control sera (N=2) resulting to

• 2 Levey-Jennings control charts L-J, one

for each serum (control material)

• Control limits at three levels(±1s, ±2s,

±3s)

216

212

208

200

192

188

1841 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

x-3s

x+3s

x-2s

x+2s

x+1s

x-1s

204

196

Cholesterol (mg/dL), Lot No: xxx, January 2015

The 6 control rules according to Westgard

12S

13S

22S

R4S

41S

10x

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

Not a rejection but warning for a potential

problem Further control is required based on the

other criteria

Rule 12S

One value (measurement) > 2s limit

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

Applied in a series for each of the two sera

Sensitive to random errors

Rule 13S

One value (measurement) > 3s limit

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

Rule 22S2 consequent values > the same limit of 2s

In the last 2 series for each

serum

In the same series for both

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

1 2 3 4 5 6 7 8 9 10

1 2 3 4 5 6 7 8 9 10

In the last 2 series for each

serum

In the same series for both

Sensitive to systematic errors

Rule 22S2 consequent values > the same limit of 2s

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

In the last 2 series for each

serum

In the same series for both

Rule R4S

The difference in value of the two sera> 4s

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

1 2 3 4 5 6 7 8 9 10

1 2 3 4 5 6 7 8 9 10

In the last 2 series for each

serum

In the same series for both

Sensitive to systematic error

Rule R4S

The difference in value of the two sera> 4s

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

In the last 4 series for each

serum

In the last 2 series for both

Rule 41S

4 consecutive values > the same limit of 1s

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

1 2 3 4 5 6 7 8 9 10

1 2 3 4 5 6 7 8 9 10

In the last 4 series for each

serum

In the last 2 series for both

Sensitive to systematic errors

Rule 41S

4 consecutive values > the same limit of 1s

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

In the last 10 series for each

serum

In the last 5 series for both

Rule 10Χ

10 consecutive values at the same side of the mean

1 2 3 4 5 6 7 8 9 10

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

+3s +2s +1smean - 1s - 2s - 3s

1 2 3 4 5 6 7 8 9 10

1 2 3 4 5 6 7 8 9 10

In the last 10 series for each

serum

In the last 5 series for both

Sensitive to systematic errors

Rule 10Χ

10 consecutive values at the same side of the mean

values

12s

Situation out of control - Series Rejected

Situation under control - Series Accepted

Flowchart according to Westgard

13s 22s R4s 41s 10x

yes

yes yesyesyesyes

no no

no

no

nono

control

Differences of Internal and External QC

Internal QC

• performed daily in the laboratory

• uses samples (control materials) of known concentration

• it is always required

External QC

• performed periodically (weekly, monthly …)

• uses samples (control materials) of unknown concentration

• useful in conjunction with the internal QC

External QC does not replace the Internal

QC

• the inter-laboratory comparisons are infrequent

• the results are reported deferred (not in real

time) and therefore it is not possible the

immediate intervention with corrective measures

• even if the performance is satisfactory, it

assures the proper functioning of the laboratory

only on the day of the inspection (participation)

These programs do not lead to quality

improvement of the laboratory if it is not

performed daily the internal QC.