بسم الله الرحمن الرحيم. professor of clinical pathology (clinical chemistry)...

بسم الله بسم الله الرحمن الرحيم الرحمن الرحيم

Professor of Clinical Pathology (Clinical Chemistry)Professor of Clinical Pathology (Clinical Chemistry)Faculty of Medicine, Mansoura UniversityFaculty of Medicine, Mansoura University

The Laboratory test begins with a The Laboratory test begins with a physician deciding which test to physician deciding which test to

order and ends with that order and ends with that physician evaluating the test physician evaluating the test

result. A process of brain to brain result. A process of brain to brain transmission of medical in transmission of medical in

formation. formation.

Problems arise primarily from imperfect processes, not from

imperfect people.

The quality problems are primarily management problems because only

management has the power to change work process.

The total system for a health care organization involves the

interaction of all of the following processes as well as

many others:

A.Patient examination.

B.Patient testing.

C.Patient diagnosis.

D.patient treatment.

Physicians might view a health care organization as a provider

of processes for:

Health care administrators might view the activities in terms of

processes for :

A.Admitting

B.Patient services

C.Discharging patients

D.Billing for costs of

service

Laboratory directors might understand their responsibilities

in terms of processes for:

A.Acquisition of

specimens

B.Processing of

specimens

C.Analysis of samples

D.Reporting of test

results

Laboratory analysts might view their work as processes for:

A.Acquiring samples

B.Analyzing samples

C.Performing quality control

D.Releasing patient test

results

Written Written order order

Specimen Specimen

Patient Patient preparation preparation

Specimen Specimen

preparationpreparation

MeasuremeMeasurement nt

CalculatioCalculatio

n n

ReporReport t

Test request

Interpretation

Quality Assurance (Q.A)Quality Assurance (Q.A)

The five Q framework

Defines how quality can be managed using the scientific method or the

PDCA cycle Plan do check Act:

• Quality planning • QLP

Includes analytical process and the general policies, practices and

procedures that define how all aspects of the work get done.

• Statistical.Statistical.• Non statistical: Non statistical:

e.g.: Linearity checks , reagent and standard checks and procedure.

• Q.A. quality assessment concerned with:Measures and monitors of laboratory

performance as:

• Q.I. quality improvement:

• Q.C.

Turaround Specimen identification

Patient identificationTest utility

Provides a structural problem-solving process

With better analytical quality a lab can eliminate repeat run requests for test (this

work is waste).

If quality are improved waste will be reduced which reduce cost and provide a

competitive advantage.

If quality means conformance to requirements, then quality costs must be

cost of conformance and cost of non-conformance.

To customer requirement

(To prevent problem)

For appraising performance

For poor analytical performance For analytical

quality

PREVENTION

I. Commitment.

II. Facilities and Resources.

III. Technical Competence.

IV. Technical Procedures.

V. Problem solving Mechanism.

Essential Elements for Q.A.

• Input from QC technologist or supervisors to initiate the mechanism.

• In service training program. • Specialized trouble shooting skills.

• Quality team responsible for problem solving (small groups).

Essential elements for Q.A.

Technical Technical procedures procedures

Technical procedures

Methodology

Standardization and calibration:

Reference calibrator material (RCM) (primary calibrator): by

definitive method (absolute physical quantity such as mass)

e.g. isotope dilution mass spectroscopy.

Test calibrator material (TCM) (secondary calibrator): by

reference method and high quality staff.


Structure of an accuracy-based measurement system showing relationships among reference methods and

materials .

Documentation of analytical protocols and procedures.

Monitoring of critical

equipment and materials.


The Monitoring of analytical quality by the use of:

• Levey – Jennings chart

• Westgard multirules • Cum Sum


Q.C.

P.T.

SD, bias and 6 sigma

Q.C.

Levey Jennings control chart:

Analyze control 20 different days mean ± SD.

Construct Control chart. Control limits set as the mean ± 3s.

Concentration is plotted on the y-axis versus time (run number) on the x- axis.

Introduce the control into each run & record the value.

Control limit:

± 2 SD when the number of

observation (n) is one false rejection problem (Pfr).

± 3 SD when n = 2 or more error detection (Ped is low).

Q.C.Levey Jennings chart

1 2 3 4 5 6 7 8 9 10

M-3SD

M-2SD

M-1SD

M

M+2SD

M+1SD

M+3SD

Run number

Con

cen

trati

on

s

Mean

Q.C.Q.C.Westgard Multirules Chart

I2s one excced mean ± 2SD ( warning that initiate

testing of other control rules).

I3s one excced mean ± 3SD ( Random error )

2222ss 22 consecutiveconsecutive control excced mean ±± 2SD2SD

(systemic (systemic error)error)

R4s 2 consecutive excced mean plus and minus

2SD)

( Random error)

41s 4 consecutive excced mean ± 1SD ( syst. syst.

errorserrors )

10x` consecutive deviation Less than 1SD on one

side (system errorssystem errors)

If the control is within mean ± 2SD in control:

Q.CQ.CWestgard chartWestgard chart

1 2 3 4 5 6 7 8 9 10

M-3SD

M-2SD

M-1SD

M

M+2SD

M+1SD

M+3SD

Run number

Con

cen

trati

on

s

Mean

12s (warning )

13s (random)

22s systemic

41s systemic

4s (Random)

Westgard Multirule Chart

PPfrfr is kept low is kept low

PPeded is improved is improved

A word fromDr. Westgard

Introduce two control specimens into each analytical run :

When both fall with 2s limits accept the analytical run and report the patient results. When one exceeds 2s limit hold the patients results and inspect the control data using l3s,

R45, 22s and 10x-

When one of these rules is out of control, reject the analytical run & don’t report the analytical

results .When all of these rules indicate that the run is

in control , accept the analytical run and report the patient results


R4s is applied only within a run –between Run interpritted as RE

Rule may be applied "across" materials one observations can be on the low,

concentration and the other on the high concentration as long as they are within

the same run .

Rules 22s, 41s and 10x rules can be applied across runs and materials.


This effectively increases n and improve the Ped of the procedure

Systemic error: Systemic error: caused by variations in:

Appear despite, Tightly Controlled, Analytical method

Instruments Technique

Reagents or other material

Q.C.

Random error:

Sample pipttingDissolving reagent

Mixing sample and reagents Baths temp instability.

The overall objective of these rules is to obtain a high probability of

error detection and a low frequency of false rejection of runs:

If the rules are violated it must:

Q.C.

Different QC procedures have different sensitivities or

capabilities for detecting analytical errors.

The best is that with lowest Pfr and highest Ped.

QC performance characteristics

Cumulative sum CUSUM chart

Calculate difference between mean & the result (e.g. mean 100 , result 110

the diff = 10) -add this difference to the following each day.

Interpret the chart data . Steep slope of the Cusum Line, suggest

systemic errorssystemic errors and the run is out of control.

QC

QCCUSUM

The Same as before but the difference is calculated between the estimated control

value and k1 or ku (mean ±SD):

The cusum calculation do not start until a control value exceeds a certain threshold above

(Ku) or below (K1) of the expected mean (X).

QCCUSUM

This difference summated for 2 weeks

If the summation exceed the control Limit the method out of

control

If the sign changed (+ - or the reverse the calculation

stopped the method is in – control

changed to

QCCUSUM

Calculations and Tabular Record for Decision Limit Cusum For Control

Material.

With X=100, S=5.0, kU = 105 , K1 =95,hu=13.5,h1=13,5).

QCCUSUM

Clinical correlation:

Q.C using patients data (Its efficiency is relatively low)

Correlation with other laboratory tests e.g. T4 and TSH, urea and

creatinine.

•Correlate clinical diagnosis with laboratory test results e.g. impossible

test result such as normal serum bilirubin in a highly jaundiced patients.

Inter laboratory duplicate:

•Divide sample into 2 aliquots and do analysis.

This is a simple Q.C. procedure used in absence of stable control

material.

Q.C using patients dataQ.C using patients data

Delta checks with previous test: •To detect certain errors e.g.

identification or labelling.

•Compare laboratory test results with value obtained on previous

specimens from the same patients.


Delta check limit based on 3-day interval in term % of change from the

initial value e.g. Na+ 5%, CK 99%.

Limit checks: •Patients test results should be reviewed to check that they are within the physiological ranges

compatible with life.

Low Low warning warning

High High warning warning

S. Albumin (g/dl)S. Albumin (g/dl) 1.51.5 6.06.0

S. Uric acid S. Uric acid (mg/dl)(mg/dl)

1.01.0 12.012.0

S. Sodium S. Sodium (mmol/L)(mmol/L)

120.0120.0 150150


External Q.C.External Q.C.

N. ± 1-1.5.> 2 Indicate that the Lab is not in agreement with the test of other

Laboratories in the program.Must correct any test method instrum.

trouble shooting.

Analyze the same Lot of control material:

SDI for the same instruments and techniques:

=


Comparison of Lab. Mean and group mean by t-test.

If significant (<0.05), the Lab. Result is biased.


Role of proficiency testing (PT) in AccreditationRole of proficiency testing (PT) in Accreditation

According to Clinical Laboratory Improvement Amendments (CLIA88)

Study 5 samples 3 times per year so as to improve the capability of detecting

"unacceptable“ performance.

The lab. must produce correct results on 4 out of 5 specimens for each of the

analytes in that category and have an overall score of at least 80% for 3

consecutive challenges.

The criteria of PT failure is:

Two of five incorrect results on two of three consecutive PT surveys

If there are 2 incorrect results for any analyte , The Lab. is considered "on

probation " Lab .

Suspended Lab:

If the lab .has 2 or more incorrect results for any analyte or has any score less than 80%

on two of three consecutive surveys.

Suspended Lab. must cease all analytes in that specialty category until it is

reinstated .

Target value (% or absolute value):

The mean of all responses after removal of outliers (more than 3SD).

Or the mean established by definitive or reference method (acceptable by the

national committee of standard NCS).

Comparative method may be used in absence of the former methods.

Post Analytical Goals and Post Analytical Goals and Clinical Interpretation of Lab. Clinical Interpretation of Lab.

ProceduresProcedures

The following questions must be asked for test results:

Screening : Is an apparent disease present ? Pathoghysiology : What is the disease

process ? Confirmation : How can Confidence in the

tentative diagnosis be increased ? Prognosis : How Severe is the disease

process ? Monitoring : Has a change occurred since the

Last observation ?

Is it significantly different from previous result ?

The probability that the difference between two result is analytically

significant (p< 0.05) is 2.8 times the analytical SD (SDA of repeated

measurements of a single quality normal control serum).

To decide whether an analytical change is clinically significant, it is necessary to

consider the extent of natural biological variation (means of SDB for repeated

measure ments made at weekly intervals in healthy subjects over 10 weeks).

The effects of analytical and biological variation can be assessed by calculating

the overall standard deviation of the test by:

If the difference between two test results exceeds 2.8 times the SD of the test, it can be considered of potential clinical

significant:

Is it consistent with clinical findings ?Is it consistent with clinical findings ?

LAB. TESTING PROCESSES AND LAB. TESTING PROCESSES AND

THEIR POTENTIAL ERRORSTHEIR POTENTIAL ERRORS

LAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORSLAB. TESTING PROCESSES AND THEIR POTENTIAL ERRORS

Process Potential Errors

Test

orderin

g

•Inappropriate test

•Handwriting not legible

•Wrong patient identification

•Special requirements not

specified

•Cost or delayed order



Specimen acquisition

•Incorrect tube or container

•Incorrect patient

identification

•Inadequate volume

•Invalid specimen (e.g.

hemolyzed or too dilute)

•Collected at wrong time

•Improper transport

conditions



Analytical measurement

•Instrument not •calibarted correctly •Specimen mix –up •Incorrect volume of specimen •Interfering substance present •Instrument precision problem



Test reporting

•Wrong patient identification •Report not posted in chart •Report not legible •Report delayed •Transcription error



Test interpretatio

n

•Interfering substances not recognized •Specificity of test not understood •Precision limitations not recognized •Analytical sensitivity not appropriate •Previous values not available for comparison

Six SigmaSix Sigma

Today’s competitive environment leaves no room for error

This is why six sigma quality must be a a part of our culture.

Six SigmaSix Sigma

What is six sigma

It is a process that helps us focus on developing and delivering near

perfect products and services.

Why sigma

The word is a statistical term that measures how far a given process

deviates from perfection.

The central idea behind six sigma is that you can measure how many” Defects” you have in a process, you

can systematically figure out how to eliminate them and get as close to

“zero defects” as Possible.

Six SigmaSix Sigma

The principles of Six Sigma go back to Motorola’s approach to TQM in the early 1990s and the

performance goal that “6 sigmas or 6 standard deviations

of process variation should fit within the tolerance limits of

the process”; hence, the name Six Sigma.

Six SigmaSix Sigma

Six SigmaSix Sigma

Six SigmaSix Sigma

Methods of sigmametric measurement

Sigma = (Tea – bias)/cv

Tea = tolerable error or allowable total error (determined by CLIA)

Bias = inaccuracy

Six SigmaSix Sigma

•3.4 DPM for a six-sigma process;

•233 DPM for a five-sigma process;

•6210 DPM for a four-sigma process;

•66,807 DPM for three-sigma; and

•308,537 DPM for a two-sigma process

A shift or bias of 1.5 sigma would hardly cause any defects in a six sigma process. The actual rates

that are expected are as follows:

Six SigmaSix Sigma

Six SigmaSix Sigma

Methods with 6 sigma performance are considered

“World class”.Methods with sigma performance less than 3 are not acceptable for

production.

Six SigmaSix Sigma

ChemistryTest or Analyte

CLIA Acceptable

Performance

Five-SigmaPrecision

Six-SigmaPrecision

Blood gas pCO2 5 mm Hgor 8% (greater)

1 mm Hgor 1.6%

0.8 mm Hgor 1.3%

Blood gas pH 0.04 pH units 0.008 pH units

0.00067 pH units

Calcium, total 1.0 mg/dL 0.2 mg/dL 0.17 mg/dL

Chloride 5% 1.0% 0.83%

Cholesterol, total 10% 2.0% 1.7%

Cholesterol, HDL 30% 6.0% 5.0%

Creatine kinase 30% 6.0% 5.0%

Creatinine 0.3 mg/dlor 15%

(greater)

0.06 mg/dLor 3.0%

0.05 mg/dLor 2.5%

Six SigmaSix Sigma

ChemistryTest or Analyte

CLIA Acceptable

Performance

Five-SigmaPrecision

Six-SigmaPrecision

ALT 20% 4.0% 3.3%

Albumin 10% 2.0% 1.7%

Alkaline Phosphatase

30% 6.0% 5.0%

Amylase 30% 6.0% 5.0%

Bilirubin, total 0.4 mg/dLor 20%

(greater)

0.08 mg/dLor 4%

0.067 mg/dLor 3.3%

Six SigmaSix Sigma

Glucose6 mg/dL

or 10% (greater)1.2 mg/dLor 2.0%

1.0 mg/dLor 1.7%

Iron, total 20% 4.0% 3.3%

LDH 20% 4.0% 3.3%

Magnesium 25% 5.0% 4.2%

Potassium 0.5 mmol/L 0.1 mmol/L 0.08 mmol/L

Sodium 4 mmol/L 0.8 mmol/L 0.67 mmol/L

Total protein 10% 2.0% 1.7%

Urea Nitrogen2 mg/dL

or 9% (greater)0.4 mg/dLor 1.8%

0.33 mg/dLor 1.5%

Uric acid 17% 3.4% 2.8%

Six SigmaSix Sigma

Toxicology Test or Analyte

Alcohol, blood 25% 5.0% 4.2%

Blood lead10% or

4 mcg/dL (greater)2.0% or

0.8 mcg/dL1.7% or

0.67 mcg/dL

Carbamazepine 25% 5.0% 4.2%

Digoxin20% or

0.2 ng/mL (greater)4.0% or

0.04 ng/mL3.3% or

0.033 ng/mL

Ethosuximide 20% 4.0% 3.3%

Gentamicin 20% 4.0% 3.3%

Lithium0.3 mmol/L or20% (greater)

0.06 mmol/L or4.0%

0.05 mmol/L or3.3%

Phenobarbital 20% 4.0% 3.3%

Phenytoin 25% 5.0% 4.2%

Primidone 25% 5.0% 4.2%

Procainamide 25% 5.0% 4.2%

Quinidine 25% 5.0% 4.2%

Theophylline 25% 5.0% 4.2%

Tobramycin 25% 5.0% 4.2%

Valproic acid 25% 5.0% 4.2%

Hematology Test or Analyte

Erythrocyte count 6% 1.2% 1.0%

Hematocrit 6% 1.2% 1.0%

Hemoglobin 7% 1.4% 1.2%

Leukocyte count 15% 3.0% 2.5%

Platelet count 25% 5.0% 4.2%

Fibrinogen 25% 5.0% 4.2%

Partial thromboplastin time 15% 3.0% 2.5%

Prothrombin time 15% 3.0% 2.5%

Six SigmaSix Sigma

بسم الله الرحمن الرحيم. professor of clinical pathology (clinical chemistry)...

Documents

process slide

methodology slide

sigma slide

s random slide

technical procedures

costs of service slide

sd warning

mansoura university