Basic knowledge of POCT instuments - mtcouncil.org Bangsan3.pdfBasic knowledge of POCT instuments...

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Basic knowledge of POCT instuments

The Tide Resort The Tide Resort BangsanBangsan Beach Beach 18 June 200918 June 2009

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POCT instruments concepts

•User friendly, Reducing dependence on operator technique.

•Potentially improve patient outcomes

•Example :Electrolyte, Hct, Blood gas and metabolites, Cardiac injury markers, Hemostatisindicator, Drugs of abuse, Infectious disease markers, Molecular diagnostics

• Point of care testing

• Diagnostic medical devices used at or near the site of patient care

•Bed site, OR, ED, ICU, field, home

•. Provide near real time analysis and rapid test results• Reduce therapeutic turnaround time

•Shorten length of hospital stay

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Classification

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ClassificationCharacteristic Transportable Portable Handheld Immuno

detection device

Size Large and heavy On carts for mobile use

Medium easier access to patients

Small or miniature

Medium to miniature

Power source AC, Batteries back up for short term use

AC or Batteries

Batteries Variable to none

Test menu Broad test menu, Customize the tests

Fixed, Single to multi test

Fixed / limited

Fixed, Single to multi test

Sampling method

Automatic for reducing dependence on operator technical /manualMinimize the volume of blood need per analysis.WB, P, S, U, CSF.

Automatic/manualW, P, S, U

ManualWB

ManualWB,P, U, Saliva

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ClassificationCharacteristic

Transportable Portable Handheld Immunodetection device

Instrument Blood gas system.

Blood gas, PT ,aPTT, HbA1c, Chemistry,

Blood gas, Glucose meter

Cardiac testing, Drug abuse, D-Dimer

Electrode/sensor,Reagent

The electrode/sensor, reagents, cartrige/cuvetteare separated and removable.

The electrode /sensors and reagents are built and packaged within the disposable cartridge.

The electrode and biosensor are constructed in to the test strips, Dry-reagent chemistryCalibration Automatic

internal one and two point calibration that is performed periodically

Periodic or prior to testing depend on multiple or single use cartridges

Don’t have internal calibration but have electronic verification steps

No calibration is needed

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ClassificationCharacteristic Transportable Portable Handheld Immuno

detection device

Biohazard Build in biohazard container

Build in biohazard container

Lack of waste storage, Exposed to biohazards

Biohazard storage

LIS connectivity

Available Possibly available

Limited none

Password security

Available Possibly available

Limited none

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Amperometer

CoaguChek XS

Principle

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Reflectance photometry

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Reflectance of u 411

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Digital camera chipReflectance of h232with CCD (Charge couple devices)

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QC•Conventional method

•Manual external introduction

•Automatic QC testing

• Omni system

•Automatic draw QC materials which are onboard at operator defined schedule

•Intelligent quality control ( iQC )

•Piccolo system (Abaxis) USA

•Verifies the chemistry, Optics and Electronics function of the analyzer during each run.

•No operator interaction

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QC

The integrated Quality Control (QC) function

•The fill detect system will indicate that an adequate sample has been applied to the test strip.

•Checks each test strip. Misuse, such as improperstorage of the test strip in hot and humid environment as well as exposure to extended ambient light, can be detected by the system. In the case of misused test strips a QC error will be displayed on the device.

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QCElectronic quality control

•Available portable and handheld instruments

•Supplements the traditional liquid QC procedures

•Evaluation of the optics, electronic and computational component of the system

•Does not validate the performance and functionality of the cartridge.

•Is not designed to replace liquid QC testing

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Potential sources of errors in POCT• Pre-analytic

•Patient identity

•Specimen collection

•Incorrect, mishandled, expired, unlabeled or unstable of test strips, cartridges, cassettes, or reagents

•Leukocytosis > 50,000 /ul, Thrombocytosis >600,000/ul, anemia (Hb < 7.5 g/dL), pH, Osmolarity, protein, lipid, heterophile Ab, Autoimmune

•Direct or indirect effects of transfused blood products or additives

• Analytic

•Physical (Temp, altitude, vibration, humidity)

•Sample (bubbles,viscosity, thrombi

•Calibration protocol not followed, calibration code wrong

•Sensor drift, aging

•Newborn glucose limits

•Lack of IQC, EQA, PT

•Operator not qualified, certified

•Maintenance

•Unstable power source

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Potential sources of errors in POCT• Post-analytic

•Critical values omitted, not recognized

•Wrong units,

•No results documentation

•No LIS

•No patient demographics

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Selection and Evaluation of POCT• System performance

•Broad test menu

•Accuracy, precision, resolution, reproducibility, stability, and response time

•Linearity

•Relationship to tests performed in the main lab

•Compatibility with other in vitro, ex vivo, in vivo

•Artifact elimination, error detection, interference warning and specimen flagging

• Technical and quality features

•Throughput, automated calibration, interrupt capability, duration of analysis cycle

•Compact, reliable, durable, light weight, mobile, and power efficient with battery operation

•Reagent stability, shelf life, lot size

•Continuous quality improvement (quality control, quality monitors, proficiency testing)

•Compliance with federal, state and accreditation regulation

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Selection and Evaluation of POCT• Conservation of patient blood volume

•Specimen volume type and matrix (eg.,whole blood, plasma, or serum) accepted

• Safety, ergonomics, security, and risk

•Biohazard control, containment, and disposal

•Speed, ease, simplicity and user friendly operation

• Economic efficacy

•Flexibility, Modularity, Exchangeability, expandability and upgrade capability

•Cost of instruments, consumables, and maintenance

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Selection and Evaluation of POCT

• Information interpretation and integration

•Remote review, remote control, and data management system

•Networking interfacing and wireless communications and critical results notification

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Top 5 requirements for POCT

•Connectivity including data management

•Low cost solutions

•Easy to use •Customer support•Accurate and precise results that correlate with the laboratory

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Method validation•Moderately complex test methodology

•Comparison of method (accuracy)

•Replication experiment (precision)

•Linearity experiment (reportable range)

•Verification of reference range

•Highly complex test methodology

•A waived or moderately complex test methodology, if modified by the user, automatically become high complexity

•Comparison of method (accuracy)

•Replication experiment (precision)

•Linearity experiment (reportable range)

•Detection limit experiment (Sensitivity)

•Interference experiment

•Recovery experiment

•Extensive reference range

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ImprecisionGlucose

No. L1 L2

1 99 282

2 99 277

3 99 281

4 98 280

5 99 278

6 99 278

7 98 278

8 99 283

9 99 278

10 96 279

11 97 276

12 95 281

13 96 275

14 99 276

15 98 278

16 98 280

17 98 284

18 97 281

19 98 281

20 98 283

MEAN 98.0 279.40

SD 1.19 2.01

%CV 1.22 0.72

•Criteria of acceptant

•Imprecision

•N ≥ 20

•Level ≥ 2

•Within run or between run ≤ 0.25*TE

•Between run ≤ 0.33*TE

•Example TE Glucose = 10%

•Criteria of within run ≤ 2.5%

•L1 = 1.22 PASS

•L2 = 0.72 PASS

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Comparison chart

No GLUCOSE (mg/dL)

RXL c501

1 82 90

2 76 86

3 87 98

4 79 84

5 87 96

6 264 283

7 50 53

8 200 219

9 86 92

10 102 107

11 84 91

12 113 118

13 93 100

14 105 113

15 118 126

Correlation( r ) 0.9991

Slope 1.0741

Y-Intercept 0.6396

T-TEST 0.6761

C501 & RXL

y = 1.0741x + 0.6396R2 = 0.9983

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100

150

200

250

300

50 100 150 200 250 300

RXL

c501

Minimum criteria

N = 20, 40

Duration = with 2 hrs / 5 days

r < 0.99

r2 < 0.95

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•Criteria of acceptant•Inaccuracy•SE + RE = % Bias + (3*% CV ) ≤ TE

•Bias = ( (xc * b) + a ) –xc = (100 * 1.0741) + 0.6396 = 108.04 - 100 = 8.04

•%Bias = Bias * 100 / xc = 8.04 *100/100 = 8.04

•%CV = 3*1.22 = 3.66

•%Bias + (3* % CV) = 8.04 + 3.66 = 11.7 FAIL

Parameter Within Run Precision

Acceptable%CV Comparison

a b Xc SE %bias%RE TEcal

%TEa

conc. %CV 1/4 of TEa between intercept slope Yc-Xc value Absolute (CV) %

98 1.22 2.5 0.6396 1.0741 120 9.5257 7.9 7.9 1.22 11.6 10

279 0.72 2.5 0.6396 1.0741 180 13.969 7.8 7.8 0.72 9.9 10

99 1.82 2.5 3.2898 0.9846 120 1.4406 1.2 1.2 1.82 6.7 10

241 0.68 2.5 3.2898 0.9846 180 0.516 0.3 0.3 0.68 2.3 10

C1 & C2

C1 &RXL

Glucose

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Precision chart

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Comparison chart

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The linearity or Reportable rangeExperiment

• Clinical and Laboratory Standards Institute (CLSI) recommends a minimum of at least 4 and preferably 5 different levels or concentration

Materials

standard solutions

linearity set from manufacturers

proficiency testing agencies

pools of patient specimen when high values are available

in some cases e.g.TDM spike a pool with the analyte to be measured

Selection of the diluent

• General chemistry tests; water and saline will be OK

• For other tests; better to use bovine or serum albumin preparations; specimen with low concentrations; drug free serum

• Follow the manufacturer’s recommendation of the diluent to use

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Linearity

• Procedure for preparation specimen

• 2 pools;• one near the zero level or close to detection limit.• The other near or slightly above the expected upper limit

of the working range

• Pool1 : low pool• Mixture2 : 3 parts pool1+1 part pool5• Mixture3 : 2 parts pool1+2 part pool5• Mixture4 : 1 part pool1+3 part pools5• Pool5 : high pool

Mix 1 Mix 2 Mix 3 Mix 4

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LinearityNumber of replicate measurements• NCCLS recommends 4 measurements on each specimens• 3 replicates are generally sufficient.

Pool or Mixture Mean (Y) Theoretical (X) % Recovery

Pool 1

Mean value Mean pool 1 Y1*100/X1

Mixture 2 Pool1 : Pool5 3 : 1

Mean value (Mean pool1 * 3) + (Mean pool5 * 1)/4 Y2*100/X2

Mixture 3 Pool1 : Pool5

2 : 2

Mean value (Mean pool1 * 2) + (Mean pool5 * 2)/4 Y3*100/X3

Mixture 4 Pool1 : Pool5

1 : 3

Mean value (Mean pool1 * 1) + (Mean pool5 * 3)/4 Y4*100/X4

Pool 5

Mean value Mean pool 5 Y5*100/X5

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LinearityTheoretical

valueMeasment

value% Recovery

Pool 1 0 0 #DIV/0!

Mixture 2 200 205 102.5

Mixture 3 400 418 104.5

Mixture 4 600 585 97.5

Pool 5 800 820 102.5

Linearity experiment

90.0

95.0

100.0

105.0

110.0

1 2 3 4Dilution

%R

ecov

ery

M ix 2 M ix 3 M ix 4 Pool 5

Linearity experiment

0

200

400

600

800

1000

0 200 400 600 800 1000

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Verify reference interval

Criteria

• Transference technique• Reference population N= 20

• Blood donor• Hospitalization• Alcohol consumption• Blood pressure abnormal• Drug abuse• Tobacco use• Pregnancy• Oral contraceptives etc,.

• 95% percentile acceptableN = 20 criteria acceptance ≤ 1 that out of reference range

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Sensitivity or Detection limit experiment

Analytical sensitivity (lower detection limit)

Immunology• The detection limit represents the lowest analyte level that can bedistinguished from zero. It is calculated as the value lying two standarddeviations above that of the lowest standard (master calibrator,(standard 1 + 2 SD, within-run precision, n = 21).

Chemistry• The lower detection limit represents the lowest measurable analytelevel that can be distinguished from zero. It is calculated as the valuelying three standard deviations above that of the lowest standard(standard 1 + 3 SD, within-run precision, n = 21).

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Sensitivity or Detection limit experiment

• The limit of blank (LoB).. The limit of blank corresponds to the concentration below which analyte freesamples are found with a probability of 95%.

LoB = mean blank + 1.65 SD blank

• The limit of detection (LoD). The limit of detection corresponds to the sample concentration which leads with

aprobability of 95% to a measurement result above the limit of blank.

LoD = LoB + 1.65 SD blank

• The limit of quantitation (LoQ) is the lowest concentration that canbe reproducibly measured with the between run coefficient of variation of < 20%.

LoQ = Bias spike + 2SD spike

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Criteria of acceptance

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Waived tests requirements by accrediting agency

Requirement CLIA JCAHO CAP

Daily QC requirement Follow test manufacturer’s direction

Follow test manufacturer’s direction

Doesn’t recognize waived testing. All tests must meet the same standardsParticipation in

regulatory proficiency testing

Only for CLSI regulated analytes

Only for CLSI regulated analytes

For all analytes when proficiency test is available

Establishment of accuracy (twice each year) for analytes not in proficiency testing

Yes Yes Yes

Method verification before implementation

No Accuracy, precision, reportable range, and appropriateness of reference ranges

Accuracy, precision, reportable range, sensitivity and appropriateness of reference ranges

Method verification before implementation for multiple instrument, same model

No No Yes

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Selected POCT requirementsRequirement CLIA JCAHO CAP

Assessment of accuracy at least every 6 months

No Yes Yes

Assessment of reportable range every 6 months

No No Yes

Method correlation at least every 6 months

For test results from different methodologies under the same CLIA certificate

For test results from different methodologies across entire JCAHO

For test resutls from different methodologies under the same CLIA certificate

Moderately complex testing QC for most analytes

2 levels of QC per day. More frequent evaluation is required for some analytes

2 levels of QC per day. More frequent evaluation is required for some analytes

2 levels of QC per day. More frequent evaluation is required for some analytes

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Selected POCT requirementsRequirement CLIA JCAHO CAP

Accepts electronic controls

Yes, follow manufacturer’s recommendation

Yes, with verification of manufacturer’s claims and periodic assessment with liquid controls

Yes, with verification of manufacturer’s claims and periodic assessment with liquid controls

CAP,College of American Pathologists, CLIA, Clinical Laboratory Improvement Amendments, JCAHO, Joint Commission on Accreditation of Healthcare Organizations.

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Selected POCT requirements Requirement CLIA JCAHO CAP

Non waived test Unmodified Moderate and high complexity

AccuracyPrecisionReportable rangeVerify reference range

AccuracyPrecisionReportable rangeVerify reference range

AccuracyPrecisionReportable range

Non waived test Modified or developed in house

AccuracyPrecisionReportable rangeVerify reference rangeAnalytical sensitivityAnalytical specificity (interfering substances)Recovery

AccuracyPrecisionReportable rangeVerify reference rangeAnalytical sensitivityAnalytical specificity(interfering substances)

AccuracyPrecisionReportable rangeAnalytical sensitivityAnalytical specificity(interfering substances

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