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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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