L3 CLIN CHEM LEC - Methods of Evaluation and Quality Management

Clinical Chemistry

↳ Pre Analytic (Sample Processing)

.

↳ Analytic (Chemical Analysis)

.

↳ Post Analytic (Data Management)

Sample

Chemical

Data

CLINICAL CHEMISTRY:

.

↳ Pre Analytic (___________ Processing)

.

↳ Analytic (____________ Analysis)

.

↳ Post Analytic (_______ Management)

Method Evaluation

UNDER QUALITY MANAGEMENT:

.

↳ Used to verify the acceptability of new methods.

acceptability

METHOD EVALUATION:

.

↳ Used to verify the _______________ of new methods.

Quality Control

UNDER QUALITY MANAGEMENT:

.

↳ Insurance of a method to remain valid over time.

valid

QUALITY CONTROL:

.

↳ Insurance of a method to remain ________ over time.

Descriptive Statistics

↳ Used for monitoring test performance and QC.

performance

DESCRIPTIVE STATISTICS:

.

↳ Used for monitoring test ________________ and QC.

6 Sources of Analytic Variability

UNDER DESCRIPTIVE STATISTICS:

.

↳ Operator Technique

.

↳ Instrument Differences

.

↳ Test Accessories

.

↳ Contamination

.

↳ Environmental Conditions (Temperature, Humidity)

.

↳ Reagents

.

↳ Power Surges

.

↳ Matrix Effects (Hemolysis, Lipemia, Etc.)

Differences

Test

Humidity

Power

Matrix

SOURCES OF ANALYTIC VARIABILITY:

.

↳ Operator Technique

.

↳ Instrument ________________

.

↳ _______ Accessories

.

↳ Contamination

.

↳ Environmental Conditions (Temperature, _____________)

.

↳ Reagents

.

↳ _________ Surges

.

↳ ________ Effects (Hemolysis, Lipemia, Etc.)

Measures of Central Tendency

UNDER DESCRIPTIVE STATISTICS:

.

↳ Mean, median, mode.

Mean

UNDER MEASURES OF CENTRAL TENDENCY:

.

↳ Average score of a dataset.

Median

UNDER MEASURES OF CENTRAL TENDENCY:

.

↳ Middle value of the data set after the data have been ranked.

Mode

UNDER MEASURES OF CENTRAL TENDENCY:

.

↳ The most frequent occurring value in the dataset.

Measure of Spread

UNDER DESCRIPTIVE STATISTICS:

.

↳ Range, Standard Deviation (SD), Coefficient of Variation (CV).

Range

UNDER MEASURE OF SPREAD:

.

↳ Largest value in the data minus the smallest value.

minus

RANGE:

.

↳ Largest value in the data ________ the smallest value.

Standard Deviation (SD, s or σ)

UNDER MEASURE OF SPREAD:

.

↳ Represents the "average" distance from the mean.

.

↳ Degree of precision of a measurement.

distance

precision

STANDARD DEVIATION (SD, s or σ):

.

↳ Represents the "average" ____________ from the mean.

.

↳ Degree of _____________ of a measurement.

Coefficient of Variation

UNDER MEASURE OF SPREAD:

.

↳ Allows comparing SD with different units.

units

COEFFICIENT OF VARIATION:

.

↳ Allows comparing SD with different _______.

Measure of Shape

UNDER DESCRIPTIVE STATISTICS:

.

↳ Gaussian (Normal) Distribution "Bell Curve"

.

↳ 68.3% is between x̄±1SD, 95.4% is between x̄±2SD, 99.7% is between x̄±3SD.

Gaussian

68

4

99

MEASURE OF SHAPE:

.

↳ ___________ (Normal) Distribution "Bell Curve"

.

↳ ___.3% is between x̄±1SD, 95.__% is between x̄±2SD, ___.7% is between x̄±3SD.

Method Selection

Evaluation

Monitoring

3 Method of Evaluation

(MS, E, M)

Method Selection

UNDER METHOD OF EVALUATION:

.

↳ Journals (Scientific Literature)

.

↳ Product Specifications

Scientific

Specifications

METHOD SELECTION:

.

↳ Journals (______________ Literature)

.

↳ Product ___________________

Analytic Sensitivity

Analytic Specificity

Specificity

Analytic Measurement Range (AMR)

Clinically Reportable Range (CRR)

Limit of Detection (LoD)

In Blood Chemistry & Endocrinology Laboratory

7 Terms under Method Selection

(AS, AS, S, AMR, CRR, LD, IBC&EL)

Analytic Sensitivity

TERM UNDER METHOD SELECTION:

.

↳ Ability of a method to detect small quantities of an analyte.

.

↳ Refers to the lower limit of detection for a given analyte.

small

lower

detection

ANALYTIC SENSITIVITY:

.

↳ Ability of a method to detect _________ quantities of an analyte.

.

↳ Refers to the ________ limit of ______________ for a given analyte.

Analytic Specificity

TERM UNDER METHOD SELECTION:

.

↳ Ability of a method to detect only the analyte it is designed to determine.

analyte

ANALYTIC SPECIFICITY:

.

↳ Ability of a method to detect only the ___________ it is designed to determine.

Specificity

TERM UNDER METHOD SELECTION:

.

↳ Ability of a method to measure only the analyte of interest.

interest

SPECIFICITY:

.

↳ Ability of a method to measure only the analyte of ____________.

Analytic Measurement Range (AMR)

TERM UNDER METHOD SELECTION:

.

↳ Linear or dynamic range.

.

↳ Range of analyte concentrations that can be directly measured without dilution or concentration.

dynamic

concentrations

dilution

ANALYTIC MEASUREMENT RANGE (AMR):

.

↳ Linear or ____________ range.

.

↳ Range of analyte __________________ that can be directly measured without __________ or concentration.

Clinically Reportable Range (CRR)

TERM UNDER METHOD SELECTION:

.

↳ Range of analytes that a method can quantitatively report.

.

↳ Allows for dilution and concentration used to extend AMR.

quantitatively

dilution

AMR

CLINICALLY REPORTABLE RANGE (CRR):

.

↳ Range of analytes that a method can _________________ report.

.

↳ Allows for ___________ and concentration used to extend _______.

Limit of Detection (LoD)

TERM UNDER METHOD SELECTION:

.

↳ Lowest amount of analyte accurately detected by a method.

Lowest

LIMIT OF DETECTION (LoD):

.

↳ ___________ amount of analyte accurately detected by a method.

In Blood Chemistry & Endocrinology Laboratory

TERM UNDER METHOD SELECTION:

.

↳ Consider:

.

…..➙ Throughput

.

…..➙ Turnaround Time

.

…..➙ Cost

.

…..➙ Space Needs

.

…..➙ Disposal Needs

.

…..➙ Personnel Requirements

Throughput

Disposal

Requirements

IN BLOOD CHEMISTRY & ENDOCRINOLOGY LABORATORY:

.

↳ Consider:

.

…..➙ ______________

.

…..➙ Turnaround Time

.

…..➙ Cost

.

…..➙ Space Needs

.

…..➙ _____________ Needs

.

…..➙ Personnel ___________________

Determination of Imprecision

UNDER METHOD OF EVALUATION:

.

↳ Dispersion of repeated measurements about the mean due to analytic (random error).

.

↳ Random error varies from sample to sample.

.

↳ Causes:

.

…..➙ Instrument instability

.

…..➙ Temperature and reagent variation

.

…..➙ Handling techniques

.

…..➙ Operator variables

.

↳ Determined by repeated analysis study.

.

…..➙ Detects random error that affects reproducibility.

repeated

random

sample

Temperature

Handling

study

reproducibility

DETERMINATION OF IMPRECISION:

.

↳ Dispersion of ____________ measurements about the mean due to analytic (___________ error).

.

↳ Random error varies from sample to _______.

.

↳ Causes:

.

…..➙ Instrument instability

.

…..➙ ________________ and reagent variation

.

…..➙ _____________ techniques

.

…..➙ Operator variables

.

↳ Determined by repeated analysis _________.

.

…..➙ Detects random error that affects ____________________.

Repeated Analysis Study (Precision Study)

↳ 2 x 2 x 10 study

.

…..➙ 2 controls are run twice a day for 10 days.

.

…..➙ E.g., glucose in hyperglycemic (150 mg/dL) and normal range (90 mg/dL).

10

twice

normal

REPEATED ANALYSIS STUDY (PRECISION STUDY):

.

↳ 2 x 2 x ___ study

.

…..➙ 2 controls are run ________ a day for 10 days.

.

…..➙ E.g., glucose in hyperglycemic (150 mg/dL) and _________ range (90 mg/dL).

Determination of Inaccuracy

UNDER REPEATED ANALYSIS STUDY (PRECISION STUDY):

.

↳ Difference between a measured value and its true value due to systemic error (proportional or constant).

.

…..➙ Systemic Error = Always in one direction.

.

…..➙ Proportional Error = The magnitude of error is dependent on analyte concentration.

.

…..➙ Constant Error = The magnitude of error is constant and not dependent on analyte concentration.

.

↳ Can be determined by recovery study, interference study, and comparison of methods.

.

…..➙ Recovery = Ability of a test to measure a known amount of analyte (e.g. Ca2+) added to a matrix (e.g. CSF).

.

…..➙ Interference = Effect of an interferent (e.g. Hb) on the accuracy of detection of an analyte (e,g, troponin).

measured

systemic

one

analyte

constant

DETERMINATION OF INACCURACY:

.

↳ Difference between a ______________ value and its true value due to __________ error (proportional or constant).

.

…..➙ Systemic Error = Always in ______ direction.

.

…..➙ Proportional Error = The magnitude of error is dependent on ___________ concentration.

.

…..➙ Constant Error = The magnitude of error is ___________ and not dependent on analyte concentration.

Systemic Error

UNDER DETERMINATION OF INACCURACY:

.

➙ Always in one direction.

Proportional Error

UNDER DETERMINATION OF INACCURACY:

.

➙ The magnitude of error is dependent on analyte concentration.

Constant Error

UNDER DETERMINATION OF INACCURACY:

.

➙ The magnitude of error is constant and not dependent on analyte concentration.

recovery

comparison

matrix

detection

DETERMINATION OF INACCURACY:

.

↳ Can be determined by _____________ study, interference study, and __________________ of methods.

.

…..➙ Recovery = Ability of a test to measure a known amount of analyte (e.g. Ca2+) added to a _______ (e.g. CSF).

.

…..➙ Interference = Effect of an interferent (e.g. Hb) on the accuracy of ______________ of an analyte (e,g, troponin).

Recovery

UNDER DETERMINATION OF INACCURACY:

.

➙ Ability of a test to measure a known amount of analyte (e.g. Ca2+) added to a matrix (e.g. CSF).

Interference

UNDER DETERMINATION OF INACCURACY:

.

➙ Effect of an interferent (e.g. Hb) on the accuracy of detection of an analyte (e,g, troponin).

Recovery Studies

↳ Detects proportional error.

proportional

RECOVERY STUDIES:

.

↳ Detects ________________ error.

Interference Studies

↳ Detects constant error.

.

↳ Common interference:

.

…..➙ Hemolysis

.

…..➙ Lipemia

.

…..➙ Bilirubin

.

…..➙ Anticoagulant

.

…..➙ Preservatives

constant

Lipemia

Anticoagulant

INTERFERENCE STUDIES:

.

↳ Detects ___________ error.

.

↳ Common interference:

.

…..➙ Hemolysis

.

…..➙ ___________

.

…..➙ Bilirubin

.

…..➙ ________________

.

…..➙ Preservatives

Constant Error

UNDER INTERFERENCE STUDIES:

.

↳ Magnitude of error is constant and not dependent on analyte concentration.

analyte

CONSTANT ERROR:

.

↳ Magnitude of error is constant and not dependent on ________ concentration.

Comparison-of-Methods Studies

↳ Detects systemic error.

.

↳ The test method is compared with a reference method (gold standard).

.

…..➙ 40-100 specimens were run everyday over 8-20 days.

.

…..➙ A plot of the test-method data (y-axis) versus the comparative method (x-axis) is generated.

systemic

reference

20

test

comparative

COMPARISON-OF-METHODS STUDIES:

.

↳ Detects ____________ error.

.

↳ The test method is compared with a _____________ method (gold standard).

.

…..➙ 40-100 specimens were run everyday over 8-___ days.

.

…..➙ A plot of the _____-method data (y-axis) versus the ______________ method (x-axis) is generated.

Random Error

TYPES OF ERROR:

.

➙ Precision study.

Constant Error

TYPES OF ERROR:

.

➙ Interference studies.

Proportional Error

TYPES OF ERROR:

.

➙ Recovery experiment.

Systemic Error

TYPES OF ERROR:

.

➙ Comparison of methods.

Total Error

TYPES OF ERROR:

.

➙ Precision and COM.

Reference Interval

↳ Referred as reference ranges.

.

↳ A pair of medical decision points that span the limits of results expected for a given condition.

ranges

medical

limits

REFERENCE INTERVAL:

.

↳ Referred as reference _________.

.

↳ A pair of ___________ decision points that span the ________ of results expected for a given condition.

Normal Range

↳ Range of results between medical decision levels that correspond to ±2SD of results from a healthy patient.

2

healthy

NORMAL RANGE:

.

↳ Range of results between medical decision levels that correspond to ±__SD of results from a ___________ patient.

Confidence Interval

↳ Range of values that include a specific probability, usually 90% or 95%.

probability

95

CONFIDENCE INTERVAL:

.

↳ Range of values that include a specific ______________, usually 90% or ___%.

Medical Decision Level

↳ Value for an analyte that represents the boundary between different therapeutic approaches.

boundary

therapeutic

MEDICAL DECISION LEVEL:

.

↳ Value for an analyte that represents the ____________ between different _________________ approaches.

Therapeutic Range

↳ Reference interval applied to a therapeutic drug.

therapeutic

THERAPEUTIC RANGE:

.

↳ Reference interval applied to a _______________ drug.

Establishing a Reference Interval

↳ Done when there is no existing assay for an analyte or methodology in the laboratory.

.

↳ May require from 120 to ≈ 700 study individuals.

assay

methodology

700

ESTABLISHING A REFERENCE INTERVAL:

.

↳ Done when there is no existing ________ for an analyte or ______________ in the laboratory.

.

↳ May require from 120 to ≈ ______ study individuals.

Verifying a Reference Interval (Transference)

↳ Confirm the validity of an existing reference interval for an analyte using the same type of analytic system.

.

↳ Can require 20 study individuals.

validity

system

20

VERIFYING A REFERENCE INTERVAL (TRANSFERENCE):

.

↳ Confirm the __________ of an existing reference interval for an analyte using the same type of analytic _________.

.

↳ Can require ___ study individuals.

Clinical Sensitivity

↳ Proportion of individuals with that disease who test positively with the test.

Proportion

positively

CLINICAL SENSITIVITY:

.

↳ ________________ of individuals with that disease who test ____________ with the test.

True Positive

↳ Patient with a condition who are classified by a test to have the condition.

test

TRUE POSITIVE:

.

↳ Patient with a condition who are classified by a _______ to have the condition.

False Negative

↳ Patient with a condition who are classified by a test as not having the condition.

not

FALSE NEGATIVE:

.

↳ Patient with a condition who are classified by a test as _____ having the condition.

Diagnostic Sensitivity

Diagnostic Specificity

Positive Predictive Value

Negative Predictive Value

4 Measures of Diagnostic Efficiency

(DS, DS, PPV, NPV)

Diagnostic Sensitivity

MEASURES OF DIAGNOSTIC EFFICIENCY:

.

↳ Ability of a test to detect a given disease or condition.

.

↳ TP / TP + FN

disease

TP

DIAGNOSTIC SENSITIVITY:

.

↳ Ability of a test to detect a given ____________ or condition.

.

↳ ____ / TP + FN

Diagnostic Specificity

MEASURES OF DIAGNOSTIC EFFICIENCY:

.

↳ Ability of a test to detect the absence of a given disease or condition.

.

↳ TN / TN + FP

absence

FP

DIAGNOSTIC SPECIFICITY:

.

↳ Ability of a test to detect the ____________ of a given disease or condition.

.

↳ TN / TN + ____

Positive Predictive Value

MEASURES OF DIAGNOSTIC EFFICIENCY:

.

↳ Refers to the probability of an individual having the disease if the result is outside the reference range.

.

↳ TP / TP + FP

disease

outside

TP

POSITIVE PREDICTIVE VALUE:

.

↳ Refers to the probability of an individual having the __________ if the result is __________ the reference range.

.

↳ TP / ___ + FP

Negative Predictive Value

MEASURES OF DIAGNOSTIC EFFICIENCY:

.

↳ Refers to the probability that a patient does not have a disease if the result is within the reference range.

within

NEGATIVE PREDICTIVE VALUE:

.

↳ Refers to the probability that a patient does not have a disease if the result is __________ the reference range.

Quality Control.

↳ Check the reproducibility of a method by including control specimens in the run.

.

…..➙ Equipment out of calibration.

.

…..➙ Reagent may be deteriorating.

.

…..➙ Technologist may have made an error.

.

↳ Done by running QC materials (Controls)

.

…..➙ Should be the same as the specimens to be tested;

.

…..➙ Should span the clinically important range of the analyte (cutoff values);

.

……..● I.e. Glucose Assays

.

……….○ In Reference Range (80 mg/dL)

.

……….○ Hypoglycemia (50 mg/dL)

.

……….○ Hyperglycemia (150 mg/dL)

.

↳ Types of Controls

.

…..➙ Lyophilized (Dehydrated Powder)

.

……..● Reconstituted with its diluents.

.

…..➙ Stabilized Frozen Controls

.

……..● Needs to be evaluated for stability.

reproducibility

control

calibration

Reagent

error

Running

same

range

Glucose

50

150

QUALITY CONTROL:

.

↳ Check the _____________________ of a method by including ________ specimens in the run.

.

…..➙ Equipment out of _______________.

.

…..➙ _____________ may be deteriorating.

.

…..➙ Technologist may have made an ________.

.

↳ Done by ___________ QC Materials (Controls)

.

…..➙ Should be the ________ as the specimens to be tested;

.

…..➙ Should span the clinically important ___________ of the analyte (cutoff values);

.

……..● I.e. __________ Assays

.

……….○ In Reference Range (80 mg/dL)

.

……….○ Hypoglycemia (____ mg/dL)

.

……….○ Hyperglycemia (_____ mg/dL)

Lyophilized

diluents

Frozen

evaluated

QUALITY CONTROL:

.

↳ Types of Controls

.

…..➙ _____________ (Dehydrated Powder)

.

……….● Reconstituted with its __________.

.

…..➙ Stabilized __________ Controls

.

…..,,,..● Needs to be _____________ for stability.

Levey-Jennings Control Chart

QUALITY CONTROL (QC) CHARTS:

.

↳ Used to detect errors (inaccuracy and imprecision) over time.

.

…..➙ Random Errors = Due to variations in technique.

.

…..➙ Systemic Errors = Poorly made (contaminated) standards and reagents; instrumentation problems (function and calibration); poorly written procedure.

.

↳ Control values should be within statistical limits (expressed as the mean ±SD).

errors

variations

contaminated

function

procedure

statistical

mean

LEVEY-JENNINGS CONTROL CHART:

.

↳ Used to detect ________ (inaccuracy and imprecision) over time.

.

…..➙ Random Errors = Due to ____________ in technique.

.

…..➙ Systemic Errors = Poorly made (_________________) standards and reagents; instrumentation problems (__________ and calibration); poorly written ______________.

.

↳ Control values should be within _____________ limits (expressed as the _______ ±SD).