What do clinicians need from a laboratory test?

Ola H. ElgaddarMD, PhD, MBA, CPHQ, LSSGB

Lecturer of Chemical Pathology Medical Research Institute

Alexandria UniversityOla.elgaddar@alexu.edu.eg

Does it have the

right tests??

Is he a patient??

Is it correct??

In this context, what is meant by:

ØDoes the lab request have the “right” tests??

ØIs this person a “patient”??

Diagnostic (Clinical) Performance

ØIs it a “Correct” Result??- Accredited lab (ISO 15189 – CAP – JCI)- Quality Management System (QMS)

Pre-analyticalAnalyticalPost-analytical

- Errors- Uncertainty

Analytical Performance

There are two arms for lab test performance, and both should be equally considered:

ØAnalytical PerformanceØDiagnostic Performance

Analytical Performance

Quality

Doing the right thing right, from the first time and every time!

Accreditation

An institution or a program meets standards of quality set forth by an accrediting agency

In a medical lab, there are 3 main stages:

1) Pre-analytical2) Analytical3) Post-analytical

All of them should be under tight control

1) Pre-analytical

• Patient & specimen identification• Patient preparation • Specimen collection, transport and handling• Monitoring personnel

2) Analytical

The 5 Ms???qMachine (Technology)qMethod (Selection / Evaluation)qMaterial (Reagents)qMan Power (Training)qMeasurement (IQC & EQC)

3) Post - Analytical

ØTranscriptional errorsØMissed flags

LIS is a radical solution

Almost!!!

Evaluation of a Laboratory

Method

Validation / Verification??Method validation: (Manufacturer)

Establishing the performance of a newdiagnostic tool

Confirmation, through the provision ofobjective evidence, that the requirements fora specific intended use or application havebeen fulfilled’ (doing correct test)......ISO 9001:2005

Validation / Verification??Method verification: (Lab / User)

A process to determine performancecharacteristics before a test system is utilizedfor patient testing.

Confirmation, through the provision ofobjective evidence, that specifiedrequirements have been fulfilled’ (doing testcorrectly)……ISO 9001:2005

The following items need verification

ØAnalytical Specificity: Interference studiesØAnalytical Sensitivity: Calibration curve

Detection limitØReportable range: Linearity experimentØPrecision: Replication studyØAccuracy: Bias / Recovery studyØReference Intervals

Analytical SpecificityThe ability of an analytical method to detect

“ONLY” the analyte of interest.

Freedom from interference by any element or compound other than the analyte of interest

Analytical Sensitivity- The ability of an analytical method todetect a low concentration of a givensubstance in a biological sample. The lowerthe detectable concentration, the greaterthe analytical sensitivity.- Detection limits studies

??

Reportable Range=

Analytical Measurement Range

It is the range of numeric results a method can produce without any special specimen pre-treatment, such as dilution.

PrecisionCloseness of agreement between quantity values obtained by replicate measurements of a quantity, under specified conditions.

AccuracyCloseness of the agreement between theresult of a measurement and a true value ofthe measurand.

Reference intervalsØEach lab should establish its ownreference intervals regarding the populationthat it serves.ØReference ranges differ by age, sex andethnic group.ØThe lab should report the appropriatereference range with each released result,otherwise, the clinician will not be able tointerpret the result.

Reference intervalsExample:TSH of an infant (1 month old) is 5uU/mLIf the lab reports the reference range ofadults with the result (0.4 – 4), this resultwould be abnormal!

If the correct reference range for age wasreported (1 – 7.9), this result is completelynormal.

Internal Quality Control (IQC) is used, on dailybasis, in the decision to accept or rejectresults of patients samples and enables thelab to describe and monitor the quality of itswork.-Usually it has 2 levels (Sometimes 3);representing the “Normal” and the“Pathological” analyte level.

External Quality Control (EQC) =Proficiency test is used, on monthly or Bi-weekly (Or others) basis, where labs from allover the world join the program and send theirused Method / Analyzer.- A statistical comparison is made and eachlab result is compared to the result of its peergroup in each analyte.

Types of Laboratory errors

Ø Random error, RE, or imprecision isdescribed as an error that can be eitherpositive or negative, whose direction andexact magnitude cannot be predicted,where the distribution of results whenreplicate measurements are made on asingle specimen.ØUsually, due to error in Pipetting

Types of Laboratory errors

Ø Systematic error, SE, or inaccuracy is anerror that is always in one direction,displacing the mean of the distribution fromits original value.ØIn contrast to random errors, systematicerrors are in one direction and cause all thetest results to be either high or low.ØEither constant or proportionateØUsually, due to error in calibration

UncertaintyØ It is an interval around a reportedlaboratory result that specifies the location ofthe true value with a given probabilityØ It takes into consideration both theimprecision (SD), and the inaccuracy (Bias)Ø Should be reported to the clinician, or atleast be available upon request!ØExample: Lab XYZ reports blood glucoselevel with 6 % uncertainty

(i.e: Result +/- 6%)

Diagnostic(Clinical)

Performance

Clinical utility of a lab test refers to its abilityto differentiate between diseased and non-diseased persons.

The ideal tests has both diagnosticsensitivity and specificity equal 100 %

But actually, no test is ideal!!

When sensitivity increases, specificitydecreases and vice versa.

Depending on the clinical utility, theappropriate test is selected; if we arescreening population, then we need a test ofhigh sensitivity (You do not want to miss asingle case, even if you got false positivecases).Ex: Occult blood in stool as a screening toolfor cancer colon

SUMMARYØ The clinician should know the Clinicalperformance of each test before ordering it;bad test selection gives a bad result that isnot useful in the diagnosis.

Ø The lab doctor should measure theAnalytical performance of lab tests, shouldensure its validity and should provide suchdata to the clinician

THANKYOU