Topic 11: Automation, Lab Information Systems and AI; Point-of-Care Testing, Interferences and Diagnosis

What drives increasing automation?

• decreasing government reimbursement

• increased consumable costs

• high labour cost

• availability of staff

• economy of scale

Centralisation of lab facilities

• increased vol of testing

• need automation to cope

Risk of litigation

• improve quality

• reduce human error

• most errors at front end

Lab safety

• infectious disease risk: HIV, hepatitis, Ross River, Hendra

What are the advantages to automation?

• Economic

  • cost of automation vs cost of labour

  • allows redeployment of staff to worthwhile tasks

• Strategic

  • improvement in TAT (turn around time)

  • allows for future expansion without extra costs

• Quality

  • reduction in human errors

  • objective monitoring of error

• Safety

  • less exposure of lab staff to specimens

What are the disadvantages to automation?

• Economic

  • capital outlay

  • potential increase in consumable costs

• Strategic

  • dependency on automation without extensive backup

  • increased dependency on LIS

• Quality

  • decreased human surveillance

  • potential for large scale errors

What are the characteristics of automated analysers

• detectors, photometer, spectrophotometer, fluorimeter, luminometer

• positive displacement pipetting 

• mixing: dispensing, magnetic, mechanical 

• peltier heating: water bath, oil bath, block 

• on board reagent storage

• reagent and specimen barcode

• reaction vessel, disposable cuvettes

What is the definition of QC, Quality Assurance and Quality Assessment?

Quality Control

• refers to the measures that must be included during each assay run to verify that the test is working properly

Quality Assurance

• defined as overall program that ensures the final results reported by the lab are correct

Quality Assessment

• proficiency testing determines quality of lab results. quality assessment challenges effectiveness of QA and QC

What is involved in the RCPA/AACB Quality assessment program?

regular assessment for participants

• 2 samples for analysis 

• every 2 weeks or monthly

• cover expected patient range

• assessment based on standard analysis required for patient care 

Describe Specimen Data Entry

• data entry made for each specimen in LIS

• must record all relevant patient info and results of lab testing

• entries ensure that rseults can be verified and associated QC

What info should be in specimen data entries?

• patient name + unique identifier

• patient lab ID

• contact details of requester

• type of primary specimen

• date of specimen collection

• date of specimen reception

• date of specimen acceptance

• tests requested

• results of tests + name of lab scientist performing test

• date of reporting

• ID of person sending report

A LIS entry should…?

• display and correlate all test results: a combo of results = more diagnostic for specific disease and more informative than single results

• historical medical records of specific patients: correlating requested test result with patient medical records

• monitoring of TAT during testing

• investigate the positivity rate for specific tests: used for surveillance of disease development or requester behaviour

How does LIMS support quality management

• tracks samples and manages QC data

• software automates data collection, monitor trends, and analyse QC data

• logs of QC data improve storage, trend ID and organisation, and aid efficient QC management 

• management softward includes:

  • root cause analysis helps to ID source of QC failure so corrective and preventative actions can be implemented

  • method validation of new test methods ensure they meet performance standards

  • QC software helps monitor real-time data

  • reagent management of stock levels, ordering and replenishment to minimise errors 

• greater reliability and consistency in testing by incorporating quality management in correlation with Levey Jennings and Westgard rules

NATA: assessing AI opportunities

how is AI managed in MLS?

• requirements for verification, validation, data control, organised governance, accountability 

• NATA standards and guidelines leading lab AI implementation

• standards for AI testing and validation in MLS

• AI management system certification standard ISO 42001

What is the goal of ISO 420001?

help organisations establish structural, ethical, and transparent AI systems that build customer trust and mitigate risks

What is the definition of POCT? Where, who and why is it performed?

• tests performed outside clinical lab

• where: patients home/work/medical pracs office/surgical theatre

• who: nurses, therapists, anaesthetists, surgical staff

• why: local, immediate, cheap, frequency

Why is POCT used as an alternative to POCT?

• testing comes directly to patient

• decentralisation of testing

• increased interaction w patient

• cost benefit

• immediate result 

• increased freq of monitoring

• decreased use of specialised staff

What are the requirements of POCT devices

• whole blood samples

• minimum or NO sample volume

• fast TAT

• robust 

• long lifetime

• easy and inexpensive to manufacture

Describe the POCT: pregnancy test strip

• detects hCG produced by placenta during pregnancy

• hCG excreted in mothers urine

• use lateral immunoassay

What should be considered when developing POCTs

• calibration and QA

• data handling

• staff training

• cost effectiveness

• outcomes

• comparable results to central lab

• low-maintenance

• user friendly

• compact and portable

• integration of patient results into records

Is the quality of POCT comparable to testing carried out in central lab?

can provide comparable answers if:

• users are trained

• QC procedures are followed

• results are integrated into patient record

what is the true cost of POCT?

• varies depending on context - incl type of test, setting and resource availability 

• need to prvent POCT duplicating centralised testing

does POCT lead to better patient outcomes?

• reduced TAT

• quicker treatment

• improved patient outcome

What is the ideal POCT?

• non-invasive, multi-analyte sensor

What are some interference errors in testing? include endogenous and exogenous

Definition: interference occurs when substance falsely alters test result 

endogenous: interfering substance is present in patient specimen 

exogenous: interfereing substance is introducted into patient specimen through pre-analytical or analytical processes

What are the Major causes of interferences

• haemolysis, icterus, lipaemia

• bilirubin

• drugs

• antibodies

Decribe when and how haemolysis can interfere with clinical biochem results? what kind of interference is it?

• specimen collection and processing

• endogenous

• additive - addition of RBC constituents 

• spectral 

• chemical - cross reaction of RBC constituents with assay: adenylate cyclase in CK assay

• dilutional - intracellular fluid dilates specimen constituents 

Decribe how jaundice can interfere with clinical biochem results? what kind of interference is it?

• increased bilirubin

• endogenous

• interferences at bilirubin >500unol/L

• spectral 

• chemical - cross reaction with peroxidase reactions give decreased result 

  • cross react with jaffe reaction for creatinine to give decreased result

Decribe how lipaemia can interfere with clinical biochem results? what kind of interference is it?

• increased lipid 

• increased turbidity gives increased absorbance for all spectro tests

• increased lipid gives apparent conc because of aqueous volume displacement in ion-specific measurements

How can drugs interfere with clinical biochem results? what kind of interference is it?

• drugs, herbal remedies, skin disinfectants, contrasts media, IV infusions

• exogenous

• N-acetylcysteine treatment of paracetamol OD gives decreased serum creatinine

Decribe how immunologic Abs can interfere with clinical biochem results? what kind of interference is it?

• endogenous 

• IgM or IgG 

• increased paraprotein precipitation → gives increased apparent concentration because of aqeous vol displacement in ion-specific measurements 

• heterophile Abs are polyspecific, low affinity that cross-react and interfere → remove with blocking tubes

• human anti-animal Abs (HAAA) cross react with animal (mouse) capture or detection Abs

• autoAbs aginst endogenous constituents to produce macro-Ab-Ag-complex

What defines a reference range? Who are the people who meet criteria for good health:

• range of values for a biochemical test found in “healthy” subjects against which patient values can be compared

• people who meet criteria for good health

  • no known health problems

  • ambulatory 

  • not on any regular med regime 

  • weight within recommended norms

• artificial concept - no clear boundaries

Sample numbers required for a reference range?

• the IFCC and NCCLS protocols typically suggest a minimum of 120 reference indivs for each sample or subgroup

• example, testosterone:

  • this hormone is gender dependent

  • to establish a reference interval for testosterone the lab would need results from 240 reference samples (120 men and 120 women)

what is a possible exclusion criteria for RR selection?

• risk factors

  • obesity

  • hypertension

  • genetically determined risk

• specific physiological states

  • pregnancy

  • excessive exercise

• disease

• intake of pharmacologically active agents

  • drug treatment for disease

  • oral contraceptives

  • alcohol, nicotine

Describe the 4 types of disease biomarkers in blood?

1. diagnostic biomarker: presence of disease

2. risk biomarker: risk of disease dev

3. prognostic biomarker: progress of disease

4. predictive biomarker: patient response to treatment

What is the acute phase response? What markers are indicative

• local acute inflam 

• HPA → cortisol → liver → Acute phase protein prod

• IL-6, TNF, IL-1, CRP

What are the clinical uses of CRP? What is the normal conc?

• mediate normal conc of CRP = 0.8mg/L

• non specific biomarker used for disease screening 

• detect inflam disorders → RA, IBD

• detect infection → neonatal, postop, bacterial>viral

• detect tissue injury or neoplasia → MI, tumours

• aid in DDx of inflam vs non inflam condition

What is sensitiivty and specificity?

sensitivity

• measure of test giving pos test result for true pos patients with disease

specificity 

• measure of test giving neg test for true neg patient without disease

Describe the CRP test (Roche Latex test)

principle: particle enhanced turbidimetric assay 

• uses serum or plasma and detects inflam, infection, trauma, malignancy 

1. latex particles coated with CRP specific antibodies 

2. add with patient serum containing CRP 

3. agglutinates forming large latex and CRP complexes 

4. measured on automated analyser