2.3 Selection of methodology

Question 1

What factors do you consider before selecting a method?

variance
new test, new method, change in methods

Answer 1

1) clinical need/scientific validity
- customer want- depends on what type of lab we are
- cost effective ?
- literature search - performance characteristics of new method (literature, conference, manufacturer, QAP) /available testing method
- talk to colleagues /professional bodies/guidelines

2) Pre-analytical
- specimen collection, transport, workflow

3) Analytical
- kit (controls, calibrators)
- instrument (new or already existing?)
- operator expertise

4) Post analytical
- LIS interface
- interpretation/reporting

Other

• validation difficult?
• • RR, MOU, TAT
• cost/benefit analysis
• legislative
• billing
• EQAP
• safety

LINK with

• Validation
• • request kits
• • compatibility w existing/IT/physical
• validation/analytical principles
• parallel testing

Implementation

6) staff training
7) communication
8) documentation
- SOP
- scope of practice
- - policy on alfter hours

Question 2

What are some of the reasons you may want to introduce a new test?

Answer 2

1. New assay
   - new technology
   - new development in diagnosis/management
   - increased demand/specialist request
   - new expertise in lab
2. Replacing old with new assay
   - underperformance of old
   - increased request/demand
   - TAT
   - equipment issues
   - labour intensive
   - safety profile
   - supplier withdrawal/issues
3. High sendaway costs bring in house

Question 3

You are changing tTG IgA from ELISA to ImmunoCAP. Explain the steps you would take to change methods.

Answer 3

1. Both validated methods, so need comparative validation rather than full
   - the reference method is ELISA and new is Immunocap
2. Need to find samples
   - known concentrations run on ELISA
   - follow kit insert for handling/storage/transport
   - old known, QAP samples
3. Method
   - immunocap kit insert
   - controls/1st/3rd party, LJ chart 20points for cv/sd
   - sensitivity/specificity/ accuracy/precision check, ? RR- transfer 20 samples min
   - linear regression , bland altman
   - MOU
4. Post analytcail
   - LIS/interface
   - comments
5. Other
   - SOP
   - staff training/education
   - communication
   - parallel testing for a while
   - sign off principale, director, quality manger

Question 4

What assays might be used to measure cytokines?

Answer 4

ELISA
Bead array/Luminex
Flow cytometric beads
Intracellular/functional assays

Question 5

What is your approach for changing methods? quantitative assay

ie change CH100 RID to ELISA

• statistical comparison
• how to create Bland Altman
• shown Bland Altman

Answer 5

-

Question 6

What are some of the issues related to sendaway testing?

Answer 6

• slower TAT; transport
• less control
• • handling
• • processing
• • urgency
• • reporting
• • blind analytical process
• QAP performance of the lab
• billing
• slower communication if issues, delays
• sample loss issues

Question 7

Clinician wants antibody for a rare condition X - approach

Answer 7

1. Investigate
   - take seriously
   - enquire more about condition/antibody utility/references
   - if currently any labs performing this NATA accredited
   - get back to him
2. Further investigation
   - literature
   - colleagues
   - conferences/guidelines/position statements
   - - available platforms, utility, performance characteristics
   - viability: re numbers/costs
3. Decide it is worth VS not
   - IVD in house registration with TGA
   - demand vs cost

IF deciding to go ahead
- pre analytical
-- samples suitability
- analytical
-- platform
-- controls/calibrators
- post analytical elements of assay development
-- QAP
--RR
-- validation
Difficult

Question 8

Considerations for a new platform- apparoach

Answer 8

1. Investigate
   - clinical utility vs YES/no vs IVD
   - research literature, colleagues, conf papers
   , EQAP, other labs
2. Technical specifications
   - pre analytical sampling handling, aliquoting
   - analytical methodology/characteristics, random access, automated, throughput, workflow, ease of use, staff expertise, physical aspects, maintenance/servicing, test menu
   - post analytical: LIS bidirectional interface, reporting format
3. Other
   - safety/waste
   - legislative
   - billing
   - cost/benefit analysis- reagents rental/lease
   - EQAP
4. business case
5. Implementation
   - parallel, kits validation
   - SOP
   - training
   - NATA update
   - communication to users

Question 9

What are some of the specific challenges of setting up an obscure, rare test in house?

Answer 9

Selection of methodology/clinical utility - diff to talk to colleagues, no EQAP, only published material

Technical specifications- establishing pre analytical, analytical- controls hard to source, nil ref material for calibration, diff w interpretation, set up RR, cut off that is significant

Other EQAP /sample exchange difficult, billing wont occur, legislatively need class 3 NATA unless class 4 quite rigorous need full validation