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Introduction: 3 phases of study design
Laboratory
phase
- develop test
- test with few
cases and healthy
controls
- prove of concept
Case-control
phase
- test with definite
cases and definite
controls
- calculate
Se & Sp
Prospective
phase
- test with disease-
suspected
patients
- calculate Se, Sp,
PPV & NPV
Introduction: 3 phases of study design
Laboratory
phase
- develop test
- test with few
cases and healthy
controls
- prove of concept
Case-control
phase
- test with definite
cases and definite
controls
- calculate
Se & Sp
Prospective
phase
- test with disease-
suspected
patients
- calculate Se, Sp,
PPV & NPV
Look promising
Introduction: 3 phases of study design
Laboratory
phase
- develop test
- test with few
cases and healthy
controls
- prove of concept
Case-control
phase
- test with definite
cases and definite
controls
- calculate
Se & Sp
Prospective
phase
- test with disease-
suspected
patients
- calculate Se, Sp,
PPV & NPV
Look promising Look good
Introduction: 3 phases of study design
Laboratory
phase
- develop test
- test with few
cases and healthy
controls
- prove of concept
Case-control
phase
- test with definite
cases and definite
controls
- calculate
Se & Sp
Prospective
phase
- test with disease-
suspected
patients
- calculate Se, Sp,
PPV & NPV
Look promising Look good Look rubbish(GS problem)
Good guideline
• Recommendation 1: Access index test’s ability to predict patient-relevant outcomes instead of test accuracy
• Recommendation 2: Access the concordance of difference tests instead of test accuracy
• Recommendation 3: Qualify the interpretation of “naïve” estimates of the index test’s performance
• Recommendation 4: Imperfect gold standard model
Recommended design for melioidosis
• Define need For example, estimate Se, Sp, PPV and NPV in a prospective
design (to represent the real clinical situation)
• Define study population (that we would like to infer the estimated accuracy to)
• Next: select reference standard
Recommended design for melioidosis
• If there are more than one population, at least 2 diagnostic tests (3 tests are preferred)
Those 2 tests should be based on 2 different biological mechanism (e.g. one antigen detection [culture] and one antibody detection [IHA])
• If there is only one population, at least 3 diagnostic tests (5
tests are preferred)Those 3 tests should be based on 3 different biological mechanism (e.g. one antigen detection [culture / PCR assays], one antibody detection [IHA/ELISA], one clinical detection [ultrasonogram/CT scan])
Recommended design for melioidosis
• Consider repeated sampling and convalescent specimens• Day 4 and Day 7 specimens may have clinical implication for
changing the diagnosis and treatment • Day 14 and Day 28 specimens may have clinical implication for
starting oral treatment regimen• Consider long-term outcome for relapse/recurrent infection
• Four-fold rising is arbitrary and based on imperfect gold standard. This should be evaluated with better approach
• Adequate sample size is required (enough diseased patients for sensitivity estimation is important than the total number)
Recommended design for melioidosis
• Select sites• Appoint study team• Train staff• Provide GCP• Conduct QC and monitoring• Collect data • Perform analysis • Report results using STARD checklist• Disseminate results