Advanced TB Diagnostic Research, 2012

An intensive, high-level course on TB diagnostic research methods


University of Cape Town (6-9 March 2012)

Course Slides

Day 1 (6 March 2012)

The global value chain for TB diagnostics and current pipeline - M Pai [Link]
Value chain in action: Xpert MTB/RIF - M Nicol [Link]
Beyond Xpert: What will the future look like? - K Dheda [Link]
Value chain in action: TB serological tests - M Pai [Link]
Types of diagnostic designs and landscape of TB dx research - M Pai [Link]
Evaluation of reproducibility and reliability of TB diagnostics - R van Zyl-Smit [Link]
Incremental value of new diagnostics: an overview - M Pai [Link]
Incremental value: case study: IGRAs in HIV+ patients - M Rangaka [Link]

Day 2 (7 March 2012)

Impact of test results on diagnostic thinking and clinical decisions: an overview - M Pai [Link]
POC testing - M Pai [Link]
Reference standards: Brief presentations & panel discussion
-- Microscopy studies - A Whitelaw [Link]
-- Molecular assays - M Nicol [Link]
-- LTBI tests - M Pai [Link]
-- Pediatric TB - H Zar [Link]
-- Extrapulmonary TB - J Peter [Link]
Diagnosis of TB end-points in vaccine trials: methodological issues - H Mahomed [Link]
Evaluation of TB biomarkers: methodological issues - W Hanekom [Link]
Impact on patient outcomes: intro to diagnostic RCTs - M Pai [Link]
Diagnostic RCTs: case study: Xpert MTB/RIF - G Theron [Link]

Day 3 (8 March 2012)

Systematic reviews & meta-analyses of diagnostic accuracy - M Pai [Link]
SR: case study 1: Oral fluid vs blood-based HIV testing - N Pant Pai [Link]
SR: case study 2: Predictive value of IGRAs - M Rangaka [Link]
Guideline development in TB diagnostics - M Pai [Link]
Operational and implementation research: an overview - M Pai [Link]
Implementation research: case study 1: Improving case detection in HIV-infected persons - S Lawn [Link]
Implementation research: case study 2: Optimizing specimen collection in children - H Zar [Link]
Implementation research: case study 3: Optimizing urine-based diagnostics - J Peter [Link]

Day 4 (9 March 2012)

Modeling of TB diagnostics - P Uys [Link]
Cost-effectiveness analyses - E Sinanovic [Link]
Panel Discussion: Getting your study published! - M Pai, K Dheda, S Lawn, R Wilkinson [Link]
Raising funds and finding mentorship - R Wilkinson [Link]
Feedback and closure - M Pai


Context
High quality diagnostic studies are critical to evaluate new tools, to develop evidence-based policies on TB diagnostics. There is evidence that TB diagnostic trials are poorly conducted and poorly reported. Lack of methodologic rigour in TB trials is a cause for concern as it may prove to be a major hurdle for effective application of diagnostics in TB care and control. Furthermore, there is evidence that a majority of TB diagnostic studies are focused on test accuracy. There are limited data on outcomes such as accuracy of diagnostic algorithms (rather than single tests) and their relative contributions to the health care system, incremental value of new tests, impact of new tests on clinical decision-making and therapeutic choices, cost-effectiveness in routine programmatic settings, and impact on patient-important outcomes. This poses problems because research on test accuracy, while necessary, is not sufficient for policy and guideline development. Test accuracy data are surrogates for patient-important outcomes and cannot provide high quality evidence for policy making. Therefore, accuracy studies must be considered along with impact of the test on patient-important outcomes, and other factors such as quality of the evidence, the uncertainty about values and preferences associated with the tests and presumed impact on patient-important outcomes, and cost and feasibility. Translation of policy into impact requires collecting evidence for scale-up, country-level data on cost-effectiveness and feasibility, implementation research, and local decisions on scale-up, delivery and impact assessment.

Course Content
This advanced course will cover the principles behind diagnostic research, diagnostic study designs, sources of bias, and value chain for TB diagnostics development. Also, critical appraisal of diagnostic studies, and conventional and advanced methods for systematic reviews (meta-analyses) of diagnostic tests will be presented, along with the GRADE approach to diagnostic policies. More recently, there is growing appreciation that "test accuracy research" focused on sensitivity and specificity is not necessarily the same as "diagnostic research." There is also a clearly felt need to go beyond test accuracy and evaluate accuracy of diagnostic algorithms (rather than single tests) and their relative contributions to the health care system, incremental value of new tests, impact of new tests on clinical decision-making and therapeutic choices, cost-effectiveness in routine programmatic settings, and impact on patient-important outcomes. This course will introduce multivariable approaches to diagnostic research, and cover alternative designs which evaluate patient outcomes, including the diagnostic RCT, and implementation research. The course will also cover mathematical modelling, costing and cost-effectiveness studies.

Cape Town: For more information, click here.