Advanced Tuberculosis Diagnostic Research, 2013
Montréal

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

Course Slides

Day 1 (8 July 2013)
Global value chain, pipeline, POC testing; TB diagnostics development

The global value chain for TB diagnostics - M Pai [Download]

Data to scale-up: building the evidence base for new Dx - M Kimerling [Download]

Scale-up of Xpert MTB/RIF: SA roll out - L Berrie & S Molapo [Download]

Replacing suboptimal with WHO-endorsed tests in India - M Pai & M Kaur [Download]

Beyond Xpert: fast-followers and NAAT pipeline - D Boyle [Download]

POC testing – definitions, TPPs and barriers - M Pai [Download]

Day 2 (9 July 2013)
Market research, incremental value, diagnostic thinking impact, reference standards, imperfect gold standards; RCTs and patient impact

Market-based approaches in TB diagnostics - J Ginnard [Download]

What is the market for TB diagnostics? - P Chedore & S Kik [Not Available]

Reference standards: Microscopy studies - L Davis[Download]

Reference standards: Molecular assays – P Nabeta[Download]

Reference standards: IGRAs – D Menzies[Download]

Reference standards: Pediatric TB – A Ahmed[Download]

Reference standards: Extrapulmonary TB – G Fox[Download]

Statistical approaches for dealing with imperfect reference standards - N Dendukuri [Download]

Importance of reproducibility: case study of IGRAs - N Banaei [Download]

Incremental value of new diagnostics - M Pai [Download]

Impact of test results on diagnostic thinking - M Pai [Download]

Impact on patient outcomes: diagnostic RCTs in TB - L Davis [Download]

Day 3 (10 July 2013)
Implementation research; qualitative research

Measuring clinical impact without randomization: methodological issues - L Davis [Download]

Maximizing the impact of smear microscopy - L Davis [Download]

Qualitative research on TB diagnostics - N Engel [Download]

Xpert MTB/RIF: challenges in low incidence settings - C Denkinger [Not Available]

Xpert MTB/RIF in high incidence settings: XTEND study - V Chihota [Not Available]

Where to place diagnostics for maximum impact? - K Palamountain [Not Available]

Are microscopy centers ready for molecular tests? – C Denkinger [Download]

Day 4 (11 July 2012)
Meta-analysis, GRADE, guidelines, modeling

Systematic reviews of diagnostic accuracy - K Steingart [Download]

SR: case study: Xpert for EPTB - C Denkinger [Not Available]

SR: case study: Predictive value of IGRAs - S Kik [Download]

Guideline development in TB diagnostics - K Steingart [Download]

Prequalification of diagnostics, quality assurance and procurement - A Sands [Download]

Mathematical modeling: an introduction - D Dowdy [Download]

Day 5 (12 July 2013)
Modeling, cost effectiveness

Modeling of TB diagnostics: evaluating new tools - D Dowdy [Download]

Modeling of TB diagnostics: evaluating the diagnostic process - D Dowdy [Download]

Introduction to cost-effectiveness analysis - D Dowdy [Download]

Cost-effectiveness case study: Triage testing for TB - A van’t Hoog [Not Available]

Cost-effectiveness case study: Diagnostics for HIV-associated TB - D Dowdy [Download]

“User-friendly” modeling: introduction, pros and cons - D Dowdy [Download]

Modeling and cost-effectiveness: a synthesis - D Dowdy [Download]

Course Description [Link]

Registration Form [Link]

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, 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 latent class analysis, mathematical modeling, costing and cost-effectiveness studies. Panel discussions will cover topics such as market analyses, market dynamics, regulatory issues, target product profiles, and industry engagement in TB diagnostics development.

Objectives

By the end of the course, participants will understand:

  • the value chain for TB diagnostics development, current pipeline of diagnostics, market dynamics, WHO policies on new diagnostics, and challenges for scale-up
  • principles and practice of diagnostic research focused on accuracy of tests
  • principles of multivariable approaches to diagnostic research, and adjustment for imperfect reference standards
  • principles of meta-analyses of diagnostic accuracy studies and GRADE approach to diagnostic policies
  • principles of alternative designs to evaluate impact of new tests on clinical decision-making, therapeutic choices, and patient-important outcomes
  • principles of implementation research, collecting evidence for scale-up, cost-effectiveness analyses and modeling studies in TB diagnostics