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Activities Diagnostic Tools Initiative
Activities Diagnostic Tools Initiative
| Diagnostic Tools Initiative |
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PROVE IT: (Policy Relevant Outcomes from Validating Evidence on ImpacT) StudiesThe pipeline of new diagnostic tools for TB has rapidly expanded over the last few years. A number of new tools have recently been recommended or are expected to be recommended by WHO. Most research being presented to WHO guideline committees focuses on the performance (accuracy) of new tools with some information being available on laboratory infrastructure and needs. To be able to decide whether a tool is suited for a particular context and what infrastructure is needed for its implementation and scale-up, more complex information is needed. Tools may perform differently in different epidemiological settings or within patient risk groups. A new tool is never implemented “on its own” but rather within existing diagnostic algorithms, which may differ in different settings. Laboratory structures vary in different national settings. Above all, patient access to diagnosis and related costs will impact whether a new tool will truly be able to bring the anticipated change in outcomes. In the blueprint Pathways to Better Diagnostics for Tuberculosis published in 2009 by the New Diagnostics Working Group of the Stop TB Partnership, an impact assessment framework was suggested to enable a comprehensive approach to evaluate new TB diagnostic tools. Led by TREAT TB partner Liverpool School of Tropical Medicine, this approach is being applied in TREAT TB field evaluations of new diagnostics to translate the framework into a research approach to provide important evidence and policy-relevant information related to new tools. TREAT TB partners have adopted the name PROVE-IT (Policy Relevant Outcomes from Validating Evidence on ImpacT) to refer to this research approach. It will then be further improved and presented to the TB community as a model for assessing new diagnostic tools for TB. The first field evaluation will focus on Line Probe Assays (LPA).
PROVE IT Line Probe Assays (LPAs) Field Evaluation StudyA global priority is to determine the effectiveness and applicability of diagnostic tools used to diagnose multi-drug resistant tuberculosis (MDR-TB) in various settings. Line Probe Assays (LPAs) have recently been recommended by WHO for the rapid detection of drug-resistant TB. LPAs offer short turn-around times (as little as 1-3 days) between sample collection and delivery of test results. The PROVE IT LPA study will test the performance of LPAs within different health systems through field evaluation studies conducted in Brazil, Russia, and South Africa. The goals of the studies are to identify the number of additional cases of drug resistant TB discovered through the use of LPA technology as opposed to older techniques, to assess how diagnosis through the use of LPAs leads to patients being placed on appropriate treatment, to determine how LPAs affect the transmission of drug resistant TB, what types of patients benefit most from the introduction of LPA technology, and what laboratory measures are needed to optimize the use of LPAs in various settings. Results of these studies should help to inform the integration of LPA technology into the health systems within high burden countries. Research period: 2010-2012
The TREAT TB Modelling Collaboration for New Diagnostic ToolsThe TREAT TB modeling collaboration for new diagnostic tools is a component of the TREAT TB Diagnostic Tools Initiative. Several technical partners are collaborating to create a comprehensive modeling approach that offers improved guidance to managers and policy‐makers in high‐burden countries regarding the packages of diagnostic tools most suitable for their epidemiological settings as well as the health system requirements associated with the adoption and implementation of these tools on a large scale. This is innovative approach will address both traditional transmission modeling as well as health systems modeling. Transmission modeling projects the potential impact of new tools on the transmission of TB within a population using key information obtained from field evaluation and operational research, such as: the “on‐the‐ground” operational characteristics of the tests (e.g. sensitivity and specificity); estimates of the reduction in time to treatment initiation; and estimated reduction in number of patients lost to follow up during the diagnostic process. Health systems modeling evaluates the potential impact of new tools on the functioning of health systems through the analysis of key operational questions such as: what are the professional and human resources requirements, what are the costs associated with the introduction and scale‐up of new tools, and what are the key system bottlenecks in going to scale with new diagnostic tools and packages. As new diagnostic tools continue to emerge at a fast pace and international recommendations are modified as a result, this combined approach to diagnostic modeling is much needed to give national level decision makers the information necessary to make important decisions related to the adoption of diagnostic tools and packages. TREAT TB-sponsored Systematic ReviewsSystematic reviews focus on summarizing large bodies of evidence and help to explain differences among studies on the same question. Reviews involve the application of scientific strategies, in ways that limit bias, and the assembly, appraisal, and synthesis of all relevant studies that address a specific clinical or public health question. A meta-analysis is a type of systematic review that uses statistical methods to combine and summarize the results of several primary studies. Under the TREAT TB Diagnostic Tools Initiative, The Union and its partners engage closely with technical experts, working groups, and scientific advisory committees on a continuous basis in order to identify specific needs for systematic reviews on topics related to new and improved diagnostic tools and strategies. TREAT TB-sponsored reviews are led by an expert team from McGill University in collaboration with TREAT TB partners and collaborators. Since the inception of the TREAT TB Initiative, the following systematic reviews have been undertaken:
Use of Microscopic Observation Drug Susceptibility (MODS) Assay or Thin Layer Agar (TLA) Techniques for the Diagnosis of Active Tuberculosis and/or for Drug Sensitivity TestingFor the diagnosis of active TB, smear microscopy is a simple, low-cost technique, which can be implemented in health facilities with minimum infrastructure in resource-limited settings. However, smear microscopy is labor intensive and has several limitations including low sensitivity in patients with less advanced disease and in HIV-infected patients. Mycobacterial culture through solid media as a diagnostic tool can be produced locally at very low cost, but it is slow, requiring four to eight weeks for results. Liquid culture techniques provide results within two to four weeks in most patients, and are more sensitive than solid media. However, liquid culture is more expensive to operate. The thin layer agar (TLA) method provides results much more rapidly with an average time to detection of 10-14 days. MODS is a variant of TLA which uses liquid medium and detects mycobacterial growth within 7-14 days using an inverted light microscope. Both techniques are simple and low cost requiring minimal equipment, and they can also be used for drug susceptibility testing (DST), which is currently available for a very limited number of patients in low- and middle-income countries. MODS and TLA have been shown to successfully reduce the time from specimen receipt to DST results to less than two weeks. Hence, these are very promising techniques not only for rapid diagnosis of disease but also for rapid diagnosis of drug resistance. The objective of this Systematic Review and meta-analysis is to compare MODS, TLA and reference standards in terms of their sensitivity and specificity for the diagnosis of active TB and the diagnosis of resistance to first line TB drugs, and to examine the time requirements, costs and bio-safety issues for each. Research Period: 2009
Lipoarabinomannan (LAM) Antigen Detection for the Diagnosis of Tuberculosis: a Systematic Review and Meta-AnalysisLAM is a heat-stable glycolipid component of the cell wall of Mycobacterium tuberculosis (MTB). It can be detected in the urine of culture-confirmed TB cases and has been identified as a promising marker of active TB disease. LAM antigen detection has many potential benefits compared to currently used diagnostics. Urine samples are simple to collect, process, and store. The collection process requires minimal patient instruction and there are far fewer infection control concerns when collecting urine compared to sputum for diagnosis. There have now been several evaluations of LAM-based diagnostics and it is important to systematically review the existing evidence base on accuracy of LAM antigen detection for TB. The objective of this Systematic Review is to evaluate the accuracy and performance of urinary LAM-based tests for the diagnosis of active TB. To review and summarize user-important characteristics of urinary LAM-based tests, such as time to result and rate of indeterminate results. Research Period: 2009-2010
Interferon-Gamma Release Assays (IGRAs) for the detection of Mycobacterium tuberculosis (M.tb) infection in children: a systematic review and meta-analysisThere is no gold standard for the detection of M.tb infection. Although routinely used, the tuberculin skin test (TST) has limited sensitivity and specificity. TST limitations place children at risk of both under and over treatment for infection, unnecessarily burdening patients, families and resource-limited health systems, while failing to identify children at the highest risk of progression to TB disease. IGRAs were developed for detection of M.tb infection. A growing number of studies have compared the TST and IGRAs for the detection of M.tb infection in children using a variety of methodological approaches and various populations. Other studies have measured the sensitivity of the test in children with active TB disease, while measuring the specificity in children with a minimal risk of infection. In light of this rapidly growing body of literature, it is important to systematically review the existing evidence base on accuracy of IGRAs for the detection of M.tb infection in children to guide clinical practice in settings with varying TB and HIV disease burden. Research Period: 2010 |
