Impact of a novel molecular TB diagnostic system in patients at high risk of TB mortality in rural South Africa (Uchwepheshe): Study protocol for a cluster randomised trial

Trials (Impact Factor: 1.73). 06/2013; 14(1):170. DOI: 10.1186/1745-6215-14-170
Source: PubMed


Tuberculosis control in sub-Saharan Africa has long been hampered by poor diagnostics and weak health systems. New molecular diagnostics, such as the Xpert® MTB/RIF assay, have the potential to improve patient outcomes. We present a cluster randomised trial designed to evaluate whether the positioning of this diagnostic system within the health system has an impact on important patient-level outcomes.

This pragmatic cluster randomised clinical trial compared two positioning strategies for the Xpert MTB/RIF system: centralised laboratory versus primary health care clinic. The cluster (unit of randomisation) is a 2-week time block at the trial clinic. Adult pulmonary tuberculosis suspects with confirmed human immunodeficiency virus infection and/or at high risk of multidrug-resistant tuberculosis are enrolled from the primary health care clinic. The primary outcome measure is the proportion of culture-confirmed pulmonary tuberculosis cases initiated on appropriate treatment within 30 days of initial clinic visit. Univariate logistic regression will be performed as the primary analysis using generalised estimating equations with a binomial distribution function and a logit link.

Diagnostic research tends to focus only on performance of diagnostic tests rather than on patient-important outcomes. This trial has been designed to improve the quality of evidence around diagnostic strategies and to inform the scale-up of new tuberculosis diagnostics within public health systems in high-burden settings.

Trial registration
Current Controlled Trials ISRCTN18642314; South African National Clinical Trials Registry DOH-27-0711-3568.

Download full-text


Available from: Richard Lessells, Oct 13, 2015
29 Reads
  • Source
    • "Several studies included in this review compared outcomes before and after the introduction of PoC CD4, and the observed changes may have been due to other programme improvements during the reporting period. Diagnostic research tends to focus on test performance rather than patient related outcomes [29] although efforts are underway to carry out high quality studies to address these questions in other disease areas [30] and similar studies would be helpful for PoC diagnostics. Inconsistency in outcome reporting meant that each outcome was assessed by only a subset of studies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Point-of-care testing for CD4 cell count is considered a promising way of reducing the time to eligibility assessment for antiretroviral therapy (ART) and of increasing retention in care prior to treatment initiation. In this review, we assess the available evidence on the patient and programme impact of point-of-care CD4 testing. Methods We searched nine databases and two conference sites (up until 26 October 2013) for studies reporting patient and programme outcomes following the introduction of point-of-care CD4 testing. Where appropriate, results were pooled using random-effects methods. Results Fifteen studies, mainly from sub-Saharan Africa, were included for review, providing evidence for adults, adolescents, children and pregnant women. Compared to conventional laboratory-based testing, point-of-care CD4 testing increased the likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5–4.9, n=2] and receiving a CD4 result (OR 2.8, 95% CI 1.5–5.6, n=6). Time to being tested was significantly reduced, by a median of nine days; time from CD4 testing to receiving the result was reduced by as much as 17 days. Evidence for increased treatment initiation was mixed. Discussion The results of this review suggest that point-of-care CD4 testing can increase retention in care prior to starting treatment and can also reduce time to eligibility assessment, which may result in more eligible patients being initiated on ART.
    Journal of the International AIDS Society 01/2014; 17(1):18809. DOI:10.7448/IAS.17.1.18809 · 5.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert® MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research.
    The International Journal of Tuberculosis and Lung Disease 09/2014; 18(9):1012-8. DOI:10.5588/ijtld.13.0851 · 2.32 Impact Factor