Date Published: October 29, 2018
Publisher: Public Library of Science
Author(s): Karuna D. Sagili, Malaisamy Muniyandi, Kayzad Soli Nilgiriwala, Kalpita S. Shringarpure, Srinath Satyanarayana, Richard Kirubakaran, Sarabjit S. Chadha, Prathap Tharyan, Vishnu Chaturvedi.
Early and accurate diagnosis of tuberculosis is a priority for TB programs globally to initiate treatment early and improve treatment outcomes. Currently, Ziehl–Neelsen (ZN) stain-based microscopy, GeneXpert and Light Emitting Diode-Fluorescence Microscopy (LED-FM) are used for diagnosing pulmonary drug sensitive tuberculosis. Published evidence synthesising the cost-effectiveness of these diagnostic tools is scarce.
PubMed, EMBASE and Cost-effectiveness analysis registry were searched for studies that reported on the cost-effectiveness of GeneXpert and LED-FM, compared to ZN microscopy for diagnosing pulmonary TB. Risk of bias was assessed independently by four authors using the Consensus Health Economic Criteria (CHEC) extended checklist. The data variables included the study settings, population, type of intervention, type of comparator, year of study, duration of study, type of study design, costs for the test and the comparator and effectiveness indicators. Incremental cost-effectiveness ratio (ICER) was used for assessing the relative cost-effectiveness in this review.
Of the 496 studies identified by the search, thirteen studies were included after removing duplicates and studies that did not fulfil inclusion criteria. Four studies compared LED-FM with ZN and nine studies compared GeneXpert with ZN. Three studies used patient cohorts and eight were modelling studies with hypothetical cohorts used to evaluate cost-effectiveness. All these studies were conducted from a health system perspective, with four studies utilising cost utility analysis. There were considerable variations in costing parameters and effectiveness indicators that precluded meta-analysis. The key findings from the included studies suggest that LED-FM and GeneXpert may be cost effective for pulmonary TB diagnosis from a health system perspective.
Our review identifies a consistent trend of the cost effectiveness of LED-FM and GeneXpert for pulmonary TB diagnosis in different countries with diverse context of socio-economic condition, HIV burden and geographical distribution. However, all the studies used different parameters to estimate the impact of these tools and this underscores the need for improving the methodological issues related to the conduct and reporting of cost-effectiveness studies.
Tuberculosis (TB) remains a leading cause of death worldwide. Globally, 10.4 million new cases were reported by WHO in 2016 . India is amongst the six countries that accounted for 60% of the new cases. The Sustainable Development Goals (SDGs) and the End TB Strategy aim to end the global TB epidemic and reduce TB deaths by 90% and TB incidence by 80% in 2030 . Though TB treatment averted 49 million deaths globally between 2000 and 2015, diagnostic gaps persist . The WHO 2015 report estimates that about 37% of the cases were undiagnosed or not reported . The potential transmission through people with undiagnosed TB to their contacts poses a serious public health problem. Hence, early and accurate diagnosis of TB is now the top priority of national TB programs globally. Delayed diagnosis contributes to continued transmission, poor health outcomes and distress to the patient and the family . Early diagnosis is expected to lead to early treatment initiation and hence better outcomes. Improved diagnostic tools may facilitate early diagnosis and reduce the direct costs of the diagnostic burden on patients and family [5,6]. Currently, Ziehl–Neelsen (ZN) stain-based microscopy, GeneXpert and Light Emitting Diode-Fluorescence Microscopy (LED-FM) are widely used diagnostic tools for drug-sensitive pulmonary tuberculosis by National TB programmes in high burden countries.
This systematic review was conducted following the PRISMA guidelines  (S1 Table). The review protocol is registered at the Prospero registry (Registration No. CRD42016043333) . The objective was to compare the incremental cost-effectiveness of GeneXpert and LED-FM with ZN smear microscopy in the diagnosis of smear-positive pulmonary TB. Though we had initially planned to include Chest X-ray as one of the diagnostic tests evaluated, we excluded it for this review due to the lack of studies providing data comparing cost-effectiveness of Chest X-ray with ZN smear microscopy. Below is the PICO question for this review:
To the best of our knowledge, this is the first systematic review to synthesize the evidence of cost-effectiveness of LED-FM and GeneXpert in comparison to ZN microscopy for pulmonary TB diagnosis. The review also appraised the reporting quality of the published evidence. The key findings from the included studies suggest that the new diagnostic tools LED-FM and GeneXpert are very cost effective for pulmonary TB diagnosis from a health system perspective, even though they are not cost saving to the health system. The evidence from 11 countries, with majority of them having high TB burden shows that these new tools are cost effective irrespective of their economic condition, HIV burden and geographical distribution.
Our review identifies a consistent trend of the cost effectiveness of LED-FM and GeneXpert in different countries with diverse context of socio-economic condition, HIV burden and geographical distribution. However, all the studies used different parameters to estimate the impact of these tools and this underscores the need for improving the methodological issues related to the conduct and reporting of cost-effectiveness studies.