A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis


Cuevas, Luis Eduardo ORCID: 0000-0002-6581-0587, Yassin, Mohammed Ahmed, Al-Sonboli, Najla, Lawson, Lovett, Arbide, Isabel, Al-Aghbari, Nasher, Sherchand, Jeevan Bahadur, Al-Absi, Amin, Emenyonu, Emmanuel Nnamdi, Merid, Yared et al (show 13 more authors) (2011) A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis. PLOS MEDICINE, 8 (7). e1000443-.

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Abstract

<h4>Background</h4>More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out.<h4>Methods and findings</h4>This clinical trial of adults with cough ≥2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected "on the spot" during the first visit plus one sputum sample collected the following morning (spot-spot-morning [SSM]) versus the standard spot-morning-spot (SMS) scheme. Analyses were per protocol analysis (PPA) and intention to treat (ITT). A sub-analysis compared just the first two smears of each scheme, spot-spot and spot-morning. In total, 6,627 patients (3,052 SSM/3,575 SMS) were enrolled; 6,466 had culture and 1,526 were culture-positive. The sensitivity of SSM (ITT, 70.2%, 95% CI 66.5%-73.9%) was non-inferior to the sensitivity of SMS (PPA, 65.9%, 95% CI 62.3%-69.5%). Similarly, the specificity of SSM (ITT, 96.9%, 95% CI 93.2%-99.9%) was non-inferior to the specificity of SMS (ITT, 97.6%, 95% CI 94.0%-99.9%). The sensitivity of spot-spot (ITT, 63.6%, 95% CI 59.7%-67.5%) was also non-inferior to spot-morning (ITT, 64.8%, 95% CI 61.3%-68.3%), as the difference was within the selected -5% non-inferiority limit (difference ITT = 1.4%, 95% CI -3.7% to 6.6%). Patients screened using the SSM scheme were more likely to provide the first two specimens than patients screened with the SMS scheme (98% versus 94.2%, p<0.01). The PPA and ITT analysis resulted in similar results.<h4>Conclusions</h4>The sensitivity and specificity of SSM are non-inferior to those of SMS, with a higher proportion of patients submitting specimens. The scheme identifies most smear-positive patients on the first day of consultation.<h4>Trial registration</h4>Current Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.

Item Type: Article
Uncontrolled Keywords: Sputum, Humans, Mycobacterium tuberculosis, Tuberculosis, Pulmonary, Cough, Microscopy, Mass Screening, Specimen Handling, Cluster Analysis, Sensitivity and Specificity, Patient Compliance, Adult, Middle Aged, Female, Male, Young Adult, Intention to Treat Analysis
Depositing User: Symplectic Admin
Date Deposited: 31 May 2016 08:11
Last Modified: 13 Feb 2023 17:58
DOI: 10.1371/journal.pmed.1000443
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3001411
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