TY - JOUR
T1 - A Multi-Country Non-Inferiority Cluster Randomized Trial of Frontloaded Smear Microscopy for the Diagnosis of Pulmonary Tuberculosis
AU - Cuevas, Luis
AU - Yassin, Mohammed Ahmed
AU - Al-Sonboli, Najla
AU - Lawson, Lovett
AU - Arbide, Isabel
AU - Al-Aghbari, Nasher
AU - Sherchand, Jeevan Bahadur
AU - Al-Absi, Amin
AU - Emenyonu, Emmanuel Nnamdi
AU - Merid, Yared
AU - Okobi, Mosis Ifenyi
AU - Onuoha, Juliana Olubunmi
AU - Aschalew, Melkamsew
AU - Aseffa, Abraham
AU - Harper, Greg
AU - de Cuevas, Rachel Mary Anderson
AU - Kremer, Kristin
AU - van Soolingen, Dick
AU - Nathanson, Carl Michael
AU - Joly, Jean
AU - Faragher, Brian
AU - Squire, Bertie
AU - Ramsay, Andrew
PY - 2011/7/12
Y1 - 2011/7/12
N2 - BackgroundMore 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.Methods and FindingsThis 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.ConclusionsThe 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.
AB - BackgroundMore 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.Methods and FindingsThis 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.ConclusionsThe 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.
U2 - 10.1371/journal.pmed.1000443
DO - 10.1371/journal.pmed.1000443
M3 - Article
SN - 1549-1277
VL - 8
SP - e1000443
JO - PLoS Medicine
JF - PLoS Medicine
IS - 7
M1 - e1000443
ER -
