Research Article: An attempt to reproduce a previous meta-analysis and a new analysis regarding the impact of directly observed therapy on tuberculosis treatment outcomes

Date Published: May 23, 2019

Publisher: Public Library of Science

Author(s): Brian McKay, Maria Castellanos, Mark Ebell, Christopher C. Whalen, Andreas Handel, Raffaele Serra.


Directly observed therapy (DOT) is almost universally used for the treatment of TB. Several meta-analyses using different methods have assessed the effectiveness of DOT compared to self-administered therapy (SAT). The results of these meta-analyses often conflict with some concluding DOT is superior and others that there is little or no difference. Meta-analyses can guide policymaking, but such analyses must be reliable. To assess the validity of a previous meta-analysis, we tried to reproduce it. We encountered problems with the previous analysis that did not allow for a meaningful reproduction. We describe the issues we encountered here. We then performed a new meta-analysis comparing the treatment outcomes of adults given treatment with SAT versus DOT. Outcomes in the new analysis are loss to follow-up, treatment failure, cure, treatment completed, and all-cause mortality. All data, documentation, and code used to generate our results is provided. Our new analysis included four randomized and three observational studies with 1603 and 1626 individuals respectively. The pooled relative risks (RR) are as follows: Lost to follow-up (RR = 1.2, 95% CI 0.9, 1.7), Treatment Failure (RR = 1.1, 95% CI 0.6, 2), Cure (RR = 0.9, 95% CI 0.8, 1.1), Treatment Completion (RR = 1, 95% CI 0.9, 1.1), Mortality (RR = 0.9, 95% CI 0.6, 1.3). Based on data from our new meta-analysis, the magnitude of the difference between DOT and SAT for all reported outcomes is small, and none of the differences are statistically significant.

Partial Text

Directly observed therapy (DOT) for the treatment of tuberculosis (TB) is a component of the World Health Organization’s (WHO) recommended DOTS program. While the DOTS program has been successful in reducing tuberculosis incidence, the average annual decrease is far short of the needed reduction to meet the goals of the WHO End TB strategy [1]. DOT requires patients with TB to be observed by another individual while taking their medicine. Evidence to support DOT’s effect on cure rates [2,3], adherence [2,3], or any other measure of treatment success is not very compelling [4,5]. Leading to an intense debate about the use and effectiveness of DOT [6–9].

History has demonstrated that TB control is required to protect public health [50], but the DOT component of TB control has been more controversial. There are a number of meta-analyses that have been published, and the methodology used for the systematic search of the literature appears to impact the results. Specifically, the types of study designs included seems to determine if the findings are statistically significant or not. Studies that include retrospective studies favor DOT and show a statistically significant difference when comparing DOT and SAT [10,51,52].

Documentation and data for reproducibility are freely available in the supplementary materials.