A meta-analysis of self-administered vs directly observed therapy effect on microbiologic failure, relapse, and acquired drug resistance in tuberculosis patients

Abstract

Background: Preclinical studies and Monte Carlo simulations have suggested that there is a relatively limited role of adherence in acquired drug resistance (ADR) and that very high levels of nonadherence are needed for therapy failure. We evaluated the superiority of directly observed therapy (DOT) for tuberculosis patients vs self-administered therapy (SAT) in decreasing ADR, microbiologic failure, and relapse in meta-analyses.

Methods: Prospective studies performed between 1965 and 2012 in which adult patients with microbiologically proven pulmonary Mycobacterium tuberculosis were separately assigned to either DOT or SAT as part of short-course chemotherapy were chosen. Endpoints were microbiologic failure, relapse, and ADR in patients on either DOT or SAT.

Results: Ten studies, 5 randomized and 5 observational, met selection criteria: 8774 patients were allocated to DOT and 3708 were allocated to SAT. For DOT vs SAT, the pooled risk difference for microbiologic failure was .0 (95% confidence interval [CI], -.01 to .01), for relapse .01 (95% CI, -.03 to .06), and for ADR 0.0 (95% CI, -0.01 to 0.01). The incidence rates for DOT vs SAT were 1.5% (95% CI, 1.3%-1.8%) vs 1.7% (95% CI, 1.2%-2.2%) for microbiologic failure, 3.7% (95% CI, 0.7%-17.6%) vs 2.3% (95% CI, 0.7%-7.2%) for relapse, and 1.5% (95% CI, 0.2%-9.90%) vs 0.9% (95% CI, 0.4%-2.3%) for ADR, respectively. There was no evidence of publication bias.

Conclusions: DOT was not significantly better than SAT in preventing microbiologic failure, relapse, or ADR, in evidence-based medicine. Resources should be shifted to identify other causes of poor microbiologic outcomes.

Keywords: acquired drug resistance; directly observed therapy; microbiologic failure; self-administered therapy; tuberculosis.

Figure 1.

Summary of literature search and study selection for the meta-analysis. Abbreviations: DOT, directly observed therapy; HIV, human immunodeficiency virus; SAT, self-administered therapy; TB, tuberculosis.

Figure 2.

Pooled risk differences for defaulting in patients on directly observed therapy compared to self-administered therapy. Abbreviations: CI, confidence interval; DOT, directly observed therapy; ID, identity; RD, risk difference; SAT, self-administered therapy.

Figure 3.

Pooled risk differences for microbiologic failure in patients on directly observed therapy compared to self-administered therapy. Abbreviations: CI, confidence interval; DOT, directly observed therapy; ID, identity; RD, risk difference; SAT, self-administered therapy.

Figure 4.

Publication bias analysis and small study effects for microbiologic failure. Abbreviation: RD, risk difference.

Figure 5.

Pooled risk difference for relapse on directly observed therapy compared to self-administered therapy. Abbreviations: CI, confidence interval; DOT, directly observed therapy; ID, identity; RD, risk difference; SAT, self-administered therapy.

Figure 6.

Publication bias analysis and small study effects for relapse. Abbreviation: RD, risk difference.

Figure 7.

Effect of directly observed therapy vs self-administered therapy on acquired drug resistance. Abbreviations: CI, confidence interval; DOT, directly observed therapy; ID, identity; RD, risk difference; SAT, self-administered therapy.