Directly observed therapy for treating tuberculosis

Abstract

Background: Tuberculosis (TB) requires at least six months of treatment. If treatment is incomplete, patients may not be cured and drug resistance may develop. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence by requiring health workers, community volunteers or family members to observe and record patients taking each dose.

Objectives: To evaluate DOT compared to self-administered therapy in people on treatment for active TB or on prophylaxis to prevent active disease. We also compared the effects of different forms of DOT.

Search methods: We searched the following databases up to 13 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS and mRCT. We also checked article reference lists and contacted relevant researchers and organizations.

Selection criteria: Randomized controlled trials (RCTs) and quasi-RCTs comparing DOT with routine self-administration of treatment or prophylaxis at home.

Data collection and analysis: Two review authors independently assessed risk of bias of each included trial and extracted data. We compared interventions using risk ratios (RR) with 95% confidence intervals (CI). We used a random-effects model if meta-analysis was appropriate but heterogeneity present (I(2) statistic > 50%). We assessed the quality of the evidence using the GRADE approach.

Main results: Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self-administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self-administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self-administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence). In a subgroup analysis stratified by the frequency of contact between health services in the self-treatment arm, daily DOT may improve TB cure when compared to self-administered treatment where patients in the self-administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two weeks: RR 0.96, 95% CI 0.83 to 1.12; one trial, 497 participants; every week: RR 0.90, 95% CI 0.68 to 1.21; two trials, 248 participants).Treatment completion showed a similar pattern, ranging from 59% to 78% in the self-treatment groups, and direct observation did not improve this (RR 1.07, 95% CI 0.96 to 1.19; six trials, 1839 participants, moderate quality evidence). DOT at home versus DOT at health facility In four trials that compared DOT at home by family members, or community health workers, with DOT by health workers at a health facility there was little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.88 to 1.18, four trials, 1556 participants, moderate quality evidence; treatment completion: RR 1.04, 95% CI 0.91 to 1.17, three trials, 1029 participants, moderate quality evidence). DOT by family member versus DOT by community health workerTwo trials compared DOT at home by family members with DOT at home by community health workers. There was also little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.86 to 1.21; two trials, 1493 participants, moderate quality evidence; completion: RR 1.05, 95% CI 0.90 to 1.22; two trials, 1493 participants, low quality evidence). Specific patient categoriesA trial of 300 intravenous drug users in the USA evaluated direct observation with no observation in TB prophylaxis to prevent active disease and showed little difference in treatment completion (RR 1.00, 95% CI 0.88 to 1.13; one trial, 300 participants, low quality evidence).

Authors' conclusions: From the existing trials, DOT did not provide a solution to poor adherence in TB treatment. Given the large resource and cost implications of DOT, policy makers might want to reconsider strategies that depend on direct observation. Other options might take into account financial and logistical barriers to care; approaches that motivate patients and staff; and defaulter follow-up.

Conflict of interest statement

As a result of the earlier editions of this review from the mid 1990s, PG has become recognised and associated with the continued debate about whether DOT should be central to national programmes in low‐ and middle‐income countries.

Figures

1

Factors influencing adherence and possible intervention points.

2

Risk of bias summary: review authors' judgements about each risk of bias item for each included trial.

3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included trials.

1.1. Analysis

Comparison 1 Directly observed versus self‐administered, Outcome 1 Cure (negative sputum smear in last month of Rx in patients +ve initially).

1.2. Analysis

Comparison 1 Directly observed versus self‐administered, Outcome 2 Cure (by intensity of monitoring in control group).

1.3. Analysis

Comparison 1 Directly observed versus self‐administered, Outcome 3 Treatment completion (both with smear sputum test at end and those without).

1.4. Analysis

Comparison 1 Directly observed versus self‐administered, Outcome 4 Treatment completion (grouped by frequency of monitoring in the self‐administered therapy group).

2.1. Analysis

Comparison 2 Home observed versus clinic observed, Outcome 1 Cure (having a negative sputum smear test in the last month of treatment having been smear‐positive initially).

2.2. Analysis

Comparison 2 Home observed versus clinic observed, Outcome 2 Treatment completion (both with smear sputum test at end and those without).

2.3. Analysis

Comparison 2 Home observed versus clinic observed, Outcome 3 Cure (stratified by intensity of observation).

3.1. Analysis

Comparison 3 Community observed vs family observed, Outcome 1 Cure (having a negative sputum smear test in the last month of treatment having been smear‐positive initially).

3.2. Analysis

Comparison 3 Community observed vs family observed, Outcome 2 Treatment completion (both with smear sputum test at end and those without).

4.1. Analysis

Comparison 4 Injecting drug users, Outcome 1 Treatment completion.

References

References to studies included in this review Chaisson 2001 USA {published data only}

Hsieh 2008 TWN {published data only} Kamolratanakul 1999 THA {published data only} Lwilla 2003 TZA {published data only} MacIntyre 2003 AUS {published data only} Newell 2006 NPL {published data only} Walley 2001 PAK {published data only} Wandwalo 2004 TZA {published data only} Wright 2004 SWZ {published data only} Zwarenstein 1998 ZAF {published data only} Zwarenstein 2000 ZAF {published data only} References to studies excluded from this review Batki 2002 {published data only} Carroll 2004 {published data only} Hwang 2004 {published data only} Jasmer 2004 {published data only} Lewin 2004 {published data only} Malotte 2001 {published data only} Matthew 2002 {published data only} Moulding 2002 {published data only} Pungrassami 2002a {published data only} Pungrassami 2002b {published data only} Sorete‐Abore 2002 {published data only} Tandon 2002 {published data only} Thiam 2007 {published data only} Toyota 2003 {published data only} Additional references Anuwatnonthakate 2008 Barbara 2013 Bayer 1995 Bosch‐Capblanch 2007 Chan 2002 Chaulk 1998 Chien 2013 Dick 2005 Ford 2009 Frieden 2003 Frieden 2007 Gross 2009 Higgins 2011 Hirpa 2013 Hopewell 2006 Jüni 2001 Khan 2003 Liu 2008 Lutge 2012 M'Imunya 2012 Macq 2003 Mohan 2007 Moonan 2011 Munro 2007 Pasipanodya 2013 Review Manager 5 [Computer program] Sepkowitz 1995 Smieja 2010 Steffen 2010 Tian 2014 van den Boogaard 2012 Volmink 2000b WHO 2002 WHO 2010 WHO 2013 References to other published versions of this review Volmink 1997 Volmink 2000a Volmink 2001 Volmink 2003 Volmink 2006 Volmink 2007