December, 2016 - SUPPORT Summary of a systematic review | print this article |

Is directly observed therapy effective for treating tuberculosis?

Successful tuberculosis treatment depends on adherence to treatment schedules, which people often find difficult. Directly observed therapy (DOT) requires a health worker, family or community member to witness the physical drug intake, and has been widely promoted as a means to improve adherence to treatment.

Key messages

  • In treatment of active tuberculosis in the general population

–  DOT probably leads to little or no difference to whether patients are cured, and/or whether they complete treatment

–  DOT delivered at home probably leads to a small increase in cure rates and/or treatment completion compared to self-administration

–  DOT delivered at clinics probably leads to little or no difference in cure rates or treatment completion compared to self-administration

–  DOT delivered at clinics probably leads to little or no difference in cure rates or treatment completion compared to DOT delivered at home

–  DOT delivered at home by a health worker probably leads to little or no increase in cure rates or treatment completion compared to DOT delivered at home by a family member

 

  • In prophylaxis of tuberculosis in intravenous drug users

–   DOT probably leads to little or no difference in treatment completion compared to self-administration

–   DOT at a chosen location probably leads to little or no difference in treatment completion compared to DOT at a treatment centre

Background

Tuberculosis is an infectious disease that continues to be a major public health problem, particularly in low- and middle-income countries. Effective drugs to prevent or cure tuberculosis are available but successful treatment depends on good adherence to treatment schedules. Individuals receiving treatment often find adherence difficult. Directly observed therapy (DOT) requires a health worker, family or community member to witness the physical drug intake in a health centre or in a patient’s home. DOT has been widely promoted as a means to improve adherence to treatment and is at the core of the DOTS programme promoted by the World Health Organization. There is little strong evidence, however, for its effectiveness.

 



About the systematic review underlying this summary

 

    Review objectives: To compare DOT with self-administration of treatment or different DOT options for people requiring treatment for clinically active tuberculosis or prevention of active disease.
    Type of What the review authors searched for What the review authors found
    Study designs & interventions Studies evaluating health workers, family members, or community volunteers routinely observing participants taking anti-tuberculosis drugs

    11 randomised trials and quasi-randomised trials with a combined total of 5,609 participants

     


    Participants People requiring treatment for clinically active tuberculosis or medication for preventing active disease (prophylaxis or preventive therapy)
    9 studies on the general population (treatment of active tuberculosis) with a combined total of 5,302 participants and 2 studies on intravenous drug users (prophylaxis) with a combined total of 307 participants
    Settings No restrictions

    8 studies set in low- and middle-income countries: Pakistan (1), South Africa (2), Tanzania (2), Nepal (1), Swaziland (1), Thailand (1)

    3 studies set in high-income countries: Australia (1), United States of America (USA) (2 studies including intravenous drug users)


    Outcomes Cure; Completion of treatment; Development of clinical tuberculosis (in trials of drug prophylaxis); Keeping outpatient appointments
    Cure (4 studies), Cure or completion of treatment (6), and Completion of treatment (3). Some studies reported multiple outcomes.
    Date of most recent search: August 2007

    Limitations: This is a well-conducted systematic review with only minor limitations.

     Volmink J, Garner P.Directly observed therapy for treating tuberculosis. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD003343. DOI: 10.1002/14651858.CD003343.pub3

 

Summary of findings

The review identified 11 trials, including 9 on the delivery of anti-tuberculosis treatment to members of the general population, and 2 on prophylactic treatment of intravenous drug users. Eight studies were conducted in low- and middle-income countries; both the studies of intravenous drug users were conducted in the USA. Data on the cure of tuberculosis and completion of treatment were identified; no data were found on the development of clinical tuberculosis and keeping outpatient appointments.

1) Treatment of active tuberculosis – general population

Included studies compared DOT with self-administration and compared alternative DOT delivery options.

 

  • DOT probably leads to little or no difference in cure rates, and/or completion of treatment. The certainty of this evidence is moderate. DOT delivered at home probably leads to a small increase in cure rates and/or treatment completion compared to self‑administration. The certainty of this evidence is moderate.
  • DOT delivered at clinics may lead to a small decrease in cure rates or treatment completion compared to self-administration. The certainty of this evidence is low.
  • DOT delivered at clinics probably leads to little or no increase in cure rates or treatment completion compared to DOT delivered at home. The certainty of this evidence is moderate.
  • DOT delivered at home by a health worker probably leads to little or no increase in cure rates or treatment completion compared to DOT delivered at home by a family member. The certainty of this evidence is moderate.

DOT versus self-administration and DOT in various locations and through different channels

Women's groups practicing participatory learning and action compared to usual care

People:  Women of reproductive age
Settings
:  Rural areas in low- and middle-income countries
Intervention
: Women's groups practicing participatory learning and action
Comparison
: Usual care

Outcome

Absolute effect*

Relative effect (95% CI)

Certainty of the evidence (GRADE)

Without

Women's groups

With

Women's groups

Cure

Self-administration

63

per 100

DOT

64

per 100

RR 1.02

(0.86 to 1.21)

Moderate

Difference: 1 more cured per 100 people receiving TB treatment

(Margin of error: 9 fewer to 13 more)

Self-administration

64

per 100

DOT (at home)

70

per 100

RR 1.10

(1.02 to 1.18)

Moderate

Difference: 6 more cured per 100 people receiving TB treatment

(Margin of error: 1 to 11 more)

Self-administration

56

Per 100

DOT (at clinic)

49

per 100

RR 0.88

(0.72 to 1.06)

Low

Difference: 7 fewer cured per 100 people receiving TB treatment

(Margin of error: 16 fewer to 3 more)

Cure or completion of treatment

Self-administration

71

per 100

DOT

75

per 100

RR 1.06

(1.00 to 1.13)

Moderate

Difference: 4 more cured or completed treatment per 100 people receiving TB treatment

(Margin of error: 0 to 9 more)

Self-administration

72

per 100

DOT (at home)

78

per 100

RR 1.09

(1.02 to 1.16)

Moderate

Difference: 6 more cured or completed treatment per 100 people receiving TB treatment

(Margin of error: 1 to 11 more)

Self-administration

63

per 100

DOT (at clinic)

58

per 100

RR 0.92

(0.78 to 1.08)

Moderate

Difference: 5 fewer cured or completed treatment per 100 people receiving TB treatment

(Margin of error: 14 fewer to 5 more)

DOT (at clinic)

83

per 100

DOT (at home)

85

per 100

RR 1.03

(0.96 to 1.10)

Moderate

Difference: 2 more cured or completed treatment per 100 people receiving TB treatment

(Margin of error: 3 fewer to 8 more)

DOT (at home, health worker)

68

per 100

DOT (at home, family member)

66

per 100

RR 0.97

(0.90 to 1.05)

Moderate

Difference: 2 fewer cured or completed treatment per 100 people receiving TB treatment

(Margin of error: 7 fewer to 4 more)

Completion of treatment

Self-administration

91

per 100

DOT

96

per 100

RR 1.06

(0.98 to 1.15)

Moderate

Difference: 5 more completed treatment per 100 people receiving TB treatment

(Margin of error: 2 fewer to 9 more)

Margin of error = Confidence interval (95% CI) RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page)

* The risk WITHOUT the intervention is based on DOTS or one DOTS option. The corresponding risk WITH the intervention (and the 95% confidence interval for the difference) is based on the overall relative effect (and its 95% confidence interval).

2) Prophylaxis of tuberculosis - intravenous drug users

Included studies compared DOT with self-administration, and compared alternative DOT delivery options.

  • DOT probably leads to little or no increase in treatment completion compared to self‑administration. The certainty of this evidence is moderate.
  • DOT at a location chosen by the patient may lead to slightly lower treatment completion compared to DOT at a treatment centre. The certainty of this evidence is low.
 Women's groups practicing participatory learning and action compared to usual care

People:  Women of reproductive age
Settings
:  Rural areas in low- and middle-income countries
Intervention
: Women's groups practicing participatory learning and action
Comparison
: Usual care

Outcome

Absolute effect*

Relative effect (95% CI)

Certainty of the evidence (GRADE)

Without

Women's groups

With

Women's groups

Completion of treatment

Self-administration

79 

per 100

DOT

81

per 100

RR 1.02

(0.89 to 1.18)

Moderate

Difference: 2 more completed treatment per 100 IVD users receiving TB prophylaxis

(Margin of error: 9 fewer to 14 more)

Treatment centre

60

per 100

Chosen location

53

per 100

RR 0.88

(0.63 to 1.23)

Low

Difference: 7 fewer completed treatment per 100 IVD users receiving TB prophylaxis

(Margin of error: 22 fewer to 14 more)

Margin of error = Confidence interval (95% CI) RR: Risk ratio GRADE: GRADE Working Group grades of evidence (see above and last page)

* The risk WITHOUT the intervention is based on DOTS or one DOTS option. The corresponding risk WITH the intervention (and the 95% confidence interval for the difference) is based on the overall relative effect (and its 95% confidence interval).


Relevance of the review for low-income countries

Findings Interpretation*
APPLICABILITY

 

  • Eight of the 9 studies focusing on the treatment of active tuberculosis among members of the general population were conducted in low- and middle-income countries.
  • The study investigating prophylaxis for intravenous drug users was conducted in the USA.

The findings are of direct relevance to low-income countries.

The heterogeneity between the findings from studies conducted in different country settings suggests as-yet unidentified confounders (for example, local habits and cultural characteristics)

The findings from the two studies that investigated prophylaxis for intravenous drug users may be transferable to low-income country settings but the delivery process and support structures for local population may differ from those of the original study settings


EQUITY
  • The review did not include information on equity.
DOT frequently involves costs (financial, time, productivity) for patients. Self-treatment might avoid these costs, potentially rendering adherence to anti-tuberculosis treatment schedules more feasible in poor populations.
ECONOMIC CONSIDERATIONS
  • The review did not provide data related to economic considerations.
DOT is costly for health services. Available evidence suggests that DOT leads to little or no differences in cure rates or completion of treatment. Compared to other forms of administration, such resources could be invested in interventions of proven effectiveness in order to improve adherence.
MONITORING & EVALUATION
  • The review did not find evidence of the effects of DOT on development of clinical tuberculosis (for those receiving prophylaxis) or on keeping outpatient appointments.

There needs to be a clear identification of the contexts in which DOT is beneficial (e.g. specific health systems and cultural characteristics).

The effects of DOT on the development of clinical tuberculosis (for those receiving prophylaxis) and on keeping outpatient appointments requires further research.


*Judgements made by the authors of this summary, not necessarily those of the review authors, based on the findings of the review and consultation with researchers and policymakers in low-income countries. For additional details about how these judgements were made see:
www.supportsummaries.org/methods



 

Additional information

Related literature

Bayer R, Wilkinson D. Directly observed therapy for tuberculosis: history of an idea. Lancet 1995;345(8964):1545–8.

 

Chaulk CP, Kazandjian VA. Directly observed therapy for treatment completion of pulmonary tuberculosis: Consensus Statement of the Public Health Tuberculosis Guidelines Panel. JAMA 1998;279(12):943–8.

 

Frieden TR, Sbarbaro JA. Promoting adherence to treatment for tuberculosis: the importance of direct observation. Bulletin of the World Health Organization 2007;85(5):407–9.

 

Garner P, Smith H, Munro S, Volmink J. Promoting adherence to tuberculosis treatment. Bulletin of the World Health Organization 2007;85(5):404–9.

 

Volmink J, Matchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet 2000;355(9212):1345–50.

 

Cox HS, Morrow M, Deutschmann PW. Long term efficacy of DOTS regimens for tuberculosis: systematic review. BMJ 2008;336(7642):484-7.

 

Kangovi S, Mukherjee J, Bohmer R, Fitzmaurice G. A classification and meta-analysis of community-based directly observed therapy programs for tuberculosis treatment in developing countries. Journal of Community Health 2009;34(6):506-13.

 

This summary was prepared by

Peter Steinmann, Swiss Tropical and Public Health Institute, Switzerland

 

Conflict of interest

None declared. For details, see: www.supportsummaries.org/coi

 

Acknowledgements

This summary has been peer reviewed by: Gabriel Rada, Paul Garner, Simon Goudie, and Hanna Bergman.

 

This review should be cited as

Volmink J, Garner P. Directly observed therapy for treating tuberculosis. Cochrane Database of Systematic
Reviews
2007, Issue 4. Art. No.: CD003343. DOI: 10.1002/14651858.CD003343.pub3.

 

The summary should be cited as

Steinmann P. Is directly observed therapy effective for treating tuberculosis? A SUPPORT Summary of a systematic review. December 2016. www.supportsummaries.org

 

Keywords

 

evidence-informed health policy, evidence-based, systematic review, health systems research, health care, low and middle-income countries, developing countries, primary health care, tuberculosis, compliance, treatment, directly observed therapy, DOT



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