Characteristics of included studies [ordered by study ID]
|
| Methods | Generation of allocation sequence: randomized, with factorial overlay; computer-generated random numbers
Allocation concealment: not stated
Blinding: none
Completeness of follow up: 88% |
|
| | Participants | Number: 300 randomized; 73% men; 85% unemployed; 27% with documented human immunodeficiency virus (HIV) infection
Included: adult, intravenous drug users with positive tuberculin skin test (at least 10 mm induration or 5 mm if HIV positive); given isoniazid preventive therapy for 6 months
Excluded: people with active tuberculosis |
|
| | Interventions | 1. Directly observed therapy (DOT) twice weekly by outreach nurse at clinic or community location
2. Daily self administration of treatment, monthly peer counselling group meetings with lunch, and clinical assessments by a nurse; peer counsellor was a former injection user who had completed preventive therapy, and who was trained in counselling and supervised by a health educator
3. Daily self administration of treatment with monthly clinic assessment; factorial design with immediate or deferred US$10 stipend at the end of each month; deferred payments credited each month and given when treatment completed or participant withdrew |
|
| | Outcomes | 1. 6 months treatment completed, defined as 80% or more of treatments taken (observed for DOT group and 6 monthly visits plus reporting that at least 80% medication taken during a month for other groups)
2. Pill counts
3. Isoniazid metabolites in the urine
4. Electronically monitored bottle opening in a subset |
|
| | Notes | Location: Baltimore City Health Department TB Clinic, USA
Date: 1995-7
Duration of DOT duration not stated |
|
|
|
| Methods | Generation of allocation sequence: central block random allocation scheme prepared for each of 15 study sites; random-number table used
Allocation concealment: none
Blinding: no blinding of assessors
Completeness of follow up: 100% (no losses) |
|
| | Participants | Number: 837 randomized; 73% male
Included: new smear positive adults (aged 15+) |
|
| | Interventions | 1. Daily supervision: participants chose their supervisor from (a) health centre staff, (b) community members, or (c) family members; for (b) and (c) health workers visited homes twice monthly (first 2 months) or monthly for checking of treatment cards, pill counts, and urine tests
2. Self administration of treatment: 1 month drug supply given at diagnosis and after each follow-up visit; no treatment supervision between visits
All participants received the same drug regimen: isoniazid-rifampicin-pyrazinamide-ethambutol for 2 months and isoniazid-rifampicin for 4 months |
|
| | Outcomes | 1. Cure rate (primary outcome): completed 6 months antituberculous therapy, with 2 negative sputum exams, 1 at end of treatment
2. Treatment completion: completed 6 months antituberculous therapy but less than 2 sputum exams
3. Sputum conversion rate: negative sputum at end of third month
4. Percentage defaults
5. Percentage transfers
6. Caseholding rate |
|
| | Notes | Location: Thailand
Date: 1996-7
Duration of
Directly observed therapy (DOT) not stated
Informed consent not obtained as participants were not told that they were participating in a study
Choice of supervisor for DOT participants: 352 chose a family member; 34 chose a community member; and 24 chose health centre staff
One participant in daily supervision arm excluded due to protocol violation so not strictly intention-to-treat |
|
|
|
| Methods | Cluster-randomized controlled trial: 9 pairs of centres matched by type and size
Generation of allocation sequence: unclear
Allocation concealment: unclear
Blinding: none
Completeness of follow up: 87% at 2 months and 69% at 7 months |
|
| | Participants | Number: 18 clusters randomized; 522 participants; mean age 35; 60% male
Included: new smear positive adults |
|
| | Interventions | 1. Community-based directly observed therapy (DOT): daily observation by community health volunteer (site not stated) for intensive 2-month treatment period; health worker visited volunteer every 2 weeks and district co-ordinator visited volunteer monthly; at each visit participants' treatment card checked and drugs counted
2. Institution-based DOT: required to attend health facility daily for 2 months, and then monthly after this
Continuation phase of 6 months: both groups managed the same and expected to self administer treatment daily |
|
| | Outcomes | 1. Sputum negative at 2 months (primary outcome)
2. Cure at 7 months (sputum negative at 2 months and at 5 to 7 months) |
|
| | Notes | Location: Tanzania
Date: 1999-2000
Duration of DOT not stated |
|
|
|
| Methods | Quasi-randomized controlled trial
Generation of allocation sequence: alternate allocation
Concealment of allocation: none
Blinding: assessment of urinary isoniazid blinded
Completeness of follow up: not stated |
|
| | Participants | Number: 173 recruited, mostly foreign nationals; male 51%; mean age 41 (range 14 to 83)
Included: new tuberculosis participants
Excluded: multiple-drug resistant tuberculosis; relapsed tuberculosis; human immunodeficiency virus (HIV)-positive cases; and nontuberculous mycobacterial infections |
|
| | Interventions | 1. Family-based directly observed therapy (DOT): daily observation by a nominated family member who received education and was expected to record participant compliance with pill taking; weekly phone calls from a nurse; nurse on call; nurse home visit every 2 weeks
2. Self administration of treatment: daily
Both groups had monthly visits to health facilities and standardized recording charts |
|
| | Outcomes | Treatment completion measured by:
1. Percentage clinic attendances to collect drugs
2. Urinary isoniazid (6 random checks over months; all had to be > 0) |
|
| | Notes | Location: Australia
Date: 1998 to December 2000
Duration of DOT not stated |
|
|
|
| Methods | Generation of allocation sequence: randomized, blocks of 18
Allocation concealment: sequentially numbered, opaque, sealed envelopes
Blinding: none
Completeness of follow up: not stated |
|
| | Participants | Number: 163 randomized; 82% male
Included: active or recent injection or crack cocaine users screened for tuberculosis with positive tuberculin skin test (at least 10 mm induration or 5 mm if human immunodeficiency virus (HIV)-positive)
Excluded: people with active tuberculosis |
|
| | Interventions | 1. Directly observed therapy (DOT) by outreach worker (location decided by participant) plus US$5 at each visit
2. As (1) but no money
3. DOT at study community site plus US$5
All participants received isoniazid 2 times a week for 6 months or 1 year (depending on HIV status) |
|
| | Outcomes | 1. Percentage medication taken on time; excludes medication taken late (next day)
2. Completion of medication |
|
| | Notes | Location: Long Beach, California, USA
Date: 1994-7
Lost to follow up included prison or moved and were included in outcome (1) but excluded completely from outcome (2) |
|
|
|
| Methods | Cluster-randomized controlled trial
Generation of allocation sequence: 5 randomly selected districts allocated to each arm; the name of each district was written on an individual paper and randomly drawn from a basket
Allocation concealment: method not stated
Blinding: laboratory technicians assessing the primary outcomes were blinded
Completeness of follow up: 100% (no clusters or individuals lost) |
|
| | Participants | Number: 10 districts with 907 people randomized; all smear positive; 67% male
Included: people with tuberculosis (aged 15+); new smear-positive cases, diagnosed at health facilities in the study area; human immunodeficiency virus (HIV) status not known |
|
| | Interventions | 1. Community-based directly observed therapy (DOT): daily treatment supervised by a female community health worker (unpaid volunteer selected by the district health authority) or village health worker (community worker paid by government). Patients mainly visited at home, but occasionally patients met their supervisor at her home. Supervision was for the duration of treatment with drugs provided to the supervisor monthly. Tracing by the supervisor was undertaken for patients who discontinued treatment
2. Family-based DOT: daily supervision by a household member chosen by the participant with drugs provided to the supervisory weekly. Government workers traced those who discontinued treatment |
|
| | Outcomes | 1. Treatment success: cure plus treatment completion [primary]
2. Treatment success compared with the World Health Organization target of 85%
3. Estimated case detection rate with the World Health Organization target of 70%
4. Compare the above rates in men and women |
|
| | Notes | Location: hill and mountain districts of Nepal
Date: 2002-3 |
|
|
|
| Methods | Generation of allocation sequence: computer-generated random numbers
Allocation concealment: opaque, sealed envelopes
Blinding: assessors blinded
Completeness of follow up: not stated |
|
| | Participants | Number: 497 randomized; 51.3% male
Included: adults (aged 15+); new smear-positive cases |
|
| | Interventions | 1. Directly observed therapy (DOT) by a health worker at a health facility that met "access criteria" or a community health worker at or near the participant's home: access criteria were return journey from the participant's home to facility < 2 km, < 2 h duration, and < 10 rupees, and for unmarried women an accompanying relative was available; participants had to attend a health facility or meet a community health worker 6 times per week for 2 months to take their drugs; thereafter they self administered drugs that the participants collected twice a month
2. DOT by a family member chosen by the participant
3. Self administration of drugs collected by participant fortnightly
All participants received isoniazid-rifampicin-pyrazinamide-ethambutol for 2 months and isoniazid-ethambutol for 6 months |
|
| | Outcomes | 1. Cure: sputum negative at 7 or 8 months and on at least 1 previous occasion
2. Treatment completion: treatment completed, but smear results not available on at least 2 occasions before completion of treatment
3. Treatment failure
4. Death
5. Default
6. Transferred out |
|
| | Notes | Location: Pakistan
Date: 1996-8 |
|
|
|
| Methods | Generation of allocation sequence: coin tossing in each of 5 clinics
Allocation concealment: none
Blinding: none
Completeness of follow up: 100% (no losses) |
|
| | Participants | Number: 587 randomized; 322 smear positive, 182 smear negative, and 83 extrapulmonary tuberculosis; 57% male
Included: people with tuberculosis (aged 5+); new smear positive, smear negative, and extrapulmonary cases; human immunodeficiency virus (HIV) status not known
Excluded: previously treated for tuberculosis; severe illness; transferred from another clinic; previously enrolled in the study |
|
| | Interventions | 1. Community-based directly observed therapy (DOT): daily treatment supervised at home by 'guardian' (usually a family member) during 2-month intensive period; supervisors trained to observe drug taking, encourage participants to complete treatment, keep records, collect drugs, and assess drug side effects; during first 2 months participants received 'spot' visits by health workers who conducted treatment card checks and pill counts; during first 2 months participants also requested to attend clinic every 2 weeks for clinical review and progress monitoring
2. Health facility-based DOT: daily supervision at clinic by health workers during the 2 month intensive period
Apart from the observation option participants received the same standardized management including drug therapy |
|
| | Outcomes | 1. Treatment success: cure plus treatment completion
2. Cure: smear positive initially and negative at 7 or 8 months and on at least 1 previous occasion
3. Treatment completion: positive results initially, negative at 2 months and no results at end of treatment; or smear negative initially and received treatment on clinical grounds; or those who completed full course of treatment but had no initial or end-of-treatment results
4. Death: from all causes
5. Treatment failure: participants who remained or became smear positive or 5 months or later
6. Default: failed to collect medication for > 2 consecutive months
7. Transferred out: transferred to a clinic in another area |
|
| | Notes | Location: Dar es Salaam, Tanzania
Date: 2001-3 |
|
|
|
| Methods | Generation of allocation sequence: unclear; stratified into adults and children; then, within each group, randomized by type of tuberculosis (sputum positive, sputum negative, extrapulmonary, relapse)
Allocation concealment: unclear; sealed, sequentially numbered envelopes not stated if opaque
Blinding: assessors of sputum results blinded
Completeness of follow up: 98% |
|
| | Participants | Number: 1353 randomized; 55% male; most 15+ years
Included: adults and children with smear positive or negative, extrapulmonary tuberculosis, or relapse of previously treated tuberculosis
Excluded: died before discharge; or too ill to receive outpatient treatment; lived in area without treatment supporter; or referred in after treatment commenced |
|
| | Interventions | 1. Directly observed therapy (DOT) by community health worker: participants visited for observation daily; community health worker trained to provide daily treatment supervision, record adherence on Treatment Support Card, remind participants who did not report for treatment, and notify diagnostic centre about those who defaulted treatment
2. DOT by family member: family member or carer chosen by participant trained to provide daily treatment supervision, record adherence on Treatment Support Card, and remind participants who did not report for treatment; participants also required to visit the community health worker weekly to check side effects and adherence and receive health education; defaulters reported to the diagnostic centre |
|
| | Outcomes | 1. Cure or treatment completion: cure defined as smear negative at 6 months and on at least 1 previous occasion; treatment completion defined as treatment completed but smear results not available on at least 2 occasions before treatment completion
2. Death
3. Treatment failure: remained or became smear positive at > = 5 months
4. Default: failed to collect medication for > 2 consecutive months
5. Transferred out: formally transferred to another centre |
|
| | Notes | Location: Swaziland
Date: 2000-2 |
|
|
|
| Methods | Generation of allocation sequence: computer-generated random numbers
Allocation concealment: consecutively numbered, opaque, sealed envelopes in each of 5 clinics
Blinding: none
Completeness of follow up: 114/120 (95%) in 1 trial and 102/120 (85%) in other trial excluded from analysis |
|
| | Participants | Number: 216 included in analysis; 62% male; 57% < 35 years
Included: adults (aged 15+) with pulmonary tuberculosis; both new and retreatment cases
Excluded: severe disease or multiple drug resistance; treatment at a non-study clinic for more than 2 weeks; need to be supervised at school or at the workplace; and leaving the area within a month |
|
| | Interventions | 1. Directly observed therapy (DOT) by clinic nurses: participants asked to visit the clinic 5 days a week for 8 weeks (new participants) or for 12 weeks (retreatment participants); thereafter expected attendance was 3 days a week for the continuation phase; clinic visits restricted to normal working hours and adherence card signed and dated by a nurse at each visit and kept at the clinic
2. Self administration of treatment: participants had to visit clinic once a week or send a relative to collect drugs; participants completed their own adherence card for every day of drug taking and a nurse recorded the weekly drug collection; adherence card handed to nurse at the weekly clinic visit
New cases received Rifater (combined rifampicin-isoniazid-pyrazinamide) for 8 weeks followed by Rifinah 4 (combined rifampicin-isoniazid) plus additional isoniazid for 18 weeks
Retreatment participants received Rifater plus ethambutol for 12 weeks and Rifinah plus rifampicin-ethambutol for 22 weeks |
|
| | Outcomes | 1. "Successful treatment" included those who were cured and those who completed treatment; "cured" applied to those who converted from a positive smear and/or culture to a negative smear and/or culture at the end of treatment (6 months for new participants and 8 months for retreatment participants); "treatment completed" referred to participants who (a) completed the full course of treatment but had no pretreatment or post-treatment bacteriological results; (b) had negative pretreatment results and had been treated on clinical grounds; or (c) had positive pretreatment results, negative results after 2 months and no post-treatment results
2. "Treatment failure" applied to participants with a positive smear or culture at the end of treatment
3. "Treatment interrupters" applied to participants who stopped taking treatment for 8 or more weeks during the treatment period
4. Transfer to another treatment facility
5. Death from tuberculosis or other causes while on treatment |
|
| | Notes | Location: 1 trial in each of 2 low-income communities near Cape Town, South Africa
Date: 1994-5
Results combined
54 participants in 1 trial allocated to community supervision not reported in this paper
Exclusions from analysis: trial 1 (6 cases of multiple drug resistance) and trial 2 (12 cases of multiple drug resistance and 6 not tuberculosis)
Number of exclusions per arm of the 2 trials not given |
|
|
|
| Methods | Generation of allocation sequence: computer-generated random numbers
Allocation concealment: consecutively numbered, opaque, sealed envelopes
Blinding: none
Completeness of follow up: not stated |
|
| | Participants | Number: 174 randomized
Included: new or retreatment participants aged 15+ who were sputum or culture positive |
|
| | Interventions | 1. Directly observed therapy (DOT) by clinic nurses (see Zwarenstein 1998)
2. Self administration (see Zwarenstein 1998)
3. DOT by lay health workers: participants took drugs at home of a lay health worker under supervision; if participant missed treatment for 1 day, a lay health worker visited participant's home and if necessary a member of the South African Tuberculosis Association (SANTA) also visited the participant |
|
| | Outcomes | As for Zwarenstein 1998 |
|
| | Notes | Location: 4 clinics in a township near Cape Town, South Africa
Date: 1994-5
18 participants excluded from analysis: 12 with multiple-drug resistant tuberculosis and 6 not tuberculosis |
|
|
Characteristics of excluded studies [ordered by study ID]
|
| Study | Reason for exclusion |
|---|
| | Batki 2001 | Compared direct observation plus with methadone treatment for injecting drug users with routine tuberculosis treatment without methadone |
| | Carroll 2004 | Before-and-after study; no control group |
| | Hwang 2004 | Not randomized |
| | Jasmer 2004 | Different criteria for allocation to self administration or direct observation |
| | Lewin 2004 | An educational intervention was evaluated |
| | Mathew 2002 | Cohort study |
| | Moulding 2001 | Trial evaluating devices that monitor treatment using uranium along a strip of photographic film |
| | Pungrassami 2002 | 2 publications reporting the same study; not randomly allocated |
| | Sorete-Abore 2002 | Cohort study |
| | Tandon 2002 | Described as a randomized trial, but the randomization led to very different numbers in the 2 groups; subsequently over 50 participants (out of a total of 379) crossed over from self treatment to direct observation and were excluded from the analysis; little detail for the rest of the study provided |
| | Thiam 2007 | Multifaceted intervention including directly observed therapy |
| | Toyota 2003 | Patients in hospital |
|
|
Comparison 1. Direct observation versus self administration
Comparison 2. Direct observation versus self administration: stratified by location of direct observation
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Cure | 4 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 3 | 1365 | Risk Ratio (M-H, Fixed, 95% CI) | 1.10 [1.02, 1.18] |
| | | 2 | 444 | Risk Ratio (M-H, Fixed, 95% CI) | 0.88 [0.72, 1.06] |
| | 2 Cure or completion of treatment | 3 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 3 | 1365 | Risk Ratio (M-H, Fixed, 95% CI) | 1.09 [1.02, 1.16] |
| | | 2 | 444 | Risk Ratio (M-H, Fixed, 95% CI) | 0.92 [0.78, 1.08] |
|
|
Comparison 3. Direct observation: home versus clinic
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Cure or completion of treatment | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
|
|
Comparison 4. Home-based direct observation: family member versus community health worker
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Cure or completion of treatment | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
|
|
Comparison 5. Intravenous drug users: direct observation versus self administration
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Completion of treatment | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
|
|
Comparison 6. Intravenous drug users: choose own location versus treatment centre
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Completion of treatment | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
|
|
Table 1. Risk of bias assessmenta
|
| Trial | Randomization type | Allocation sequence generation | Allocation concealment | Blinding (assessors) | Completeness of follow up |
| | Chaisson 2001 | Individual | Adequate | Unclear | Inadequate | Inadequate |
| | Kamolratanakul 1999 | Individual | Adequate | Inadequate | Inadequate | Adequate |
| | Lwilla 2003 | Cluster | Unclear | Unclear | Inadequate | Inadequate |
| | MacIntyre 2003 | Individual | Inadequate | Inadequate | Adequate | Unclear |
| | Malotte 2001 | Individual | Unclear | Adequate | Inadequate | Unclear |
| | Newell 2006 | Cluster | Adequate | Inadequate | Adequate | Adequate |
| | Walley 2001 | Individual | Adequate | Adequate | Adequate | Unclear |
| | Wandwalo 2004 | Individual | Adequate | Inadequate | Inadequate | Adequate |
| | Wright 2004 | Individual | Unclear | Unclear | Adequate | Adequate |
| | Zwarenstein 1998 | Individual | Adequate | Adequate | Inadequate | Adequate |
| | Zwarenstein 2000 | Individual | Adequate | Adequate | Inadequate | Unclear |
|
|
aDetails of methods in the '.
|
