Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand. A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting. Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial. Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district, Tanzania. Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan. Direct observation of treatment for tuberculosis: a randomized controlled trial of community health workers versus family members. Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis. Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa. Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial. Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste. Incentives vs outreach workers for latent tuberculosis treatment in drug users.
While directly observed treatment (DOT) has been recommended as the standard approach to tuberculosis control, empirical data on its feasibility and efficiency are still scarce. We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thailand. A total of 836 patients diagnosed between August 1996 and October 1997 were randomly assigned to be treated either under DOT or self-supervised using monthly drug supplies (SS). Options for treatment supervisors were health staff, community members or members of the patients' families. Treatment outcomes were compared on the basis of cure, treatment-completion, default and death rates. In both study arms, treatment outcomes were improved compared to pre-study conditions. Cure and treatment-completion rates were significantly higher in the DOT cohort (76% and 84%) than in the SS group (67% and 76%). The benefits of DOT were more pronounced at district and provincial hospitals (DOT cure rate 81% vs. 69% in the SS group), while differences for patients treated at referral centres were non-significant (DOT cure rate 72% vs. 66% in the SS group). No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors. DOT appears especially suited for treatment at decentralized facilities. While a general focus on programme performance can improve outcomes, DOT provides significant additional benefits. If basic conditions are met, a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options, without decreasing its effectiveness. A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis.
                TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used.
                Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance.
                We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients. An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload.
                To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania.
                Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat.
                A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83).
                Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes. Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities. DOTS is the control strategy for tuberculosis promoted by WHO. Pakistan is currently developing its National Tuberculosis Programme, and requires guidance on types of direct observation of treatment appropriate for the local conditions. We did a randomised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan.
                We enrolled 497 adults with new sputum-positive tuberculosis. 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members; and 162 were assigned self-administered treatment. The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purposes of the research, with a standard daily short-course drugs regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 6 months of isoniazid and ethambutol). The main outcome measures were cure, and cure or treatment completion. Analysis was by intention to treat.
                Within the strengthened tuberculosis services, the health-worker DOTS, family-member DOTS, and self-administered treatment strategies gave very similar outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or treatment-completed rates of 67%, 62%, and 65%, respectively.
                None of the three strategies tested was shown to be superior to the others, and direct observation of treatment did not give any additional improvement in cure rates. The effectiveness of direct observation of treatment remains unclear, and further operational research is needed. We implemented community-based direct observation of treatment, short course (DOTS), including a randomized controlled trial of direct observation either by community health workers (CHWs) or family members, under operational conditions in a region of Swaziland. There was a high death rate of 15%, due to the high HIV rates in the region. There was no significant difference in the cure and completion rate between direct observation of treatment by CHWs and family members [2% difference (95% CI -3% to 7%), exact P = 0.52]. A before-and-after comparison of outcomes demonstrated that the cure and treatment completion rate improved from a baseline of 27-67% following implementation of community-based DOTS. We conclude that community-based tuberculosis DOTS can improve successful outcomes of treatment. However, direct observation can be undertaken effectively using either daily family or CHW supervision. The choice of treatment supporter should be based on access, patient preference and availability of CHW resource. Tuberculosis is a major public-health problem in South Africa, made worse by poor adherence to and frequent interruption of treatment. Direct observation (DO) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome. We compared DO with self-supervision, in which patients on the same drug regimen are not observed taking their pills, to assess the effect of each on the success of tuberculosis treatment.
                We undertook an unblinded randomised controlled trial in two communities with large tuberculosis caseloads. The trial included 216 adults who started pulmonary tuberculosis treatment for the first time, or who had a second course of treatment (retreatment patients). No changes to existing treatment delivery were made other than randomisation. Analysis was by intention to treat. Individual patient data from the two communities were combined.
                Treatment for tuberculosis was more successful among self-supervised patients (60% of patients) than among those on DO (54% of patients, difference between groups 6% [90% CI -5.1 to 17.0]). Retreatment patients had significantly more successful treatment outcomes if self-supervised (74% of patients) than on DO (42% of patients, difference between groups 32% [11%-52%]).
                At high rates of treatment interruption, self-supervision achieved equivalent outcomes to clinic DO at lower cost. Self-supervision achieved better outcomes for retreatment patients. Supportive patient-carer relations, rather than the authoritarian surveillance implicit in DO, may improve treatment outcomes and help to control tuberculosis. To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%.
                A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment.
                The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation.
                This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required. A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas.
                Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat.
                Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS.
                The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy. To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis.
                Parallel group randomised controlled trial.
                Three primary care clinics in Dili, Timor-Leste.
                270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis.
                Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes.
                Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3).
                Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required.
                Clinical Trials NCT0019256. Drug users are at increased risk for latent tuberculosis infection (LTBI) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease. Directly observed therapy (DOT) provided by outreach workers, the use of incentives, or both have been suggested as a means to increase adherence.
                To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users.
                The research design was a randomized controlled trial in a community outreach program setting. Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT. Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant (active outreach) and a $5 per visit incentive. Condition 2 was comprised of active outreach with no monetary incentive, and Condition 3, provision of DOT at the study community site and a $5 per visit incentive. The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen.
                The percentage of prescribed medication taken was higher for those who received incentives, either with (71%) or without (68%) active outreach, compared to those who received active outreach alone (13%). Only 4% of participants assigned to Condition 2 completed treatment, compared to 53% of Condition 1 participants, and 60% of Condition 3 participants.
                Monetary incentives were clearly superior to active outreach. Active outreach in combination with monetary incentives did not increase adherence over incentives alone.
The results of randomized controlled trials conducted in low-, middle-, and high-income countries provide no assurance that DOT compared with self administration of treatment has any quantitatively important effect on cure or treatment completion in people receiving treatment for tuberculosis.