| Methods |
RCT: individual patients were contacted by telephone through a third party (who was unaware of any information about the patient) at the research‐team office, with a list of random allocations computer‐generated by the research team. To allow for the possibility of failed telephone contact, facilities were also provided with pre‐prepared allocations sealed in opaque envelopes. After randomization, the enrolment officer and the patient discussed and agreed on the details of the selected treatment protocol |
| Participants |
497 patients were enrolled in the trial. Each adult (aged 15 years or older) whose initial diagnosis at the diagnostic center was as a new case of sputum‐positive pulmonary tuberculosis was sent to the enrolment officer who interviewed the patient to confirm eligibility for enrolment; in particular, to confirm that no treatment for tuberculosis had been taken previously, and that the patient lived in one of the trial catchment areas. Urban Rawalpindi was a WHO‐sponsored "demonstration" site, patients in the demonstration site catchment area were excluded |
| Interventions |
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 first, and prevailing, strategy was self administered treatment, in which each patient collects drugs fortnightly from the most convenient health facility. The second was health worker direct observation of treatment, i.e. supervision by a health worker at a health facility when the patient met criteria for access to the facility, and by a community health worker at or near the patient's home otherwise. The access criteria, determined from the exploratory studies, were that the return journey from the patient's home to the health facility was a distance of less than 2 kilometers, a duration of less than 2 hours, and a cost of less than 10 rupees; and for unmarried women, an accompanying relative was to be available. The patient nominated the health facility most convenient for him or her. If the access criteria were met, a health worker at that facility was identified to supervise treatment; otherwise, a community health worker local to the patient's home and acceptable to the patient was chosen as supervisor. The supervisor was oriented on his or her role by a visiting field officer. The patient was then expected to attend the health facility or community health worker 6 times per week in the initial 2‐month intensive phase to take the drugs. In the 6‐month continuation phase, patients continued on self administered treatment, collecting drugs fortnightly from the most convenient health facility or community health worker. The third strategy was family‐member direct observation of treatment, that is, supervision by a family member. The patient was assisted in the selection of a concerned and influential family member as supervisor. The family member was oriented on his or her role. The patient (or family member) collected drugs fortnightly from the health facility most convenient for him or her. In both strategies involving direct observation of treatment, the supervisor was taught how to record drug‐taking using a specially designed form, and was made aware of the importance of observing drug‐taking and of encouraging the patient to complete treatment |
| Outcomes |
"Defaulted" in Table 2 used as a proxy for "noncompliant". Default was defined as failing to collect treatment from the health center for 2 consecutive months during the course of treatment. The outcome measures used were cure, and cure plus treatment completion |
| Notes |
― |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Method of randomization appropriate and well described. "Method of randomisation of individual patients was by telephone through a third party (who was unaware of any information about the patient) at the research‐team office in Islamabad, with a list of random allocations computer‐generated by the research team. To allow for the possibility of failed telephone contact, we also provided facilities with preprepared allocations sealed in opaque envelopes. As it happened, there were many problems with telephone contacts, and the envelope method of allocation was used for most cases. However, we are confident that this had no effect on the quality of randomisation." (pg 665) |
| Allocation concealment (selection bias) |
Low risk |
Allocation concealment described and appropriate. "...by telephone through a third party (who was unaware of any information about the patient) at the research‐team office in Islamabad, with a list of random allocations computer‐generated by the research team." (pg 665) |
| Selective reporting (reporting bias) |
Unclear risk |
No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol |
| Other bias |
Low risk |
The study seems to be free of other types of bias |
| Blinding of outcome assessment (detection bias)
Adherence measure |
Low risk |
(PRIMARY) TREATMENT COMPLETED RATE ‐ Outcomes assessors were blinded. "Outcome assessment was by laboratory examination of sputum by technicians unaware of treatment allocation". (pg 666) |
| Blinding of outcome assessment (detection bias)
Patient outcome |
Low risk |
(PRIMARY) CURE RATE ‐ Outcome assessors were blinded. "Outcome assessment was by laboratory examination of sputum by technicians unaware of treatment allocation" (pg 666) |
| Blinding of participants (performance bias)
Adherence measure |
Unclear risk |
(PRIMARY) TREATMENT COMPLETED RATE ‐ Patients were aware of treatment allocation but unclear if this would bias outcome. "After randomisation, the enrollment officer and the patient discussed and agreed the details of the selected treatment protocol" (pg 665) |
| Blinding of participants (performance bias)
Patient outcome |
Unclear risk |
(PRIMARY) CURE RATE ‐ Patients were aware of allocation but unclear if this would impact outcome. "After randomisation, the enrolment officer and the patient discussed and agreed the details of the selected treatment protocol" (pg 665) |
| Blinding of personnel (performance bias)
Adherence measure |
Low risk |
(PRIMARY) TREATMENT COMPLETED RATE ‐ Study personnel were blinded. "The doctor, health educator, laboratory technicians, and other regular staff of the diagnostic centre provided health education, and monitored the clinical aspects of care, side effects, sputum conversion, &c, following the same procedure for all patients. These staff were unaware of the trial group of the patients. The enrolment officer had no role in care provision." (pg 666) |
| Blinding of personnel (performance bias)
Patient outcome |
Low risk |
(PRIMARY) CURE RATE ‐ Study personnel were blinded. "The doctor, health educator, laboratory technicians, and other regular staff of the diagnostic centre provided health education, and monitored the clinical aspects of care, side effects, sputum conversion, &c, following the same procedure for all patients. These staff were unaware of the trial group of the patients. The enrolment officer had no role in care provision." (pg 666) |
| Incomplete outcome data (attrition bias)
Adherence measure |
Unclear risk |
(PRIMARY) TREATMENT COMPLETED RATE ‐ Reasons for missing data are not reported |
| Incomplete outcome data (attrition bias)
Patient outcome |
Unclear risk |
(PRIMARY) CURE RATE ‐ Reasons for missing data are not reported |
