RCT of directly observed therapy (DOT) for patients with pulmonary tuberculosis in Thailand

1 Did the study ask a clearly focused question?

Yes. Compared effectiveness of DOT with self-supervised (SS) drug administration regimens on 837 patients in three different types of health settings in Thailand

2 Was this an RCT and was it appropriately so?

Yes. Wanted to compare the effectiveness of two different therapy regimens. Participants randomly allocated to DOT and SS groups. No explanation offered as to why the study was necessary. i.e. why TB patients need supervision when taking their medication (presumably, unpleasant side-effects?)

3 Were participants appropriately allocated to intervention and control groups?

Seems so. An independent central study allocation unit employed random number tables to divide the patients into two groups. Used block randomisation to ensure even split of patients into both groups at each healthcare site.

No explanation of how allocation was performed is provided, and a separate scheme was used at each site. No explanation of why this was done, or whether it might have allowed for interference with the randomisation by the person doing the allocation.

4 Were participants, staff and study personnel ‘blind’ to participants’ study group?

No. Participants were not even informed they were in a study, let alone asked for informed consent, and no indication is given that ethical approval was obtained for the research. Investigators were also not blinded, which may explain the Hawthorn effect referred to later in the paper. (The Hawthorn effect occurs when participants in the control arm of a study do better than usual, probably because healthcare staff give them better care/observation than usual because they know that they are part of a research study.)

5 Were all of the participants who entered the trial accounted for at its conclusion?

Yes. Flow chart gives a clear description of who did what.Unusual for no participants to withdraw from a study. May be accounted for by the fact that participants were not asked for consent, and the seriousness of the condition, but follow-up appears top have been meticulous.

6 Were the participants in all groups followed up and data collected in the same way?

Some patients in the intervention arm were observed by healthcare personnel, others by family members or community members. (Expense may mean it’s not practical to have healthcare workers visiting patients to check they’re taking their medication on a daily basis.) Used pills were counted to check patients and relatives accounts of compliance (canny patients might simply have chucked away pills they ought to have taken but didn’t.) However, a second check on compliance with taking the rifamcipin by examining urine colour was more objective.

7 Did the study have enough participants to minimise the play of chance?

Sample size calculation was performed and recruitment designed to detect a significant difference in cure rate of 10% or higher. Considerably more patients (837) were recruited than needed (336). No explanation offered as to why this was so.

8 and 9 How are the results presented and how precise are they?

Main results show significantly better results for DOT over SS in terms of cure (p=0.004), completion of treatment (p=0.006), and default (p=0.005). I couldn’t see any explanation of what default meant, and how it was different from completion (or non-completion) of treatment. There were also significantly better results for DOT over SS in terms of transfer out of district (p=0.025) but no explanation is offered as to why this should be so, or why it might be relevant. Caseholding (p=0.002) was also significantly better for the DOT group, but I don’t understand what this term means. You’d normally expect confidence intervals to be provided alongside p values, showing the minimum and maximum likely differences between the effects being measured, but they aren’t provided here.

10 Were all important outcomes considered so the results can be applied?

Might Thai patients be more compliant with supervision provided by DOT than HMR residents?

May be easier in the HMR setting for health visitors to travel by car to provide DOT in patients own homes, than to travel 30 odd miles through a jungle.

Cost of improved compliance may need to be balanced against cost of providing more intensive therapy to SS non-compliers, or the risk of an increase in the prevalence of TB that untreated patients may pose (I’m assuming that pulmonary TB is contagious?!)