Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan

Background 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. Methods 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. Findings 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. Interpretation 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.