Health technology assessment of fixed-dose combination regimen in treatment of newly diagnosed smear-positive pulmonary tuberculosis: A meta-analysis

Background Evidence-based policy decision-making is introduction of newer technology that it is 'not inferior' to existing technology. Multiple randomised clinical trials (RCTs) on tuberculosis (TB) treatment have shown mixture of favourable, unfavourable and non-significant changes in outcomes with the use of fixed-dose combination (FDC) regimens. The aim of this study was to assess clinical effectiveness of FDC regimen as compared to the use of separate drugs in anti-TB treatment. Methods Systematic literature search was carried out. RCTs with newly diagnosed smear-positive pulmonary TB cases were included. Defined outcomes were smear conversion, relapse, adverse reactions and patient compliance. Results Initial search revealed 457 articles, out of which 7 were included for meta-analysis. Pooled risk ratio for smear conversion rate at the end of intensive phase was 1.01 (95% confidence interval [CI], 0.99-1.03; p = 0.40). Similarly, smear conversion rate at the end of treatment showed no significant difference (relative risk (RR) = 1.01; 95% CI, 0.99-1.02; p = 0.45). Pooled risk ratio for combined smear conversion rates was 1.01 (95% CI, 0.99-1.02). However, relapse rates showed marginally higher trend with FDC regimens (RR, 1.56; 95% CI, 0.95-2.56; p = 0.49). Pooled analysis for adverse events showed no significant difference (RR = 0.98; 95% CI, 0.86-1.11; p = 0.70). Analysis of patient compliance showed marginal increase among FDC group (RR = 1.02; 95% CI, 0.96-1.09; p = 0.47)). Conclusion Fixed-dose combination (FDC) formulations are not inferior in treatment outcomes. It may also ease programme managers and patients by improving compliance. However, increase in relapse rates needs further evaluation through large multicentric studies before implementing policy change in the national programme.