Drug-resistant tuberculosis treatment

Evidence base and analyses. Ahead of the GDG discussion, WHO made a public call for individual 
MDR/RR-TB patient data, complete with results of treatment (65). IPD meta-analysis in adults and 
children treated with longer MDR-TB regimens allows the study of useful correlates of outcome, 
including the regimen composition (61–63). The evidence base for the effectiveness of many of the 
medicines used in MDR-TB regimens relies on the IPD meta-analysis. In turn, the IPD meta-analysis 
relies heavily on observational studies, only a few of which have employed randomized controlled 
conditions (66); hence, the overall certainty in the evidence is often graded as low or very low. The 
sources of data used by the GDG to address the PICO questions in this section are summarized below. 
PICO question 3 (MDR/RR-TB, 2018) (choice of individual medicines). First, to analyse treatment 
success, treatment failure, relapse and death for the individual medicines in longer regimens, the 2018 
IPD meta-analysis was used, with 13 104 records from 53 studies in 40 countries. The 2018 IPD contains 
new datasets from recent years in several countries, including a large dataset from South Africa with many 
patients treated with bedaquiline-containing regimens. Second, to analyse adverse events resulting in 
permanent discontinuation of individual medicines in longer regimens, a subset of 5450 records from 
17 studies in the IPD was used, supplemented with additional information from 10 other studies that 
only reported adverse events for either bedaquiline (n=130), linezolid (n=508) or carbapenems (n=139).
In addition to these data, the GDG also assessed unpublished results from the Phase III Trial 213 of 
delamanid (67, 68), and safety and pharmacological exposure data from unpublished paediatric 
studies of bedaquiline (Phase II TMC207-C211 and Phase I/II IMPAACT P1108) and delamanid (Phase 
I 242–12–245, Phase I 242–12–232, Phase II 242–07–204 and Phase II 242–12–233) (see Annex 5). 
The GDG also searched the literature for studies reporting outcomes of patients treated with agents 
other than those included in the 2016 guidelines (e.g. perchlozone, interferon gamma and
sutezolid).