Methodological considerations in clinical trials for new MDR-TB treatment regimens.

In contrast to the treatment of drug-susceptible tuberculosis (TB), the evidence base underpinning global guidelines for the treatment of multidrug-resistant (MDR) TB is very poor. This, combined with the lack of experience from previous trials and the nature of the disease, means that a number of methodological aspects are specific only to trials for new MDR-TB regimens. These aspects include the weight of evidence required to change policy and practice, the flexibility to make adaptations to an ongoing trial, the choice of patient population, the importance of internal control, the duration and frequency of follow-up, and safety monitoring of novel combinations of new and repurposed drugs.