Sputum culture conversion is often used as an early microbiological endpoint in phase II clinical trials of TB treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible TB. This study aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) TB.
According to a commentary, regulatory review balances the incomplete understanding of new drugs against the magnitude and severity of unmet medical need. It notes that an imbalance of these factors 25 years ago in patients with HIV led to biomarker-facilitated accelerated approvals by the FDA and conditional market authorisations by the EMEA. It suggests that a similar therapeutic crisis is now faced for drug-resistant bacterial infections and it is time again for regulatory innovation in which Special Medical Use authorisation, restricted to specific patient populations, could result from small clinical trials, and potentially mandate reporting of clinical outcomes in lieu of phase 3 trials, which is commensurate with the urgency of the global multidrug-resistant TB crisis.