Advances in clinical trial design for development of new TB treatments: A call for innovation

After decades of stagnation, research in tuberculosis (TB) therapeutics is experiencing a renaissance, with an increasing number of new and repurposed compounds undergoing evaluation as part of novel treatment regimens. This is much welcome progress, since current regimens are not ideal due to the long duration of treatment required, toxicities, drug-drug interactions, and high costs-particularly for treatment of the various forms of drug-resistant TB (DR-TB). The development of new TB drugs is, however, complex, lengthy, and costly [1], and the pathway to proven new TB treatment regimens is fraught with numerous obstacles and uncertainties In this PLOS Medicine Collection, "Advances in Clinical Trial Design for Development of New Tuberculosis Treatments," we highlight key obstacles and identify potential solutions that will help avoid misadventures and in turn maximize the likelihood of success in identifying new drugs and regimens through a rejuvenated global interest in TB therapeutics. With the emergence of several new chemical entities expected to transition into clinical testing in the next 5 years, the possibility of ultrashort (i.e., requiring treatment for weeks rather than months) regimens for active TB is no longer fanciful. Investigators in the field have learned much from recent TB clinical studies, and we anticipate that well-designed and conducted clinical trials evaluating the next generation of drugs and regimens will, with some good fortune, lead to identification of the ultrashort, safe, and effective regimens so desperately needed.