Short-course TB therapy fails in three international trials

Although the studies described here have established the capacity for large, multicenter trials across disease-endemic countries, the design and selection of future experimental regimens will need to incorporate a triage process that can mitigate risks while enabling the accelerated development of much-needed treatment-shortening therapies. The disconnect between the phase II data that motivated these trials and the phase III results reinforces the idea that small sample sizes limit the utility of short trials in predicting the success of treatment-shortening regimens.

As these three trials have confirmed, our understanding of the science underlying positive clinical outcomes remains rudimentary. It’s time to go back to basics.

Digby F. Warner, Ph.D., and Valerie Mizrahi, Ph.D., are in the molecular mycobacteriology research unit at the Institute of Infectious Disease and Molecular Medicine, Cape Town and in the department of clinical laboratory sciences at the University of Cape Town, both in South Africa. Dr. Warner reported receiving funding from the South African Medical Research Council, Medical Research Foundation South Africa, and Wellcome Trust. Dr. Mizrahi reported funding from the European & Developing Countries Clinical Trials Partnership, the Bill and Melinda Gates Foundation, the Wellcome Trust, and USAID. Dr. Mizrahi also serves on the scientific advisory committee of the Global Alliance for TB Drug Development, which supported Dr. Gillespie’s study. This comment is excerpted from an editorial by Dr. Warner and Dr. Mizrahi that accompanied the three reports (N. Engl. J. Med. 2014 Oct. 23 [doi:10.1056/NEJMe1410977]).