To commemorate World TB Day, a Special Collection has been released by PLOS Medicine containing a series of articles that articulate the essential new steps in clinical research that will pave the way for the development of tomorrow’s optimal treatment for all forms of tuberculosis. This Special Collection is sponsored by the World Health Organization (WHO) and IRD-France, and is co-ordinated by Dr Christian Lienhardt, Research Director at IRD-France and Dr Payam Nahid, Professor at University of California, San Francisco, USA.
The series is the outcome of a technical consultation organized by WHO on 11-13th March 2018 on “Advances in Clinical Trial Design for New TB Treatments” to identify and outline, through expert consensus, the optimal characteristics of clinical trial designs to inform policy guidance for the development of new TB regimens. Building on the lessons learnt from a rich history of TB clinical trials, experts reviewed the various designs and tools currently used in the conduct of clinical trials and made a series of propositions to advance the field further, with a view to attaining the best quality data possible on new TB treatments. “To accelerate the development of new TB treatments it is essential to maximize sharing data and experiences and improve the way clinical trials are designed”, says Dr Matteo Zignol, Team Leader, Research for TB Elimination, Global TB Programme, WHO.
An iterative series of clinical trials undertaken in the 1970s and 1980s by the British Medical Research Council and the US Public Health Services established the modern day six-month regimen for drug susceptible TB. Since then, despite the arrival of two newly approved drugs in the market, progress to shortening duration of treatments for TB and improving tolerability of TB regimens has been unacceptably slow, with the treatment of drug-resistant TB still relying on a complex, poorly tolerated, combination of drugs administered for 9 to 20 months duration.
Development of new TB treatments will continue to be hampered by numerous challenges, ranging from the laboratory, with our reliance on mycobacteriology for endpoint definitions, to the field, wherein a clinical trial’s control arm needs to be selected and implemented in the face of rapidly changing policies. The most commonly touted challenge in TB therapeutics remains the absence of a surrogate marker that can be readily measured and that estimates with adequate certainty the anticipated treatment effect in late stage clinical development. New opportunities are emerging with the recent developments in PK/PD methodologies, novel clinical trial designs, new biomarkers, as well as recent advances in molecular diagnostics. A recently broadened and exciting pipeline of new candidate drugs compels us to revisit our current approaches to TB drug development, and based on the learnings of the last 50 years, to identify and seek consensus on best practices for future TB clinical trial designs. “We are at an unprecedented cross point at which reflections on a rich history of clinical trials meet new advances in methodological methods and technologies to move forward research and approaches for new TB treatments”, says Dr Christian Lienhardt.
The PLOS Medicine Special Collection launched on the 22nd March 2019 introduces a series of articles that articulate the essential new steps in clinical research that will pave the way for the development of tomorrow’s optimal treatment for all forms of TB.