WHO strongly supports global sharing of data from TB clinical trials to maximize learning and accelerate discoveries
06 November 2018 | Geneva: To advance the development of new treatments against all forms of TB and maximize the impact of studies and trials undertaken in this area, WHO and partners have initiated a series of pioneering initiatives over the past few years. These are now bearing fruit.
“Enhancing and optimizing global data sharing efforts is critical to make the most of existing evidence” said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme. “Findings from pooled analyses will drive vital discoveries that can improve TB diagnosis and cure worldwide and potentially reduce the global burden of suffering and death caused by this top infectious killer”.
The various initiatives led by WHO with partners include:
- The development of WHO guidance in 2016, describing Target Regimen Profiles for new TB treatment, aimed at guiding the development process towards important TB treatment regimen characteristics. The document was developed through wide consultations with experts and stakeholders worldwide.
- Following this, and in order to facilitate the implementation of these target profiles by all relevant stakeholders, the WHO Global TB Programme organized a Technical Consultation on Advances in Clinical Trial Design for Development of New TB Treatments in March 2018 in Glion-sur-Montreux, Switzerland. The objective was to identify and outline the various innovations needed in TB clinical trial design to develop new TB regimens and inform policy guidance for their implementation. The report of the technical consultation describes areas of expert consensus on advances needed in various domains, such as pharmacokinetics/pharmacodynamics, microbiology and biomarkers; Phase II to Phase III transition; new Phase III trial designs; treatment adherence and special populations. (Read more here).
- In parallel, the first data from the Platform for Aggregation of Clinical TB Studies (TB-PACTS), launched by the WHO Special Programme for Research and Training in Tropical Diseases (TDR) in collaboration with the C-Path Institute to catalyze and accelerate TB research by standardizing Phase III TB clinical trial data and making these data available to the research community (here) were used by the WHO Global TB Programme and partners (including the Critical Path to TB Drug Regimens (CPTR) initiative, WHO/TDR and the University of California, San Francisco) in the TB-ReFLECT collaboration. The objective was to undertake cutting-edge analyses of data from three leading contemporary Phase III studies (OFLOTUB, REMox, and RIFAQUIN trials), all published in 2014 in the New England Journal of Medicine, which were the first to evaluate the treatment-shortening potential of quinolone-containing regimens in a systematic and controlled way. Through this analysis, it was expected to get an improved understanding of the factors responsible for the variability in TB patients’ response to treatment. The results of the analysis highlight the immense value of data sharing and pooled-analyses to the TB research community. Using the TB-PACTS platform, the pooled analysis of patient-level data from the above trials identified a series of patients’ characteristics that would make them eligible for either a four-month or a longer treatment.
“The sharing of data and re-analyses was essential to draw the lessons from the negative results of the three treatment shortening trials published in 2014, to try and understand more deeply the challenges the community faces in terms of treatment shortening trials” said Dr Christian Lienhardt, from the Institute for Research in Development (IRD) in Montpellier (France), who initiated the WHO Technical Consultation and the TB-ReFLECT project.
The first analysis using the TB-PACTS platform was published online this week in Nature Medicine (here).The analysis of data from 3405 participants found that four-month regimens were as effective in achieving cures as six months duration regimens in patients with minimal disease defined by low sputum smear grade or non-cavitary disease. Conversely, higher severity of disease defined a “hard-to-treat” population who would need more than the standard 6-month treatment duration in order to achieve the highest possible cure rates. According to Dr. Rada Savic, Associate Professor, University of California, San Francisco, who led the analyses, “regimen duration could be selected with greater precision to improve treatment outcomes and this approach should be tested in future clinical trials”.
“The results of this analysis are important not only for research & development, but also for the development and implementation of policies” said Dr. Matteo Zignol, Team Leader, Research for TB Elimination at the WHO’s Global Tuberculosis Programme. “WHO will continue to facilitate and support data sharing efforts to maximize learning, accelerate discoveries and advance global policies”.