Advances in clinical trial design: Weaving tomorrow’s TB treatments

Lienhardt, Christian; Nunn, Andrew; Chaisson, Richard E.; Vernon, Andrew; Zignol, Matteo; Nahid, Payam; Delaporte, Éric; Kasaeva, Tereza

doi:10.1371/journal.pmed.1003059

Cited by 18 publications

(15 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The intervention model in PACTR-registered trials indicates that registries may need to adapt to the changing trial designs, as seen with the current COVID-19 trials where adaptive trial designs were used 19–21. Our analysis shows that the most common intervention model was factorial assignment (20%).…”

Section: Discussionmentioning

confidence: 82%

Practices and trends in clinical trial registration in the Pan African Clinical Trials Registry (PACTR): a descriptive analysis of registration data

et al. 2022

View full text Add to dashboard Cite

BackgroundThe Pan African Clinical Trials Registry (PACTR) is a WHO International Clinical Trials Registry Platform primary register, which caters for clinical trials conducted in Africa. PACTR is the first and, at present, the only member of the Network of WHO Primary Registers in Africa. The aim is to describe and report on the trends of trial records registered in PACTR.MethodsPACTR was established in 2007 as the AIDS, Tuberculosis, and Malaria Clinical Trials Registry. The scope of the registry was then expanded in 2009 to include all diseases. This is a cross-sectional study of trials registered in PACTR from inception to 18 August 2021. A descriptive analysis of the use and trends of the following data fields: study intervention, disease condition, sex of the participants, sample size, ethics, funding and availability of results was conducted using Microsoft Excel.ResultsThe number of trials registered has increased year on year, reaching 606 trials registered in 2020. The total number of trials registered at the time of the analysis was 2998. More than half of the trials in the registry (1655 of 2998, ie, 55%) were prospectively registered. Ethical approval was received by 90% (2691 of 2998) of the registered trials. Factorial assignment as an intervention model was in 20% (589 of 2998) of the trials registered. There were 36% (1083 of 2998) completed trials, of which 3% (94 of 1083) had results available in the registry. The most dominant funding source indicated was self-funding in 23% (693 of 2998) of the registered trials, and 55% (1639 of 2998) had no funding.ConclusionRegistration on PACTR continues to grow; however, our analysis shows that researchers’ capacity-building is needed to understand the importance of the registry and how this information informs healthcare decisions. Promoting prospective trial registration remains critical to avoid selective reporting bias to inform research gaps.

show abstract

Section: Discussionmentioning

confidence: 82%

Practices and trends in clinical trial registration in the Pan African Clinical Trials Registry (PACTR): a descriptive analysis of registration data

et al. 2022

View full text Add to dashboard Cite

show abstract

“…S2). Despite the considerable challenges associated with TB drug development ( 92 ), progress has been accelerated from sustained funding and guidance by organizations such as the TB Alliance and the Gates Foundation ( 93 ). The next challenge will be to move the most promising candidates through the pipeline and select and clinically evaluate the optimal drug regimens.…”

Section: Analysis and Discussionmentioning

confidence: 99%

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

Butler

Gigante²,

Sati³

et al. 2022

Antimicrob Agents Chemother

Self Cite

172

View full text Add to dashboard Cite

There is an urgent global need for new strategies and drugs to control and treat multi-drug resistant bacterial infections. In 2017, the World Health Organization (WHO) released a list of 12 antibiotic-resistant priority pathogens and began to critically analyze the antibacterial clinical pipeline. This review analyzes ‘traditional’ and ‘non-traditional’ antibacterial agents and modulators in clinical development current on 30 June 2021 with activity against the WHO priority pathogens, mycobacteria and Clostridioides difficile. Since 2017, 12 new antibacterial drugs have been approved globally, but only vaborbactam belongs to a new antibacterial class. Also innovative is the cephalosporin derivative cefiderocol, which incorporates an iron-chelating siderophore that facilitates Gram-negative bacteria cell entry. Overall, there were 76 antibacterial agents in clinical development (45 traditional and 31 non-traditional) with 28 in Phase 1, 32 in Phase 2, 12 in Phase 3 and four under regulatory evaluation. Forty-one out of 76 (54%) targeted WHO priority pathogens, 16 (21%) against mycobacteria, 15 (20%) against C. difficile and 4 (5%) are non-traditional agents with broad spectrum effects. Nineteen of the 76 antibacterial agents have new pharmacophores and four of these have new modes of actions not previously exploited by marketed antibacterial drugs. Despite there being 76 antibacterial clinical candidates, this analysis indicated that there were still relatively few clinically differentiated antibacterial agents in late-stage clinical development, especially against critical Priority Pathogens. We believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways to the market.

show abstract

“…New initiatives, such as the the European Union (EU) Innovative Medicines Initiative IMI2 call and the Gates Medical Research Institute alliance, have the potential to accelerate research and synergize with existing efforts carried out by academia, public-private partnerships, such as the TB Alliance, and industry. If researchers collaborate and join forces towards the common aim of innovative regimens, there is a possibility of pursuing effectively a transformational improvement of treatment of all forms of TB [25]. If, however, such initiatives compete for limited resources and resist cooperation, the targets expressed at the time of the Moscow Conference in late 2017 and subsequently at the United Nations General Assembly in 2018 may remain a dream.…”

Section: Discussionmentioning

confidence: 99%

TB Elimination Requires Discovery and Development of Transformational Agents

Lienhardt

Raviglione

2020

Applied Sciences

Self Cite

View full text Add to dashboard Cite

The World Health Organization (WHO) End Tuberculosis (TB) Strategy has set ambitious targets to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. Given the current rate of TB incidence decline (about 2% per year annually), reaching these targets will require new transformational tools and innovative ways to deliver them. In addition to improved tests for early and rapid detection of TB and universal drug-susceptibility testing, as well as novel vaccines for improved prevention, better, safer, shorter and more efficacious treatments for all forms of TB are needed. Only a handful of new drugs are currently in phase II or III clinical trials, and a few combination regimens are being tested, mainly for drug-resistant TB. In this article, capitalising on an increasingly rich medicine pipeline and taking advantage of new methodological designs with great potential, the main areas where progress is needed for a transformational improvement of treatment of all forms of TB are described.

show abstract

Advances in clinical trial design: Weaving tomorrow’s TB treatments

Cited by 18 publications

References 50 publications

Practices and trends in clinical trial registration in the Pan African Clinical Trials Registry (PACTR): a descriptive analysis of registration data

Practices and trends in clinical trial registration in the Pan African Clinical Trials Registry (PACTR): a descriptive analysis of registration data

Analysis of the Clinical Pipeline of Treatments for Drug-Resistant Bacterial Infections: Despite Progress, More Action Is Needed

TB Elimination Requires Discovery and Development of Transformational Agents

Contact Info

Product

Resources

About