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Printable Handouts
Navigable Slide Index
- Introduction
- Overview
- How do we distinguish post-treatment positives?
- Trial end points in phase III trials
- REMoxTB trial (1)
- So how do we distinguish strains in TB trials?
- EMA definition of relapse
- Summary of standard IS6110 method
- MIRU sites
- Size estimation methods
- VNTR/MIRU sizing table in base pairs
- The impact of WGS on determining the end point
- Questions to be addressed
- Natural transmission in a TB outbreak (1)
- Natural transmission in a TB outbreak (2)
- A population based study
- Definitions from epidemiological studies
- REMoxTB trial (2)
- RIFAQUIN study
- REMoxTB trial results
- RIFAQUIN results
- Mixed infection
- Identification of mixed infection
- Mixed infection in the REMoxTB study
- What more detail can we find?
- Cross-contamination in myobacteriology
- Post-treatment positives
- How to interpret post-treatment positives
- WGS results of REMoxTB study
- Possible outcomes from WGS
- REMoxTB patients
- WGS in RIFAQUIN trial to distinguish relapse from reinfection?
- Comparison between WGS and MIRU-VNTR
- Comparative utility of WGS and MIRU-VNTR
- But is this the whole genome?
- WGS in patient selection
- Using WGS to detect resistance
- What would WGS deliver?
- Tools to deliver DST result
- Conclusions
- Challenges to overcome
- References
- Acknowledgements
Topics Covered
- Introduction to tuberculosis clinical trials and M. tuberculosis typing
- Understanding mixed infections and their impact on clinical trials
- How to distinguish relapse from reinfection and to determine emergent resistant strains
- How to establish such methods in the context of trials
- outlining the challenges that are still to be overcome
Links
Series:
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Talk Citation
Gillespie, S. (2021, July 28). Application of whole genome sequencing in tuberculosis clinical trials [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 6, 2024, from https://doi.org/10.69645/RUKO8821.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Stephen Gillespie is in receipt of research grants from MMRC, EDCTP, Global Alliance for TB Drug Development. Professor Gillespie’s involvements in clinical trials are supported by active and placebo drug supplies from Bayer Schering Health Care and Sanofi Aventis, while also providing support with regulatory and drug safety advice. Neither company has a managerial role within the study, however. Professor Gillespie has also provided training to senior staff at Bayer Schering Health Care.
Other Talks in the Series: Genomics and Clinical Microbiology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name's Stephen Gillespie.
I'm the Sir James Black Professor of Medicine at the University of St. Andrews.
I'm going to talk today about the application of
whole genome sequencing in tuberculosis clinical trials.
0:14
In this talk, I will introduce the basic concepts of the tuberculosis clinical trial.
After providing a background of the evolution of
typing techniques apply to microbacteriology,
I will show the way in which
genome sequencing can assist in performing clinical trials better.
The areas covered will include defining relapse
and reinfection, detecting mixed infection,
using genomics to understand the significance of
post-treatment positives and conclude with some observations,
and how this exciting technology could be applied more widely in clinical trials.
0:51
This image represents the overview of the REMoxTB clinical trial,
the first of the modern-day studies using
regulatory methods and genomic techniques to contribute to the result.
Here you can see the treatment plans for the study
which compares the standard isoniazid, rifampicin,
ethambutol and pyrazinamide regimen with two experimental regimens that
substitute moxifloxacin and fluoroquinolones for either ethambutol or isoniazid.
The patients are treated for
four or six months and are followed for a year after the completion of treatment.
All of the patients had to be culture-positive to be included in the analysis.
In total, the patients attended 16 visits over their participation in the trial.
The isolates from patients who either failed on treatment or
had an apparent recurrence were collected as indicated.
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