Journal Article > CommentaryFull Text
Int J Tuberc Lung Dis. 2020 November 1; Volume 24 (Issue 11); 1134-1144.; DOI:10.5588/ijtld.20.0330
Cox V, McKenna L, Acquah R, Reuter A, Wasserman S, et al.
Int J Tuberc Lung Dis. 2020 November 1; Volume 24 (Issue 11); 1134-1144.; DOI:10.5588/ijtld.20.0330
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second ‘Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
Journal Article > CommentaryFull Text
Lancet Child Adolesc Health. 2020 December 1; Volume 4 (Issue 12); 855-857.; DOI:10.1016/S2352-4642(20)30273-X
Nash M, Perrin C, Seddon JA, Furin J, Hauser J, et al.
Lancet Child Adolesc Health. 2020 December 1; Volume 4 (Issue 12); 855-857.; DOI:10.1016/S2352-4642(20)30273-X
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 2021 October 1; Volume 25 (Issue 10); 864-865.; DOI:10.5588/ijtld.21.0222
Deborggraeve S, Menghaney L, Lynch S, McKenna L, Branigan D
Int J Tuberc Lung Dis. 2021 October 1; Volume 25 (Issue 10); 864-865.; DOI:10.5588/ijtld.21.0222
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 December 1; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
du Cros PAK, Greig J, Cross GB, Cousins C, Berry C, et al.
Int J Tuberc Lung Dis. 2023 December 1; Volume 27 (Issue 12); 885-898.; DOI:10.5588/ijtld.23.0341
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BACKGROUND
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.
METHODS
A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.
RESULTS
Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.
CONCLUSION
These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.
Journal Article > CommentaryFull Text
Guglielmetti L, Low M, McKenna L
2020 April 28; Volume 18 (Issue 8); DOI:10.1080/14787210.2020.1756776
Journal Article > ReviewFull Text
Am J Respir Crit Care Med. 2016 November 17; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
Harausz EP, Garcia-Prats AJ, Seddon JA, Schaaf HS, Hesseling AC, et al.
Am J Respir Crit Care Med. 2016 November 17; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.
Journal Article > ResearchFull Text
PLOS One. 2021 August 31; Volume 16 (Issue 8); e0256883.; DOI: 10.1371/journal.pone.0256883
Gotham D, McKenna L, Deborggraeve S, Madoori S, Branigan D
PLOS One. 2021 August 31; Volume 16 (Issue 8); e0256883.; DOI: 10.1371/journal.pone.0256883
BACKGROUND
The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid's suite of cartridge-based assays.
METHODS
Public funding data were collected from the proprietor company's financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology's development. The value of research and development (R&D) tax credits was estimated based on financial filings.
RESULTS
Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business 'springboard' grants.
CONCLUSION
The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance agreements.
The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid's suite of cartridge-based assays.
METHODS
Public funding data were collected from the proprietor company's financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology's development. The value of research and development (R&D) tax credits was estimated based on financial filings.
RESULTS
Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business 'springboard' grants.
CONCLUSION
The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance agreements.
Journal Article > CommentaryFull Text
Lancet Microbe. 2023 July 31; Volume S2666-5247 (Issue 23); 00217-3.; DOI:10.1016/S2666-5247(23)00217-3
Branigan D, Denkinger CM, Furin J, Heitkamp P, Deborggraeve S, et al.
Lancet Microbe. 2023 July 31; Volume S2666-5247 (Issue 23); 00217-3.; DOI:10.1016/S2666-5247(23)00217-3
Journal Article > ResearchFull Text
Bull World Health Organ. 2023 November 1; Volume 101 (Issue 11); 730-737.; DOI:10.2471/BLT.23.290901
Gupta-Wright A, den Boon S, MacLean E, Cirillo DM, Cobelens F, et al.
Bull World Health Organ. 2023 November 1; Volume 101 (Issue 11); 730-737.; DOI:10.2471/BLT.23.290901
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The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment. The development of the target product profiles was informed by a stakeholder survey, a cost-effectiveness analysis and a patient-care pathway analysis. Additional feedback from stakeholders was obtained by means of a Delphi-like process, a technical consultation and a call for public comment on a draft document. A scientific development group agreed on the final targets in a consensus meeting. For characteristics rated of highest importance, the document lists: (i) high diagnostic accuracy (sensitivity and specificity); (ii) time to result of optimally ≤ 2 hours and no more than 1 day; (iii) required sample type to be minimally invasive, easily obtainable, such as urine, breath, or capillary blood, or a respiratory sample that goes beyond sputum; (iv) ideally the test could be placed at a peripheral-level health facility without a laboratory; and (v) the test should be affordable to low- and middle-income countries, and allow wide and equitable access and scale-up. Use of these target product profiles should facilitate the development of new tuberculosis treatment monitoring and optimization tests that are accurate and accessible for all people being treated for tuberculosis.
Journal Article > CommentarySubscription Only
Nat Med. 2023 January 1; Volume 29 (Issue 1); 16-17.; DOI:10.1038/s41591-022-02136-z
McKenna L, Frick M, Angami K, Dubula V, Furin J, et al.
Nat Med. 2023 January 1; Volume 29 (Issue 1); 16-17.; DOI:10.1038/s41591-022-02136-z