Conducting efficacy trials in children with multidrug-resistant tuberculosis: what is the rationale and how should they be done?

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Title: Conducting efficacy trials in children with multidrug-resistant tuberculosis: what is the rationale and how should they be done?
Authors: Seddon, JA
Weld, E
Simon, S
Antony, G-P
Kim, S
Hesseling, A
Item Type: Journal Article
Abstract: Traditionally paediatric tuberculosis (TB) treatment trials have been limited to phase I/II studies evaluating the pharmacokinetics and safety of drugs in children, with assumptions about efficacy made by extrapolating data from adults. However, it is increasingly recognised that in some circumstances, efficacy trials are warranted and required in children. The current treatment for children with multidrug-resistant (MDR)-TB is long and toxic; shorter, safer regimens, using novel agents require urgent evaluation. Given the changing pattern of drug metabolism, disease spectrum and rates of TB disease confirmation with age, decisions around inclusion criteria require careful consideration. The most straightforward MDR-TB efficacy trial would include only children with confirmed MDR-TB and with no additional drug resistance. Given that it may be unclear at the time treatment is initiated whether the diagnosis will ultimately be confirmed and what the final drug resistance profile will be, this presents a unique challenge in children. Recruiting only these children would however limit the generalizability of such a trial since, in reality, the majority of children with TB do not have bacteriologically confirmed disease. Given the good existing treatment outcomes with current routine regimens for children with MDR-TB, conducting a superiority trial may not be the optimal design. Demonstrating non-inferiority of efficacy but superiority with regard to safety, would be an alternative strategy. Using standardized control and experimental MDR-TB treatment regimens is challenging given the wide spectrum of paediatric disease. However, using variable regimens would make interpretation challenging. A paediatric MDR-TB efficacy trial is urgently needed, and with global collaboration and capacity building, is highly feasible.
Date of Acceptance: 3-Dec-2017
ISSN: 1027-3719
Publisher: International Union Against Tuberculosis and Lung Disease
Journal / Book Title: International Journal of Tuberculosis and Lung Disease
Keywords: 1102 Cardiovascular Medicine And Haematology
Publication Status: Accepted
Appears in Collections:Department of Medicine
Faculty of Medicine

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