Conducting efficacy trials in children with MDR-TB: what is the rationale and how should they be done?

J. A. Seddon, Ethel Weld, H. S. Schaaf, A. J. Garcia-Prats, S. Kim, A. C. Hesseling

Research output: Contribution to journalArticle

Abstract

Paediatric anti-tuberculosis treatment trials have traditionally been limited to Phase I/II studies evaluating the drug pharmacokinetics and safety in children, with assumptions about efficacy made by extrapolating data from adults. However, it is increasingly being recognised that, in some circumstances, efficacy trials are required in children. The current treatment for children with multidrug-resistant tuberculosis (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 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 generalisability of such a trial, as 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 standardised 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.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalThe international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Volume22
Issue number5
DOIs
StatePublished - May 1 2018

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Multidrug-Resistant Tuberculosis
Pediatrics
Drug Resistance
Capacity Building
Safety
Poisons
Only Child
Therapeutics
Pharmaceutical Preparations
Tuberculosis
Pharmacokinetics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Conducting efficacy trials in children with MDR-TB : what is the rationale and how should they be done? / Seddon, J. A.; Weld, Ethel; Schaaf, H. S.; Garcia-Prats, A. J.; Kim, S.; Hesseling, A. C.

In: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, Vol. 22, No. 5, 01.05.2018, p. 24-33.

Research output: Contribution to journalArticle

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