Researchers from the MRC Clinical Trials unit in London have contributed to an essay published in the journal Public Library of Science Medicine (PLoS Med) that calls for involvement of children in trials to evaluate tuberculosis treatment regimens.
The lead author is William Burman of Denver Public Health and the University of Colorado Health Sciences Center in Denver USA. Professor Diana Gibb and Dr Sarah Walker, who both work on trials to find the best ways to manage HIV-infected children in Africa, also contributed.
The researchers argue that it is critical to involve children in evaluation of TB treatments because the doses known to work for adults don’t have the same beneficial effects in children. In countries where many people are infected with TB, children make up as much as 20% of new cases of active tuberculosis. Young children are especially at high risk of having severe, rapidly-progressive forms of the disease.
The authors write that 40 years after short-course regimens have been developed for adults, there are still major uncertainties about dosing of common TB drugs to treat children.
“Only in recent years has there been a substantial effort to manufacture child-friendly formulations of first-line tuberculosis drugs such as crushable mini-pills, granules, oral suspensions,” say the authors. “And in the past 15 years, children have been included in only one study of new agents for tuberculosis: a large Phase 3 trial evaluating once-weekly rifapentine plus isoniazid for treatment of latent tuberculosis.”
Design of effective drug regimens is further complicated by HIV-related immunodeficiency and resistance to TB drugs, both of which make it more difficult to control TB infection.
In the essay Burman and colleagues outline several traditional barriers to the involvement of children in tuberculosis drug development. These include difficulty confirming TB diagnosis, concern about side effects, and regulatory requirements. They also describe how these barriers can be overcome, arguing that researchers, regulatory agencies, advocates, government agencies and private foundations that fund drug development could insist that the development pathways for all new treatments include specific plans for when and how children will be involved.
“Children have the same right to benefit from research as do adults,” say the authors. “While this lack of involvement may be understandable in the short-term, it is not acceptable in the long-term.”
(Source: Public Library of Science Medicine: Medical Research Involving Children: September 2008)