Towards early inclusion of children in tuberculosis drugs trials: a consensus statement

Sharon Nachman; Amina Ahmed; Farhana Amanullah; Mercedes C Becerra; Radu Botgros; Grania Brigden; Renee Browning; Elizabeth Gardiner; Richard Hafner; Anneke Hesseling; Cleotilde How; Patrick Jean-Philippe; Erica Lessem; Mamodikoe Makhene; Nontombi Mbelle; Ben Marais; Helen McIlleron; David F McNeeley; Carl Mendel; Stephen Murray; Eileen Navarro; E Gloria Anyalechi; Ariel R Porcalla; Clydette Powell; Mair Powell; Mona Rigaud; Vanessa Rouzier; Pearl Samson; H Simon Schaaf; Seema Shah; Jeff Starke; Soumya Swaminathan; Eric Wobudeya; Carol Worrell

doi:10.1016/S1473-3099(15)00007-9

Towards early inclusion of children in tuberculosis drugs trials: a consensus statement

Lancet Infect Dis. 2015 Jun;15(6):711-20. doi: 10.1016/S1473-3099(15)00007-9. Epub 2015 May 6.

Authors

Sharon Nachman¹, Amina Ahmed², Farhana Amanullah³, Mercedes C Becerra⁴, Radu Botgros⁵, Grania Brigden⁶, Renee Browning⁷, Elizabeth Gardiner⁸, Richard Hafner⁷, Anneke Hesseling⁹, Cleotilde How¹⁰, Patrick Jean-Philippe¹¹, Erica Lessem¹², Mamodikoe Makhene⁷, Nontombi Mbelle¹³, Ben Marais¹⁴, Helen McIlleron¹⁵, David F McNeeley¹⁶, Carl Mendel⁸, Stephen Murray⁸, Eileen Navarro¹⁷, E Gloria Anyalechi¹⁸, Ariel R Porcalla¹⁷, Clydette Powell¹⁹, Mair Powell⁵, Mona Rigaud²⁰, Vanessa Rouzier²¹, Pearl Samson²², H Simon Schaaf⁹, Seema Shah²³, Jeff Starke²⁴, Soumya Swaminathan²⁵, Eric Wobudeya²⁶, Carol Worrell²⁷

Affiliations

¹ SUNY at Stony Brook, Stony Brook, NY, USA. Electronic address: sharon.nachman@stonybrook.edu.
² Levine Children's Hospital at Carolinas Medical Center, Charlotte, NC, USA.
³ Indus Hospital, Pakistan.
⁴ Harvard Medical School, Boston, MA, USA.
⁵ European Medicines Agency, London, UK.
⁶ Médecins Sans Frontières, Access Campaign, Geneva, Switzerland.
⁷ National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD, USA.
⁸ TB Alliance, New York, NY, USA.
⁹ Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
¹⁰ Department of Pharmacology and Toxicology, University of the Philippines, Manila, Philippines.
¹¹ Henry M Jackson Foundation-Division of AIDS, Contractor to National Institutes of Health, National Institute of Allergy and Infectious Diseases, Department of Health and Human Services, Bethesda, MD, USA.
¹² Treatment Action Group, New York, NY, USA.
¹³ Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
¹⁴ Marie Bashir Institute for Infectious Diseases and Biosecurity and the Sydney Emerging Infectious Diseases and Biosecurity Institute and The Children's Hospital at Westmead, Sydney Medical School, University of Sydney, Sydney, Australia.
¹⁵ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.
¹⁶ Novartis Pharmaceuticals, East Hanover, NJ, USA.
¹⁷ Division of Anti-Infective Products; Office of Antimicrobial Products, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
¹⁸ US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, International Research and Programs Branch, Atlanta, GA, USA.
¹⁹ US Agency for International Development, Washington, DC, USA.
²⁰ New York University School of Medicine, NY, USA.
²¹ GHESKIO, Port-au-Prince, Haiti.
²² Statistical and Data Analysis Center, Center for Biostatistics in AIDS Research and Frontier Science, Harvard School of Public Health, Boston, MA, USA.
²³ Department of Bioethics, NIH Clinical Center, Bethesda, MD, USA.
²⁴ Baylor College of Medicine, Houston, TX, USA.
²⁵ National Institute for Research in Tuberculosis, Chennai, India.
²⁶ Makerere University Johns Hopkins Research Collaboration, and Mulago National Referral Hospital, Kampala, Uganda.
²⁷ Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA.

Abstract

Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Review

MeSH terms

Adolescent
Adult
Age Factors
Antitubercular Agents / therapeutic use*
Child
Child, Preschool
Clinical Trials as Topic*
Consensus
Female
Humans
Infant
Infant, Newborn
Male
Tuberculosis / drug therapy*

Substances

Antitubercular Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding