title: Towards early inclusion of children in tuberculosis drugs trials: a consensus statement.
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.
authors.affiliation: SUNY at Stony Brook, Stony Brook, NY, USA. Electronic address: sharon.nachman@stonybrook.edu.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
authors.affiliation: Levine Children's Hospital at Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Amina
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Indus Hospital, Pakistan.
authors.forename: Farhana
authors.initials: F
authors.lastname: Amanullah
authors.affiliation: Harvard Medical School, Boston, MA, USA.
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Radu
authors.initials: R
authors.lastname: Botgros
authors.affiliation: Médecins Sans Frontières, Access Campaign, Geneva, Switzerland.
authors.forename: Grania
authors.initials: G
authors.lastname: Brigden
authors.affiliation: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Browning
authors.affiliation: TB Alliance, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gardiner
authors.affiliation: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Hafner
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
authors.forename: Anneke
authors.initials: A
authors.lastname: Hesseling
authors.affiliation: Department of Pharmacology and Toxicology, University of the Philippines, Manila, Philippines.
authors.forename: Cleotilde
authors.initials: C
authors.lastname: How
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.affiliation: Treatment Action Group, New York, NY, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Lessem
authors.affiliation: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD, USA.
authors.forename: Mamodikoe
authors.initials: M
authors.lastname: Makhene
authors.affiliation: Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
authors.forename: Nontombi
authors.initials: N
authors.lastname: Mbelle
authors.affiliation: 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.
authors.forename: Ben
authors.initials: B
authors.lastname: Marais
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: McNeeley
authors.affiliation: TB Alliance, New York, NY, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Mendel
authors.affiliation: TB Alliance, New York, NY, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Murray
authors.affiliation: 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.
authors.forename: Eileen
authors.initials: E
authors.lastname: Navarro
authors.affiliation: US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, International Research and Programs Branch, Atlanta, GA, USA.
authors.forename: E Gloria
authors.initials: EG
authors.lastname: Anyalechi
authors.affiliation: 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.
authors.forename: Ariel R
authors.initials: AR
authors.lastname: Porcalla
authors.affiliation: US Agency for International Development, Washington, DC, USA.
authors.forename: Clydette
authors.initials: C
authors.lastname: Powell
authors.affiliation: European Medicines Agency, London, UK.
authors.forename: Mair
authors.initials: M
authors.lastname: Powell
authors.affiliation: New York University School of Medicine, NY, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Rigaud
authors.affiliation: GHESKIO, Port-au-Prince, Haiti.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rouzier
authors.affiliation: Statistical and Data Analysis Center, Center for Biostatistics in AIDS Research and Frontier Science, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Pearl
authors.initials: P
authors.lastname: Samson
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
authors.affiliation: Department of Bioethics, NIH Clinical Center, Bethesda, MD, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Shah
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Starke
authors.affiliation: National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Makerere University Johns Hopkins Research Collaboration, and Mulago National Referral Hospital, Kampala, Uganda.
authors.forename: Eric
authors.initials: E
authors.lastname: Wobudeya
authors.affiliation: Eunice Kennedy Schriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Worrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D032921:Consensus; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents