{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:25:28Z","timestamp":1774351528748,"version":"3.50.1"},"reference-count":0,"publisher":"International Union Against Tuberculosis and Lung Disease","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["int j tuberc lung dis"],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:p><jats:bold>SETTING:<\/jats:bold> TBM-KIDS is a phase I\/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.<jats:bold>OBJECTIVE:<\/jats:bold> To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial\n agents in pediatric TBM.<jats:bold>DESIGN:<\/jats:bold> The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review\n visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.<jats:bold>RESULTS:<\/jats:bold> Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for\n eligibility; 21 (&lt;1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection\n of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally.<jats:bold>CONCLUSION:<\/jats:bold>\n Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to\n advance treatments for this at-risk population.<\/jats:p>","DOI":"10.5588\/ijtld.18.0786","type":"journal-article","created":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T04:55:51Z","timestamp":1571460951000},"page":"1082-1089","source":"Crossref","is-referenced-by-count":8,"title":["Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field"],"prefix":"10.5588","volume":"23","author":[{"given":"M.","family":"Paradkar","sequence":"first","affiliation":[{"name":"Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Research Site, Pune"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. B.","family":"Devaleenal","sequence":"additional","affiliation":[{"name":"National Institute for Research in Tuberculosis, Indian Council for Medical Research, Chennai, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Mvalo","sequence":"additional","affiliation":[{"name":"University of North Carolina Project-Malawi, Lilongwe, Malawi, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Arenivas","sequence":"additional","affiliation":[{"name":"The Institute for Rehabilitation and Research Memorial Hermann, Department of Rehabilitation Psychology and Neuropsychology, Houston, TX, Baylor College of Medicine, Department of Physical Medicine and Rehabilitation, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. T.","family":"Thakur","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Afrin","sequence":"additional","affiliation":[{"name":"Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Research Site, Pune"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Giridharan","sequence":"additional","affiliation":[{"name":"National Institute for Research in Tuberculosis, Indian Council for Medical Research, Chennai, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Selladurai","sequence":"additional","affiliation":[{"name":"Institute of Child Health and Hospital for Children, Chennai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Kinikar","sequence":"additional","affiliation":[{"name":"Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Research Site, Pune, BJ Government Medical College, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Valvi","sequence":"additional","affiliation":[{"name":"Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Research Site, Pune, BJ Government Medical College, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Mave","sequence":"additional","affiliation":[{"name":"Byramjee Jeejeebhoy Government Medical College-Johns Hopkins Clinical Research Site, Pune, BJ Government Medical College, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. E.","family":"Dooley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3554","container-title":["The International Journal of Tuberculosis and Lung Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ingentaconnect.com\/content\/iuatld\/ijtld\/2019\/00000023\/00000010\/art00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,19]],"date-time":"2019-10-19T04:55:57Z","timestamp":1571460957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ingentaconnect.com\/content\/10.5588\/ijtld.18.0786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":0,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10,1]]}},"alternative-id":["1027-3719(20191001)23:10L.1082;1-"],"URL":"https:\/\/doi.org\/10.5588\/ijtld.18.0786","relation":{},"ISSN":["1027-3719"],"issn-type":[{"value":"1027-3719","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10,1]]}}}