Challenges in conducting trials for pediatric tuberculosis meningitis: lessons learned in the field

Post Date: 
2019-10-01
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Publication: 
International Journal of Tuberculosis and Lung Disease
Summary: 

SETTING:
TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.

OBJECTIVE:
To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.

DESIGN:
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 visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.

RESULTS:
Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<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 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.

CONCLUSION:
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 advance treatments for this at-risk population.

Citation: 
Paradkar M, Bell Devaleenal DB, Mvalo T, Arenivas A, Thakur KT, Afrin S, Giridharan P, Selladurai E, Kinikar A, Valve C, Gupta A, Mave V, Dooley KE. Challenges in conducting trials for pediatric tuberculosis meningitis: lessons learned in the field. Int J Tuber Lung Dis. 2019 October 1;23(10): 1082-1089(8). Doi: https://doi.org/10.5588/ijtld.18.0786. PMID: 31627773 .
Collaborators: 
  • University of North Carolina Project-Malawi, Lilongwe, Malawi, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, NC.
  • 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.
  • Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
  • Institute of Child Health and Hospital for Children, Chennai.