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Evaluation of Tuberculosis Diagnostics in Children: 2. Methodological Issues for Conducting and Reporting Research Evaluations of Tuberculosis Diagnostics for Intrathoracic Tuberculosis in Children. Consensus From an Expert Panel

Authors: 
Luis E. Cuevas, Renee Browning, Patrick Bossuyt, Martina Casenghi, Mark F. Cotton, Andrea T. Cruz, Lori E. Dodd, Francis Drobniewski, Marianne Gale, Stephen M. Graham, Malgosia Grzemska, Norbert Heinrich, Anneke C. Hesseling, Robin Huebner, Patrick Jean-Philippe, Sushil Kumar Kabra, Beate Kampmann, Deborah Lewinsohn, Meijuan Li, Christian Lienhardt, Anna M. Mandalakas, Ben J. Marais, Heather J. Menzies, Grace Montepiedra, Charles Mwansambo, Richard Oberhelman, Paul Palumbo, Estelle Russek-Cohen, David E. Shapiro, Betsy Smith, Giselle Soto-Castellares, Jeffrey R. Starke, Soumya Swaminathan, Claire Wingfield and Carol Worrel3
New Reference standards for TB diagnostics in children
As has been highlighted on World TB day, children with TB are an neglected population usually omitted from research in treatment and diagnostics. Accurate diagnosis of Mycobacterium tuberculosis in children has long been difficult and current diagnostic tools available fail to address the problems experienced in diagnosing TB in children.  The development of new tools for children has been hampered by a lack of consensus on case definitions for research purposes. A lack of reference standard contributes to the hesitancy to enrol children in diagnostic research studies. Research into paediatric TB diagnostics is very limited and a consensus on a reference standard should promote further research and ensure that the maximum benefits can be gained from it.
The National Institute of Health sponsored a meeting in June last year “Critical Issues in Paediatric Tuberculosis Diagnostics Research in HIV-Infected and Uninfected Children” bringing together a group of leading paediatric TB experts. The meeting addressed the lack of an agreed  reference standard for diagnostics and a expert consensus was reached on clinical case definitions for intra-thoracic TB diagnosis in children, as well as how to standardize methodological approaches for evaluation of new TB diagnostic tests in children which was published this month in Journal of Infectious Diseases. The published document clearly specifies how to use their definitions to reliably classify a child for research purposes. 
ABSTRACT
Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children.
In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.
TB_MedJourn_JournID_NIHmethodogicalissues_ENG_2012.pdf
Page updated: 3 April 2012
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