Ford D., Turner R., Turkova A., Penazzato M., Musiime V., Bwakura-Dangarembizi M., Violari A., Chabala C., Puthanakit T., Sudjaritruk T., Cressey T. R., Lallemant Marc, Gibb D. M. (2018). Optimizing clinical trial design to maximize evidence generation in pediatric HIV. JAIDS. Journal of Acquired Immune Deficiency Syndromes, 78 (1), p. S40-S48. ISSN 1525-4135.
Titre du document
Optimizing clinical trial design to maximize evidence generation in pediatric HIV
Année de publication
2018
Auteurs
Ford D., Turner R., Turkova A., Penazzato M., Musiime V., Bwakura-Dangarembizi M., Violari A., Chabala C., Puthanakit T., Sudjaritruk T., Cressey T. R., Lallemant Marc, Gibb D. M.
Source
JAIDS. Journal of Acquired Immune Deficiency Syndromes, 2018,
78 (1), p. S40-S48 ISSN 1525-4135
For HIV-infected children, formulation development, pharmacokinetic (PK) data, and evaluation of early toxicity are critical for licensing new antiretroviral drugs; direct evidence of efficacy in children may not be needed if acceptable safety and PK parameters are demonstrated in children. However, it is important to address questions where adult trial data cannot be extrapolated to children. In this fast-moving area, interventions need to be tailored to resource-limited settings where most HIV-infected children live and take account of decreasing numbers of younger HIV-infected children after successful prevention of mother-to-child HIV transmission. Innovative randomized controlled trial (RCT) designs enable several questions relevant to children's treatment and care to be answered within the same study. We reflect on key considerations, and, with examples, discuss the relative merits of different RCT designs for addressing multiple scientific questions including parallel multi-arm RCTs, factorial RCTs, and crossover RCTs. We discuss inclusion of several populations (eg, untreated and pretreated children; children and adults) in "basket" trials; incorporation of secondary randomizations after enrollment and use of nested substudies (particularly PK and formulation acceptability) within large RCTs. We review the literature on trial designs across other disease areas in pediatrics and rare diseases and discuss their relevance for addressing questions relevant to HIV-infected children; we provide an example of a Bayesian trial design in prevention of mother-to-child HIV transmission and consider this approach for future pediatric trials. Finally, we discuss the relevance of these approaches to other areas, in particular, childhood tuberculosis and hepatitis.
Plan de classement
Santé : généralités [050]
;
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010073775]
Identifiant IRD
fdi:010073775
