@article{fdi:010073775,
  title = {{O}ptimizing clinical trial design to maximize evidence generation in pediatric {HIV}},
  author = {{F}ord, {D}. and {T}urner, {R}. and {T}urkova, {A}. and {P}enazzato, {M}. and {M}usiime, {V}. and {B}wakura-{D}angarembizi, {M}. and {V}iolari, {A}. and {C}habala, {C}. and {P}uthanakit, {T}. and {S}udjaritruk, {T}. and {C}ressey, {T}. {R}. and {L}allemant, {M}arc and {G}ibb, {D}. {M}.},
  editor = {},
  language = {{ENG}},
  abstract = {{F}or {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. {H}owever, it is important to address questions where adult trial data cannot be extrapolated to children. {I}n 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. {I}nnovative randomized controlled trial ({RCT}) designs enable several questions relevant to children's treatment and care to be answered within the same study. {W}e reflect on key considerations, and, with examples, discuss the relative merits of different {RCT} designs for addressing multiple scientific questions including parallel multi-arm {RCT}s, factorial {RCT}s, and crossover {RCT}s. {W}e 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 {RCT}s. {W}e 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 {B}ayesian trial design in prevention of mother-to-child {HIV} transmission and consider this approach for future pediatric trials. {F}inally, we discuss the relevance of these approaches to other areas, in particular, childhood tuberculosis and hepatitis.},
  keywords = {clinical trial design ; pediatric clinical trials ; pediatric {HIV}},
  booktitle = {},
  journal = {{JAIDS}. {J}ournal of {A}cquired {I}mmune {D}eficiency {S}yndromes},
  volume = {78},
  numero = {1},
  pages = {{S}40--{S}48},
  ISSN = {1525-4135},
  year = {2018},
  DOI = {10.1097/qai.0000000000001748},
  URL = {https://www.documentation.ird.fr/hor/fdi:010073775},
}