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Optimizing clinical trial design to maximize evidence generation in pediatric HIV
- Source :
- Journal of Acquired Immune Deficiency Syndromes (1999)
- Publication Year :
- 2018
-
Abstract
- 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 cross-over 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.
- Subjects :
- Adult
medicine.medical_specialty
Pediatric hiv
Drug Compounding
Psychological intervention
MEDLINE
HIV Infections
Disease
030204 cardiovascular system & hematology
Pediatrics
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Humans
Relevance (law)
Medicine
Pharmacology (medical)
030212 general & internal medicine
Child
Intensive care medicine
Hiv transmission
Clinical Trials as Topic
pediatric HIV
business.industry
Clinical study design
HIV
Bayes Theorem
Infectious Disease Transmission, Vertical
clinical trial design
Infectious Diseases
Anti-Retroviral Agents
pediatric clinical trials
Supplement Article
Female
business
Subjects
Details
- Language :
- English
- ISSN :
- 15254135
- Database :
- OpenAIRE
- Journal :
- Journal of Acquired Immune Deficiency Syndromes (1999)
- Accession number :
- edsair.doi.dedup.....ee3017cc4c7687de78553a1a5c6a7116