RT Journal Article
SR Electronic
T1 Important issues in the justification of a control treatment in paediatric drug trials
JF Archives of Disease in Childhood
JO Arch Dis Child
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP 962
OP 967
DO 10.1136/archdischild-2016-310644
VO 101
IS 10
A1 Lauren E Kelly
A1 Elin Haf Davies
A1 Agnes Saint-Raymond
A1 Paolo Tomasi
A1 Martin Offringa
YR 2016
UL http://adc.bmj.com/content/101/10/962.abstract
AB Objective The value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials.Design A literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data.Results Justifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations.Conclusions In order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials.