Pitfalls in the design and analysis of paediatric clinical trials: a case of a 'failed' multi-centre study, and potential solutions.
OBJECTIVE
To increase awareness of possible pitfalls in the design and analysis of a multi-centre randomized clinical trial and to give an overview of alternative study designs and their consequences for power analyses in case of limited availability of trial participants.


METHODS
Investigation of the assumptions in the power calculation and re-analysis of the original data of a 'failed' trial on the effect of dexamethasone on the duration of mechanical ventilation in young children with respiratory syncytial virus infection. Use of 'boundaries approach' is explored using the data from this trial. A comprehensive overview of the various modern solutions for the design of a subsequent trial in this field is given.


RESULTS
Two frequent major deficiencies of trial design and data analysis are reviewed in depth, i.e. too optimistic assumptions for the sample size calculation and failure to adjust for centre effects.


CONCLUSIONS
Critical review of trial assumptions and if necessary sample size recalculation based on an internal pilot by a data monitoring committee is recommended to maximize the probability of obtaining conclusive results.
van der Lee
Johanna H
JH
Department of Paediatric Clinical Epidemiology, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands. j.h.vanderlee@amc.uva.nl
Tanck
Michael W T
MW
Wesseling
Judit
J
Offringa
Martin
M
D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards*; D003907:Dexamethasone / Q000627:therapeutic use; D006801:Humans; D015337:Multicenter Studies as Topic; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D018357:Respiratory Syncytial Virus Infections / Q000628:therapy; D018401:Sample Size; D013997:Time Factors
D003907:Dexamethasone