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. 2009 Feb;98(2):385-91.
doi: 10.1111/j.1651-2227.2008.01048.x. Epub 2008 Sep 24.

Pitfalls in the design and analysis of paediatric clinical trials: a case of a 'failed' multi-centre study, and potential solutions

Johanna H van der Lee  1 , Michael W T Tanck, Judit Wesseling, Martin Offringa
Affiliations

Pitfalls in the design and analysis of paediatric clinical trials: a case of a 'failed' multi-centre study, and potential solutions

Johanna H van der Lee et al. Acta Paediatr. 2009 Feb.

Abstract

Aim: 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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Double triangular test designed to have 80% power to detect a significant (two-sided α of 0.05) difference of 1.5 days between the two treatments assuming a standard deviation of 2 days with the sample path based on inspection intervals of five patients (a) after 11 inspections (n = 55) in the total patient population; (b) after 7 inspections (n = 35) in the bronchiolitis subgroup; (c) after 7 inspections (n = 35) in the pneumonia subgroup. Figures (b) and (c) represent post-hoc analyses without appropriate correction for multiple testing.
Figure 2
Figure 2
Double triangular test designed to have 80% power to detect a significant (two-sided α of 0.05) difference of 1.5 days between the two treatments assuming a standard deviation of 5.3 days with the sample path based on inspection intervals of five patients after 16 inspections (n = 80) in the total patient population.
See this image and copyright information in PMC

References

    1. Vandenbroucke JP. Case reports in an evidence-based world. J R Soc Med. 1999;92:159–63. - PMC - PubMed
    1. van Woensel JB, van Aalderen WM, de Weerd W, Jansen NJ, van Gestel JP, Markhorst DG, et al. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Thorax. 2003;58:383–7. - PMC - PubMed
    1. Tarnow-Mordi WO, Healy MJ. Distinguishing between “no evidence of effect” and “evidence of no effect” in randomised controlled trials and other comparisons. Arch Dis Child. 1999;80:210–1. - PMC - PubMed
    1. Tasker RC, Gordon I, Kiff K. Time course of severe respiratory syncytial virus infection in mechanically ventilated infants. Acta Paediatr. 2000;89:938–41. - PubMed
    1. Newth CJ. Time course of severe respiratory syncytial virus infection in mechanically ventilated infants. Acta Paediatr. 2000;89:893–5. - PubMed

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