Objective To review characteristics, methodology and reporting of non-inferiority and equivalence trials in the specific context of paediatrics.
Design PubMed and Cochrane databases were searched (up to September 2016) for non-inferiority/equivalence randomised controlled trials conducted in children published in high-impact-factor journals (>5.0 for general/specialist medical journals; >2.2 for paediatric journals).
Results We found that the statistical hypothesis was inconsistent with the objective in 12 (10%) of the 125 reports included. Non-inferiority (n=98) and equivalence trials (n=27) were mostly used to evaluate interventions with easier administration (45%, n=54/120) and/or better safety profile (34%, n=41/120). All the data needed for targeted sample size recalculation were available for 39 reports (31%). The margin—representing the largest difference between arms that would be clinically acceptable—was reported in 119 (95%), and 44/119 (37%) reported the method used for margin determination. The median sample size was 268 (IQR 125–531). Margins were wider in smaller trials (<125 randomised patients) than in larger trials (p=0.04/p<0.01 for binary/continuous outcomes, respectively). We did not agree with the authors’ conclusions in 11% (11/103) of the reports that provided sufficient information.
Conclusions There is still a need to improve the quality of methodology, reporting and interpretation of non-inferiority/equivalence trials in paediatrics. In particular, the margins were often not justified and the conclusion was often not supported by the design and/or the results. As researchers have to cope with small sample size and with lack of evidence, methods for non-inferiority/equivalence trials need to be used and/or developed in this vulnerable population.
- non-inferiority trials
- equivalence trials
- controlled clinical trials as topic
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Contributors CAu conceptualised and designed the review, designed the data collection instruments, collected the data, carried out the analyses, drafted the initial manuscript, and reviewed and revised the manuscript. SZ, ELR and CAl conceptualised the review, and reviewed and revised the manuscript. GT and RB collected the data and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Full dataset and statistical code are available on request to the corresponding author.
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