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Meta-Analysis
. 2019 Mar 30;9(3):e026478.
doi: 10.1136/bmjopen-2018-026478.

Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses

Helle B Krogh  1 , Ole Jakob Storebø  1 , Erlend Faltinsen  1 , Adnan Todorovac  1 , Erica Ydedahl-Jensen  1 , Frederik Løgstrup Magnusson  1 , Mathilde Holmskov  1 , Trine Gerner  1 , Christian Gluud  2 , Erik Simonsen  1
Affiliations
Meta-Analysis

Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses

Helle B Krogh et al. BMJ Open. .

Abstract

Objective: To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).

Design: Secondary analyses of a Cochrane systematic review.

Setting and participants: We searched relevant databases up to March 2015 and included data from parallel and crossover randomised trials assessing children and adolescents up to 18 years with ADHD.

Interventions: Methylphenidate compared with placebo or no-treatment interventions.

Primary and secondary outcomes: The primary outcomes were teacher-rated ADHD symptoms and serious adverse events. The secondary outcomes were non-serious adverse events.

Results: We included 38 parallel trials (n=5111) and 147 crossover trials (n=7134). When comparing methylphenidate with placebo or no-treatment on ADHD symptoms, we found no differences between the end of parallel trials and the first-period from crossover trials (Χ²=1.06, df=1, p=0.30, I²=5.5%). We also found no differences when combining the end of first-period crossover trials with the end of parallel trials and comparing them to the end of last-period crossover trials (Χ²=3.25, df=1, p=0.07, I²=69.2%). We found no differences in serious and non-serious adverse events, and no risk of period and carryover effects. However, only two trials contributed data to the latter analyses.

Conclusions: Both parallel and crossover trials seem suitable for investigating methylphenidate in children and adolescents with ADHD, with comparable estimates on ADHD symptom severity and adverse events. However, parallel trials might still offer ethical and statistical advantages over crossover trials.

Keywords: adhd; attention deficit hyperactivity disorder; crossover trial; methylphenidate; parallel trial.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. ADHD, attention deficit hyperactivity disorder; RCT, randomised clinical trials.
Figure 2
Figure 2
Data from the end of the parallel trials compared with the end of the first period of the crossover trials on the effects of methylphenidate compared with placebo or no intervention on teacher-rated attention deficit hyperactivity disorder symptoms.
Figure 3
Figure 3
Data from the end of the parallel trials plus the end of the first period of the crossover trials compared with data from the end of the last period of the crossover trials on the effects of methylphenidate versus placebo or no intervention on teacher-rated attention deficit hyperactivity disorder symptoms.
Figure 4
Figure 4
Data from the end of the first period compared with data from the end of the last period of crossover trials on the effects of methylphenidate versus placebo or no intervention on teacher-rated attention deficit hyperactivity disorder symptoms.
Figure 5
Figure 5
Data from parallel trials compared with data from end of the last period of crossover trials on serious adverse events.
See this image and copyright information in PMC

References

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