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; Ole Jakob Storebø; Erlend Faltinsen; Adnan Todorovac; Erica Ydedahl-Jensen; Frederik Løgstrup Magnusson; Mathilde Holmskov; Trine Gerner; Christian Gluud; Erik Simonsen

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^*, Ole Jakob Storebø, Erlend Faltinsen, Adnan Todorovac, Erica Ydedahl-Jensen, Frederik Løgstrup Magnusson, Mathilde Holmskov, Trine Gerner, Christian Gluud, Erik Simonsen

^*Corresponding author for this work

Department of Clinical Medicine

5 Citations (Scopus)

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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 ( 2;=1.06, df=1, p=0.30, I 2;=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 (? 2;=3.25, df=1, p=0.07, I 2;=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.

Original language	English
Article number	e026478
Journal	BMJ Open
Volume	9
Issue number	3
ISSN	2044-6055
DOIs	https://doi.org/10.1136/bmjopen-2018-026478
Publication status	Published - 1 Mar 2019

Keywords

adhd
attention deficit hyperactivity disorder
crossover trial
methylphenidate
parallel trial

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Krogh, H. B., Storebø, O. J., Faltinsen, E., Todorovac, A., Ydedahl-Jensen, E., Magnusson, F. L., Holmskov, M., Gerner, T., Gluud, C., & Simonsen, E. (2019). Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: A systematic review and meta-analyses. BMJ Open, 9(3), [e026478]. https://doi.org/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. / Krogh, Helle B.; Storebø, Ole Jakob; Faltinsen, Erlend et al.

In: BMJ Open, Vol. 9, No. 3, e026478, 01.03.2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Krogh, HB, Storebø, OJ, Faltinsen, E, Todorovac, A, Ydedahl-Jensen, E, Magnusson, FL, Holmskov, M, Gerner, T, Gluud, C & Simonsen, E 2019, 'Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: A systematic review and meta-analyses', BMJ Open, vol. 9, no. 3, e026478. https://doi.org/10.1136/bmjopen-2018-026478

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title = "Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: A systematic review and meta-analyses",

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 ( 2;=1.06, df=1, p=0.30, I 2;=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 (? 2;=3.25, df=1, p=0.07, I 2;=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.",

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author = "Krogh, {Helle B.} and Storeb{\o}, {Ole Jakob} and Erlend Faltinsen and Adnan Todorovac and Erica Ydedahl-Jensen and Magnusson, {Frederik L{\o}gstrup} and Mathilde Holmskov and Trine Gerner and Christian Gluud and Erik Simonsen",

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doi = "10.1136/bmjopen-2018-026478",

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T1 - Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder

T2 - A systematic review and meta-analyses

AU - Krogh, Helle B.

AU - Storebø, Ole Jakob

AU - Faltinsen, Erlend

AU - Todorovac, Adnan

AU - Ydedahl-Jensen, Erica

AU - Magnusson, Frederik Løgstrup

AU - Holmskov, Mathilde

AU - Gerner, Trine

AU - Gluud, Christian

AU - Simonsen, Erik

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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 ( 2;=1.06, df=1, p=0.30, I 2;=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 (? 2;=3.25, df=1, p=0.07, I 2;=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.

AB - 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 ( 2;=1.06, df=1, p=0.30, I 2;=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 (? 2;=3.25, df=1, p=0.07, I 2;=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.

KW - adhd

KW - attention deficit hyperactivity disorder

KW - crossover trial

KW - methylphenidate

KW - parallel trial

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DO - 10.1136/bmjopen-2018-026478

M3 - Journal article

C2 - 30928951

AN - SCOPUS:85063690530

SN - 2044-6055

VL - 9

JO - BMJ Open

JF - BMJ Open

IS - 3

M1 - e026478

ER -

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

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Keywords

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