Clinical trials were missing from regulatory documents of extended-release methylphenidate for ADHD in adults: a case
Kim Boesen1, Karsten Juhl Jørgensen2, Peter C Gøtzsche3
1Meta-Research Innovation Center Berlin (METRIC-B), Berlin Institute of Health at Charité, QUEST Center for Responsible Research, Germany; Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark.
Objectives:
To assess whether drug regulatory agencies decided on applications for extended-release methylphenidate for use in adult ADHD based on select samples of trials.
Study Design And Setting:
Case series of publicly available regulatory documents. We matched an index of extended-release methylphenidate trials for adult ADHD with trials appearing in regulatory documents of extended-release methylphenidate applications. Trials and regulatory documents were identified as part of this systematic review (https://doi.org/10.1002/14651858.CD012857). We sought to identify missing trials in the regulatory documents and to clarify regulatory submission requirements.
Results:
We indexed 18 trials and matched those with 13 drug applications (11 approved, 2 rejected) published by 7 agencies. There were trials missing in 7 (54%) of 13 applications, median 4 trials (range 1-6). The median proportion of missing trial participants was 45% (range 23% - 72%). Regulators seemingly require that all trials must be included in new drug applications, but wording is ambiguous.
Conclusion:
In this sample of extended-release methylphenidate drug applications for adult ADHD, 7 of 13 regulatory decisions were missing entire trials according to public documents, even though regulatory requirements seem to stipulate that all available trials should be included in drug applications.
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