Clinical trials were missing from regulatory documents of extended-release methylphenidate for ADHD in adults: a case study of public documents

J Clin Epidemiol. 2022 Mar;143:242-253. doi: 10.1016/j.jclinepi.2021.10.027. Epub 2021 Nov 6.

Abstract

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.

Keywords: ADHD; Clinical trials; Drug authorisations; Drug regulatory agencies; Methylphenidate; Psychiatry.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Central Nervous System Stimulants* / therapeutic use
  • Delayed-Action Preparations / therapeutic use
  • Humans
  • Methylphenidate* / therapeutic use
  • Treatment Outcome

Substances

  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Methylphenidate