Document is current

Article History

Received: 24 August 2025

Accepted: 27 January 2026

First Online: 24 March 2026

Declarations

:

: E.C. is self-employed and was paid for her statistical consulting services. C.L. and G.T. are currently self-employed, but at the time the research was conducted, they were employed by the US Food and Drug Administration. E.M. has served as a paid consultant on issues of drug safety to Eli Lilly, i2o, Reata Pharmaceuticals, and Syneos Health and to the Class Plaintiffs of the Xyrem (Sodium Oxybate) Antitrust Litigation, including United Healthcare Services, Inc., Humana Inc., Molina Healthcare, Inc., and Health Care Service Corporation, Inc., and receives compensation for these services. The terms of this arrangement have been reviewed and approved by Loyola University Chicago in accordance with its policy on objectivity in research. C.L. is currently self-employed, but at the time the research was conducted, she was employed by the US Food and Drug Administration. C.L. has served as a paid consultant for UBC and GSK. G.A.T. is employed by Perspective Pharmacovigilance, Inc.,but at the time the research was conducted, she was employed by the US Food and Drug Administration. Elaine Morrato is an editorial board member of Drug Safety . Elaine Morrato was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions.

: The study was approved by the Colorado Multiple Institutional Review Board (protocol #18-1871).

: Not applicable.

: Not applicable.

: REMS reports, REMS data files and Historic REMS information, and data description are publicly available for download directly from the FDA REMS website: .Goals, summary, REMS material, assessment plan, and update history are available for active REMS: .The REMS dashboard offers an interactive web-based tool to visual REMS information: . An XLSX data file with class characteristics and modification categorization are available upon request from the authors.

: The coding dictionary is provided in the supplemental resources. Statistical code is available upon request from the authors.

: All authors meet all four criteria for authorship: (1) substantial contributions to conception or design of the work, or the acquisition, analysis, or interpretation of data for the work; (2) drafting of the work or reviewing it critically for important intellectual content; (3) final approval of the version to be published; and (4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.