To address concerns regarding the integrity of a clinical trial's findings due to unupdated records on ClinicalTrials.gov.
Approach:
Study Overview: The report discussed is 'Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis: A Randomized Clinical Trial' published in JAMA Psychiatry.
Timeline of Events: The study was registered in April 2018, with significant revisions made in March 2025, before data collection concluded in 2023.
Protocol Modifications: The study team implemented approved protocol modifications from April to December 2018, published a revised protocol in 2021, and included it as a Supplement in the JAMA Psychiatry article.
Key Findings:
Concerns arose about the integrity of the trial's findings due to unupdated ClinicalTrials.gov records. The authors acknowledged the error of not updating the ClinicalTrials.gov entry in real time in their comment on the Online Comments platform.
Interpretation:
The central issue was the lack of timely updates to the ClinicalTrials.gov record, which misled reviewers about the nature of protocol changes.
Limitations:
Some aspects of the rationale for protocol alterations remain debatable, including whether the CATIE study represents an appropriate comparator for research involving first-episode psychosis.
Conclusion:
The omission of real-time updates on ClinicalTrials.gov created an erroneous impression of retrospective alterations to trial elements. The authors acknowledged this error in their comment.
